Journal: J Cereb Blood Flow Metab

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<div><h4>Group 2 innate lymphoid cells suppress neuroinflammation and brain injury following intracerebral hemorrhage.</h4><i>Liu M, Wang D, Xu L, Pan Y, ... Li M, Liu Q</i><br /><AbstractText>Intracerebral hemorrhage (ICH) mobilizes circulating leukocytes that contribute to neuroinflammation and neural injury. However, little is known about the endogenous regulatory immune mechanisms to restrict neuroinflammation following ICH. We examined the role of group 2 innate lymphoid cells (ILC2) that are a specialized subset of innate immune modulators in a mouse model of ICH. We found accumulation of ILC2 in the brain following acute ICH and a concomitant increase of ILC2 within the peripheral lymph nodes. Depletion of ILC2 exacerbated neurodeficits and brain edema after ICH in male and female mice. This aggravated ICH injury was accompanied by augmented microglia activity and leukocyte infiltration. In contrast, expansion of ILC2 using IL-33 led to reduced ICH injury, microglia activity and leukocyte infiltration. Notably, elimination of microglia using a colony stimulating factor 1 receptor inhibitor diminished the exacerbation of ICH injury induced by depletion of ILC2. Brain-infiltrating ILC2 had upregulation of IL-13 after ICH. Results from <i>in vitro</i> assays revealed that ILC2 suppressed thrombin-induced inflammatory activity in microglia-like BV2 cells. Thus, our findings demonstrate that ILC2 suppress neuroinflammation and acute ICH injury.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 07 Nov 2023:271678X231208168; epub ahead of print</small></div>
Liu M, Wang D, Xu L, Pan Y, ... Li M, Liu Q
J Cereb Blood Flow Metab: 07 Nov 2023:271678X231208168; epub ahead of print | PMID: 37933727
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<div><h4>Post-stroke brain can be protected by modulating the lncRNA FosDT.</h4><i>Mehta SL, Chelluboina B, Morris-Blanco KC, Bathula S, ... Davis CK, Vemuganti R</i><br /><AbstractText>We previously showed that knockdown or deletion of Fos downstream transcript (FosDT; a stroke-induced brain-specific long noncoding RNA) is neuroprotective. We presently tested the therapeutic potential of FosDT siRNA in rodents subjected to transient middle cerebral artery occlusion (MCAO) using the Stroke Treatment Academic Industry Roundtable criteria, including sex, age, species, and comorbidity. FosDT siRNA (IV) given at 30 min of reperfusion significantly improved motor function recovery (rotarod test, beam walk test, and adhesive removal test) and reduced infarct size in adult and aged spontaneously hypertensive rats of both sexes. FosDT siRNA administered in a delayed fashion (3.5 h of reperfusion following 1 h transient MCAO) also significantly improved motor function recovery and decreased infarct volume. Furthermore, FosDT siRNA enhanced post-stroke functional recovery in normal and diabetic mice. Mechanistically, FosDT triggered post-ischemic neuronal damage via the transcription factor REST as REST siRNA mitigated the enhanced functional outcome in FosDT<sup>-/-</sup> rats. Additionally, NF-κB regulated FosDT expression as NF-κB inhibitor BAY 11-7082 significantly decreased post-ischemic FosDT induction. Thus, FosDT is a promising target with a favorable therapeutic window to mitigate secondary brain damage and facilitate recovery after stroke regardless of sex, age, species, and comorbidity.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 07 Nov 2023:271678X231212378; epub ahead of print</small></div>
Mehta SL, Chelluboina B, Morris-Blanco KC, Bathula S, ... Davis CK, Vemuganti R
J Cereb Blood Flow Metab: 07 Nov 2023:271678X231212378; epub ahead of print | PMID: 37933735
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<div><h4>Treatment with the vascular endothelial growth factor-A antibody, bevacizumab, has sex-specific effects in a rat model of mild traumatic brain injury.</h4><i>Sun M, Baker TL, Wilson CT, Brady RD, ... McDonald SJ, Shultz SR</i><br /><AbstractText>Mild traumatic brain injury (mTBI) involves damage to the cerebrovascular system. Vascular endothelial growth factor-A (VEGF-A) is an important modulator of vascular health and VEGF-A promotes the brain\'s ability to recover after more severe forms of brain injury; however, the role of VEGF-A in mTBI remains poorly understood. Bevacizumab (BEV) is a monoclonal antibody that binds to VEGF-A and neutralises its actions. To better understand the role of VEGF-A in mTBI recovery, this study examined how BEV treatment affected outcomes in rats given a mTBI. Adult Sprague-Dawley rats were assigned to sham-injury + vehicle treatment (VEH), sham-injury + BEV treatment, mTBI + VEH treatment, mTBI + BEV treatment groups. Treatment was administered intracerebroventricularly via a cannula beginning at the time of injury and continuing until the end of the study. Rats underwent behavioral testing after injury and were euthanized on day 11. In both females and males, BEV had a negative impact on cognitive function. mTBI and BEV treatment increased the expression of inflammatory markers in females. In males, BEV treatment altered markers related to hypoxia and vascular health. These novel findings of sex-specific responses to BEV and mTBI provide important insights into the role of VEGF-A in mTBI.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 07 Nov 2023:271678X231212377; epub ahead of print</small></div>
Sun M, Baker TL, Wilson CT, Brady RD, ... McDonald SJ, Shultz SR
J Cereb Blood Flow Metab: 07 Nov 2023:271678X231212377; epub ahead of print | PMID: 37933736
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<div><h4>Static autoregulation in humans.</h4><i>Wang Y, Payne SJ</i><br /><AbstractText>The process by which cerebral blood flow (CBF) remains approximately constant in response to short-term variations in arterial blood pressure (ABP) is known as cerebral autoregulation. This classic view, that it remains constant over a wide range of ABP, has however been challenged by a growing number of studies. To provide an updated understanding of the static cerebral pressure-flow relationship and to characterise the autoregulation curve more rigorously, we conducted a comprehensive literature research. Results were based on 143 studies in healthy individuals aged 18 to 65 years. The mean sensitivities of CBF to changes in ABP were found to be 1.47 ± 0.71%/% for decreased ABP and 0.37 ± 0.38%/% for increased ABP. The significant difference in CBF directional sensitivity suggests that cerebral autoregulation appears to be more effective in buffering increases in ABP than decreases in ABP. Regression analysis of absolute CBF and ABP identified an autoregulatory plateau of approximately 20 mmHg (ABP between 80 and 100 mmHg), which is much smaller than the widely accepted classical view. Age and sex were found to have no effect on autoregulation strength. This data-driven approach provides a quantitative method of analysing static autoregulation that can be easily updated as more experimental data become available.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 07 Nov 2023:271678X231210430; epub ahead of print</small></div>
Wang Y, Payne SJ
J Cereb Blood Flow Metab: 07 Nov 2023:271678X231210430; epub ahead of print | PMID: 37933742
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<div><h4>Blood-brain barrier disruption imaging in postoperative cerebral hyperperfusion syndrome using DCE-MRI.</h4><i>Lee K, Yoo RE, Cho WS, Choi SH, ... Kang HS, Kim JE</i><br /><AbstractText>Little has been reported about the association between cerebral hyperperfusion syndrome (CHS) and blood-brain barrier (BBB) disruption in human. We aimed to investigate the changes in permeability after bypass surgery in cerebrovascular steno-occlusive diseases using dynamic contrast-enhanced MRI (DCE-MRI) and to demonstrate the association between CHS and BBB disruption. This retrospective study included 36 patients (21 hemispheres in 18 CHS patients and 20 hemispheres in 18 controls) who underwent combined bypass surgery for moyamoya and atherosclerotic steno-occlusive diseases. DCE-MRI and arterial spin labeling perfusion-weighted imaging (ASL-PWI) were obtained at the baseline, postoperative state, and discharge. Perfusion and permeability parameters were calculated at the MCA territory (CBF<sub>(territorial)</sub>, K<sup>trans</sup><sub>(territorial)</sub>, V<sub>p(territorial)</sub>) and focal perianastomotic area (CBF<sub>(focal)</sub>, K<sup>trans</sup><sub>(focal)</sub>, V<sub>p(focal)</sub>) of operated hemispheres. As compared with the baseline, both CBF<sub>(territorial)</sub> and CBF<sub>(focal)</sub> increased in the postoperative period and decreased at discharge, corresponding well to symptoms in the CHS group. V<sub>p(focal)</sub> was lower in the postoperative period and at discharge, as compared with the baseline. In the control group, no parameters significantly differed among the three points. In conclusion, V<sub>p</sub> at the focal perianastomotic area significantly decreased in patients with CHS during the postoperative period. BBB disruption may be implicated in the development of CHS after bypass surgery.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Nov 2023:271678X231212173; epub ahead of print</small></div>
Lee K, Yoo RE, Cho WS, Choi SH, ... Kang HS, Kim JE
J Cereb Blood Flow Metab: 01 Nov 2023:271678X231212173; epub ahead of print | PMID: 37910856
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<div><h4>Cerebral hemodynamics and stroke risks in symptomatic intracranial atherosclerotic stenosis with internal versus cortical borderzone infarcts: A computational fluid dynamics study.</h4><i>Li S, Tian X, Ip B, Feng X, ... Leng X, Leung TW</i><br /><AbstractText>There may be different mechanisms underlying internal (IBZ) and cortical (CBZ) borderzone infarcts in intracranial atherosclerotic stenosis. In 84 patients with symptomatic, 50-99% atherosclerotic stenosis of M1 middle cerebral artery (MCA-M1) with acute borderzone infarcts in diffusion-weighted imaging, we classified the infarct patterns as isolated IBZ (n = 37), isolated CBZ (n = 31), and IBZ+CBZ (n = 16) infarcts. CT angiography-based computational fluid dynamics models were constructed to quantify translesional, post-stenotic to pre-stenotic pressure ratio (PR) in the MCA-M1 lesion. Those with IBZ infarcts were more likely to have a low PR (indicating impaired antegrade flow across the lesion) than those without (p = 0.012), and those with CBZ infarcts were more likely to have coexisting small cortical infarcts (indicating possible embolism) than those without (p = 0.004). In those with isolated IBZ or CBZ infarcts, low PR was independently associated with isolated IBZ infarcts (adjusted odds ratio = 4.223; p = 0.026). These two groups may also have different trajectories in the stroke risks under current medical treatment regimen, with a higher risk of same-territory ischemic stroke recurrence within 3 months in patients with isolated IBZ infarcts than isolated CBZ infarcts (17.9% versus 0.0%; log-rank p = 0.023), but similar risks later in 1 year.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 28 Oct 2023:271678X231211449; epub ahead of print</small></div>
Li S, Tian X, Ip B, Feng X, ... Leng X, Leung TW
J Cereb Blood Flow Metab: 28 Oct 2023:271678X231211449; epub ahead of print | PMID: 37898104
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<div><h4>Transnasal cooling: New prospect of selective hypothermia in acute ischemic stroke.</h4><i>Chen X, Xu S, Li M, Wu D, Ji X</i><br /><AbstractText>Rapid and selective therapeutic hypothermia is a promising neuroprotective method for acute ischemic stroke. A recent study developed a simple but efficient technique of transnasal cooling, in which air at ambient temperature was passed through standard nasal cannula to induce evaporative cooling of the brain. Selective brain temperature decrease was achieved within 25 minutes in piglets. It is a major step forward to initiate early brain cooling. However, it is still necessary to devise a more comprehensive strategy to enhance the benefits of selective brain cooling in the era of effective reperfusion.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 28 Oct 2023:271678X231211726; epub ahead of print</small></div>
Chen X, Xu S, Li M, Wu D, Ji X
J Cereb Blood Flow Metab: 28 Oct 2023:271678X231211726; epub ahead of print | PMID: 37898106
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<div><h4>Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction.</h4><i>Zhou K, Tan Y, Zhang G, Li J, ... Zeng J, Zhang J</i><br /><AbstractText>Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin receptor homology domain protein (SARM1) can induce Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in <i>Sarm1</i><sup>-/-</sup> mice after photothrombotic infarction. Compared with wild-type mice, <i>Sarm1</i><sup>-/-</sup> mice exhibited unaltered infarct volume; however, there were markedly reduced neuronal death and gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of <i>Sarm1</i><sup>-/-</sup> mice after cerebral infarction. Thalamic <i>Sarm1</i> re-expression in <i>Sarm1</i><sup>-/-</sup> mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor 3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through rapamycin treatment aggravated post-stroke neuronal death and gliosis in <i>Sarm1</i><sup>-/-</sup> mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 28 Oct 2023:271678X231210694; epub ahead of print</small></div>
Zhou K, Tan Y, Zhang G, Li J, ... Zeng J, Zhang J
J Cereb Blood Flow Metab: 28 Oct 2023:271678X231210694; epub ahead of print | PMID: 37898107
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<div><h4>Global, regional, and national burden of ischemic stroke attributed to high low-density lipoprotein cholesterol, 1990-2019:A decomposition analysis and age-period-cohort analysis.</h4><i>Zhang J, Zhu S, Liu C, Hu Y, ... Zhang Y, Hong Y</i><br /><AbstractText>High levels of low-density lipoprotein cholesterol (LDL-C) have been associated with an augmented mortality of ischemic stroke. The yearly deaths and mortality data of IS-hLDL-C were derived from the global burden of disease 2019 dataset. The joinpoint, age-period-cohort and decomposition analysis were utilized to evaluate the long-term patterns in the disease burden of IS-hLDL-C, and the effects of population growth and aging. Globally, in 2019, 0.61 million ischemic stroke-related deaths were attributable to high LDL-C, with the highest death burden in the high-middle socio-demographic index (SDI) region. From 1990 to 2019, the age-standardized death rate (ASDR) for IS-hLDL-C exhibited a downward trend, with an average annual percentage change of -1.69 [95% confidence interval: -1.90, -1.48)]. The fastest decreasing trends in ASDR were experienced in the high SDI region. In 119 (58.33%) countries, aging increased the disease burden of hLDL-IS, and population growth increased the disease burden of IS-hLDL-C in 163 (79.90%) countries. The trend in disease burden of IS-hLDL-C exhibited variation across countries and regions, particularly in territories with high to middle high SDI. Aging in upper to middle-income countries and population growth in low to middle-income countries further offset endeavors to reduce the burden of ischemic stroke deaths.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 27 Oct 2023:271678X231211448; epub ahead of print</small></div>
Zhang J, Zhu S, Liu C, Hu Y, ... Zhang Y, Hong Y
J Cereb Blood Flow Metab: 27 Oct 2023:271678X231211448; epub ahead of print | PMID: 37891501
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<div><h4>Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [C]raclopride and positron emission tomography.</h4><i>Johansson J, Ericsson M, Axelsson J, Bjerkén SA, Virel A, Karalija N</i><br /><AbstractText>Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [<sup>11</sup>C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [<sup>11</sup>C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [<sup>11</sup>C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [<sup>11</sup>C]raclopride-PET can be employed to detect such spatiotemporal differences.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 26 Oct 2023:271678X231210128; epub ahead of print</small></div>
Johansson J, Ericsson M, Axelsson J, Bjerkén SA, Virel A, Karalija N
J Cereb Blood Flow Metab: 26 Oct 2023:271678X231210128; epub ahead of print | PMID: 37882727
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<div><h4>Changes in cardiac-driven perivascular fluid movement around the MCA in a pharmacological model of acute hypertension detected with non-invasive MRI.</h4><i>Evans PG, Sajic M, Yu Y, Harrison IF, ... Stuckey DJ, Wells JA</i><br /><AbstractText>Perivascular spaces mediate a complex interaction between cerebrospinal fluid and brain tissue that may be an important pathway for solute waste clearance. Their structural or functional derangement may contribute to the development of age-related neurogenerative conditions. Here, we employed a non-invasive low <i>b</i><b>-</b>value diffusion-weighted ECG-gated MRI method to capture perivascular fluid movement around the middle cerebral artery of the anaesthetised rat brain. Using this method, we show that such MRI estimates of perivascular fluid movement directionality are highly sensitive to the cardiac cycle. We then show that these measures of fluid movement directionality are decreased in the angiotensin-II pharmacological model of acute hypertension, with an associated dampening of vessel pulsatility. This translational MRI method may, therefore, be useful to monitor derangement of perivascular fluid movement associated with cardiovascular pathologies, such as hypertension, in order to further our understanding of perivascular function in neurology.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 24 Oct 2023:271678X231209641; epub ahead of print</small></div>
Evans PG, Sajic M, Yu Y, Harrison IF, ... Stuckey DJ, Wells JA
J Cereb Blood Flow Metab: 24 Oct 2023:271678X231209641; epub ahead of print | PMID: 37873754
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<div><h4>Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.</h4><i>Franx BA, van Tilborg GA, Taha A, Bobi J, ... Dijkhuizen RM, CONTRAST consortium</i><br /><AbstractText>Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats (N = 60) were subjected to 45-/90-min filament-induced transient middle cerebral artery occlusion. Diffusion, T<sub>2</sub>- and perfusion-weighted MRI at occlusion, 0.5 h and four days after recanalization, enabled tracking of tissue fate, and relative regional cerebral blood flow (rrCBF) and -volume (rrCBV). Lesion areas were parcellated into core, salvageable tissue and delayed injury, verified by histology. Recanalization resulted in acute-to-subacute lesion volume reductions, most apparently in females (n = 19). Hyperacute normo-to-hyperperfusion in the post-ischemic lesion augmented towards day four, particularly in males (n = 23). Tissue suffering delayed injury contained higher ratios of hypoperfused voxels early after recanalization. Regressed against acute-to-subacute lesion volume change, increased rrCBF associated with lesion growth, but increased rrCBV with lesion reduction. Similar relationships were detected for behavioral outcome. Post-ischemic hyperperfusion may develop differentially in males and females, and can be beneficial or detrimental to disease outcome, depending on which perfusion parameter is used as explanatory variable.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 24 Oct 2023:271678X231208993; epub ahead of print</small></div>
Franx BA, van Tilborg GA, Taha A, Bobi J, ... Dijkhuizen RM, CONTRAST consortium
J Cereb Blood Flow Metab: 24 Oct 2023:271678X231208993; epub ahead of print | PMID: 37873758
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<div><h4>Commentary to brain-wide continuous functional ultrasound imaging for real-time monitoring of hemodynamics during ischemic stroke.</h4><i>Nowak TS, Farr TD</i><br /><AbstractText>Functional ultrasound (FUS) has emerged as a novel imaging method to reliably assess relative cerebral blood volume (rCBV) and infer perfusion, with good spatiotemporal resolution. Brunner and colleagues provide what appears to be its first application to characterize peri-infarct spreading depolarizations (SDs) in experimental stroke through recording of transient hyperemic events. They also report incomplete overlap between acute perfusion deficits and subsequent infarct distribution, specifically noting a rostral expansion to involve penumbral territory from which propagating depolarizations had preferentially originated. This observation would not be straightforward using other methodologies. Other strengths and limitations of the study are considered.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 23 Oct 2023:271678X231207182; epub ahead of print</small></div>
Nowak TS, Farr TD
J Cereb Blood Flow Metab: 23 Oct 2023:271678X231207182; epub ahead of print | PMID: 37871620
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<div><h4>Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.</h4><i>Zhang S, Zhao J, Sha WM, Zhang XP, ... Bartlett PF, Hou ST</i><br /><AbstractText>Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 23 Oct 2023:271678X231209607; epub ahead of print</small></div>
Zhang S, Zhao J, Sha WM, Zhang XP, ... Bartlett PF, Hou ST
J Cereb Blood Flow Metab: 23 Oct 2023:271678X231209607; epub ahead of print | PMID: 37871622
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<div><h4>Incidence, severity and impact on functional outcome of persistent hypoperfusion despite large-vessel recanalization, a potential marker of impaired microvascular reperfusion: Systematic review of the clinical literature.</h4><i>Schiphorst AT, Turc G, Hassen WB, Oppenheim C, Baron JC</i><br /><AbstractText>The reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among clinical studies, possibly due to differences in i) definition of complete recanalization, with only recent Thrombolysis in Cerebral Infarction (TICI) grading schemes allowing distinction between complete (TICI3) and partial recanalization with distal occlusions (TICI2c); ii) operational definition of IMR; and iii) consideration of potential alternative causes for hypoperfusion, notably carotid stenosis, re-occlusion and post-thrombectomy hemorrhage. We performed a systematic review to identify clinical studies that carried out brain perfusion imaging within 72 hrs post-thrombectomy for anterior circulation stroke and reported hypoperfusion rates separately for TICI3 and TICI2c grades. Authors were contacted if this data was missing. We identified eight eligible articles, altogether reporting 636 patients. The incidence of IMR after complete recanalization (i.e., TICI3) tended to decrease with the number of considered alternative causes of hypoperfusion: range 12.5-42.9%, 0-31.6% and 0-9.1% in articles that considered none, two or all three causes, respectively. No study reported the impact of IMR on functional outcome separately for TICI-3 patients. Based on this systematic review, IMR in true complete recanalization appears relatively rare, and reported incidence highly depends on definition used and consideration of confounding factors.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 23 Oct 2023:271678X231209069; epub ahead of print</small></div>
Schiphorst AT, Turc G, Hassen WB, Oppenheim C, Baron JC
J Cereb Blood Flow Metab: 23 Oct 2023:271678X231209069; epub ahead of print | PMID: 37871624
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<div><h4>\"No-reflow\" phenomenon in acute ischemic stroke.</h4><i>Zhang Y, Jiang M, Gao Y, Zhao W, ... Wang W, Ji X</i><br /><AbstractText>Acute ischemic stroke (AIS) afflicts millions of individuals worldwide. Despite the advancements in thrombolysis and thrombectomy facilitating proximal large artery recanalization, the resultant distal hypoperfusion, referred to \"no-reflow\" phenomenon, often impedes the neurological function restoration in patients. Over half a century of scientific inquiry has validated the existence of cerebral \"no-reflow\" in both animal models and human subjects. Furthermore, the correlation between \"no-reflow\" and adverse clinical outcomes underscores the necessity to address this phenomenon as a pivotal strategy for enhancing AIS prognoses. The underlying mechanisms of \"no-reflow\" are multifaceted, encompassing the formation of microemboli, microvascular compression and contraction. Moreover, a myriad of complex mechanisms warrant further investigation. Insights gleaned from mechanistic exploration have prompted advancements in \"no-reflow\" treatment, including microthrombosis therapy, which has demonstrated clinical efficacy in improving patient prognoses. The stagnation in current \"no-reflow\" diagnostic methods imposes limitations on the timely application of combined therapy on \"no-reflow\" post-recanalization. This narrative review will traverse the historical journey of the \"no-reflow\" phenomenon, delve into its underpinnings in AIS, and elucidate potential therapeutic and diagnostic strategies. Our aim is to equip readers with a swift comprehension of the \"no-reflow\" phenomenon and highlight critical points for future research endeavors.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 19 Oct 2023:271678X231208476; epub ahead of print</small></div>
Zhang Y, Jiang M, Gao Y, Zhao W, ... Wang W, Ji X
J Cereb Blood Flow Metab: 19 Oct 2023:271678X231208476; epub ahead of print | PMID: 37855115
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<div><h4>The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.</h4><i>Dhillon SK, Lear CA, Davidson JO, Magawa S, Gunn AJ, Bennet L</i><br /><AbstractText>Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 12 Oct 2023:271678X231197380; epub ahead of print</small></div>
Dhillon SK, Lear CA, Davidson JO, Magawa S, Gunn AJ, Bennet L
J Cereb Blood Flow Metab: 12 Oct 2023:271678X231197380; epub ahead of print | PMID: 37824725
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<div><h4>Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.</h4><i>Rebelos E, Latva-Rasku A, Koskensalo K, Pekkarinen L, ... Ferrannini E, Nuutila P</i><br /><AbstractText>The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (<sup>1</sup>H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG-PET)) was also performed in a subset of subjects during clamp. In <i>dataset A,</i> 48 participants were studied during fasting with brain <sup>1</sup>H-MRS, while in <i>dataset B</i> 21 participants underwent paired brain <sup>1</sup>H-MRS acquisitions under fasting and clamp conditions. In <i>dataset C</i> 16 subjects underwent brain <sup>18</sup>F-FDG-PET and <sup>1</sup>H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 12 Oct 2023:271678X231207114; epub ahead of print</small></div>
Rebelos E, Latva-Rasku A, Koskensalo K, Pekkarinen L, ... Ferrannini E, Nuutila P
J Cereb Blood Flow Metab: 12 Oct 2023:271678X231207114; epub ahead of print | PMID: 37824728
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Abstract
<div><h4>Effect and mechanisms of resveratrol in animal models of ischemic stroke: A systematic review and Bayesian meta-analysis.</h4><i>López-Morales MA, Castelló-Ruiz M, Burguete MC, Hervás D, Pérez-Pinzón MA, Salom JB</i><br /><AbstractText>Resveratrol (RSV) holds promise as cerebroprotective treatment in cerebral ischemia. This systematic review aims to assess the effects and mechanisms of RSV in animal models of ischemic stroke. We searched Medline, Embase and Web of Science to identify 75 and 57 eligible rodent studies for qualitative and quantitative syntheses, respectively. Range of evidence met 10 of 13 STAIR criteria. Median (Q1, Q3) quality score was 7 (5, 8) on the CAMARADES 15-item checklist. Bayesian meta-analysis showed SMD estimates (95% CI) favoring RSV: infarct size (-1.72 [-2.03; -1.41]), edema size (-1.61 [-2.24; -0.98]), BBB impairment (-1.85 [-2.54; -1.19]), neurofunctional impairment (-1.60 [-1.92; -1.29]), and motor performance (1.39 [0.64; 2.08]); and less probably neuronal survival (0.63 [-1.40; 2.48]) and apoptosis (-0.96 [-2.87; 1.02]). Species (rat vs mouse) was associated to a larger benefit. Sensitivity analyses confirmed robustness of the estimates. Reduction of oxidative stress, inflammation, and apoptosis underlie these effects. Our results quantitatively state the beneficial effects of RSV on structural and functional outcomes in rodent stroke models, update the evidence on the mechanisms of action, and provide an exhaustive list of targeted signaling pathways. Current evidence highlights the need for conducting further high-quality preclinical research to better inform clinical research.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 06 Oct 2023:271678X231206236; epub ahead of print</small></div>
López-Morales MA, Castelló-Ruiz M, Burguete MC, Hervás D, Pérez-Pinzón MA, Salom JB
J Cereb Blood Flow Metab: 06 Oct 2023:271678X231206236; epub ahead of print | PMID: 37802493
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<div><h4>Large-scale functional network connectivity mediates the associations between lipids metabolism and cognition in type 2 diabetes.</h4><i>Zhang W, Fu L, Bi Y, Liu J, ... Cheng H, Zhang B</i><br /><AbstractText>Type 2 diabetes (T2D) is associated with dyslipidemia and mild cognitive impairment. This study investigated the relationships between serum lipids metabolism, cognition, and functional connectivity (FC) within and between brain networks in T2D patients. The study included 102 T2D patients and 45 healthy controls who underwent functional magnetic resonance imaging, lipid profile tests, and cognitive assessments. Thirteen functional networks were identified using independent component analysis. The statistical analyses included multivariate analysis of covariance, partial correlation, canonical correlation, and mediation analyses. We found widely reduced between-network FCs in T2D, especially between the ventral sensorimotor network (SMN) and dorsal attention network (DAN) (p = 0.001) and between the ventral SMN and lateral visual network (VN) (p < 0.001). Moreover, lower between-network FCs were correlated with worse serum lipids metabolism and poorer cognitive performance (all p < 0.05). Importantly, between-network FCs mediated the relationship between lipid metabolism and cognition (β = -0.3136, 95% CI: -0.7660, -0.0186). Within-network analyses revealed altered FCs within the anterior default mode network, DAN, and lateral VN, each positively correlated with global cognition (all p < 0.01). Our results suggest the potential of improving cognitive function by regulating serum lipids in individuals with T2D.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 05 Oct 2023:271678X231204426; epub ahead of print</small></div>
Zhang W, Fu L, Bi Y, Liu J, ... Cheng H, Zhang B
J Cereb Blood Flow Metab: 05 Oct 2023:271678X231204426; epub ahead of print | PMID: 37795619
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<div><h4>[F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging.</h4><i>Knyzeliene A, MacAskill MG, Alcaide-Corral CJ, Morgan TE, ... Sutherland A, Tavares AA</i><br /><AbstractText>Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [<sup>18</sup>F]LW223, in mice and specifically assess its volume of non-displaceable binding (<i>V<sub>ND</sub></i>) in brain as well as investigate the use of simplified analysis approaches for quantification of [<sup>18</sup>F]LW223 PET data. Adult male mice were injected with [<sup>18</sup>F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate <i>V<sub>ND</sub></i> of [<sup>18</sup>F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (<i>SUV</i>) and apparent volume of distribution (<i>V<sub>Tapp</sub></i>), were investigated. [<sup>18</sup>F]LW223 had low <i>V<sub>ND</sub></i> in the brain (<10% of total binding) and low radiometabolism (∼15-20%). The 2-tissue compartment model provided the best fit for [<sup>18</sup>F]LW223 PET data, although its correlation with <i>SUV<sub>90-120min</sub></i> or <i>V<sub>Tapp</sub></i> allowed for [<sup>18</sup>F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [<sup>18</sup>F]LW223 has the required properties to become a successful TSPO PET radiotracer.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 05 Oct 2023:271678X231205661; epub ahead of print</small></div>
Knyzeliene A, MacAskill MG, Alcaide-Corral CJ, Morgan TE, ... Sutherland A, Tavares AA
J Cereb Blood Flow Metab: 05 Oct 2023:271678X231205661; epub ahead of print | PMID: 37795635
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Abstract
<div><h4>Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.</h4><i>Jia J, Xu S, Hu J, Gan Y, ... Zhang M, Xu Y</i><br /><AbstractText>Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Growth arrest specific protein 6 (Gas6) clears myelin debris, which is hypothesized to promote white matter integrity in experimental stroke models. By the middle cerebral artery occlusion (MCAO) stroke model, we observed that Gas6 reduced infarcted volume and behavior deficits 4 weeks after MCAO. Compared with control mice, Gas6-treatment mice represented higher FA values in the ipsilateral external capsules by MRI DTI scan. The SMI32/MBP ratio of the ipsilateral cortex and striatum was profoundly alleviated by Gas6 administration. Gas6-treatment group manifested thicker myelin sheaths than the control group by electron microscopy. We observed that Gas6 mainly promoted OPC maturation, which was closely related to microglia. Mechanically, Gas6 accelerated microglia-mediated myelin debris clearance and cholesterol transport protein expression (<i>abca1</i>, <i>abcg1</i>, <i>apoc1</i>, <i>apoe</i>) <i>in vivo</i> and <i>in vitro</i>, accordingly less myelin debris and lipid deposited in Gas6 treated stroke mice. HX531 (RXR inhibitor) administration mitigated the functions of Gas6 in speeding up debris clearance and cholesterol transport protein expression. Generally, we concluded that Gas6 cleared myelin debris and promoted cholesterol transportation protein expression through activating RXR, which could be one critical mechanism contributing to white matter repair after stroke.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 05 Oct 2023:271678X231205078; epub ahead of print</small></div>
Jia J, Xu S, Hu J, Gan Y, ... Zhang M, Xu Y
J Cereb Blood Flow Metab: 05 Oct 2023:271678X231205078; epub ahead of print | PMID: 37794790
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Abstract
<div><h4>Antihypertensives in dementia: Good or bad for the brain?</h4><i>Beishon L, Haunton VJ, Panerai RB</i><br /><AbstractText>Hypertension is associated with both ageing and dementia. Despite this, optimal blood pressure targets in dementia remain unclear. Both high and low blood pressure are associated with poorer cognition. Changes in vascular physiology in dementia may increase the vulnerability of the brain to hypoperfusion associated with antihypertensives. We discuss the potential risks of antihypertensives in the context of altered cerebral haemodynamics, and evidence from antihypertensive trials in dementia. We suggest that individualised blood pressure targets should be the focus for antihypertensive therapy in dementia, rather than strict control to uniform targets extrapolated from trials in cognitively healthy individuals.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Oct 2023; 43:1800-1802</small></div>
Beishon L, Haunton VJ, Panerai RB
J Cereb Blood Flow Metab: 01 Oct 2023; 43:1800-1802 | PMID: 36284494
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<div><h4>Similarity between structural and proxy estimates of brain connectivity.</h4><i>Lizarraga A, Ripp I, Sala A, Shi K, ... Koch K, Yakushev I</i><br /><AbstractText>Functional magnetic resonance and diffusion weighted imaging have so far made a major contribution to delineation of the brain connectome at the macroscale. While functional connectivity (FC) was shown to be related to structural connectivity (SC) to a certain degree, their spatial overlap is unknown. Even less clear are relations of SC with estimates of connectivity from inter-subject covariance of regional F18-fluorodeoxyglucose uptake (FDG<sub>cov</sub>) and grey matter volume (GMV<sub>cov</sub>). Here, we asked to what extent SC underlies three proxy estimates of brain connectivity: FC, FDG<sub>cov</sub> and GMV<sub>cov</sub>. Simultaneous PET/MR acquisitions were performed in 56 healthy middle-aged individuals. Similarity between four networks was assessed using Spearman correlation and convergence ratio (CR), a measure of spatial overlap. Spearman correlation coefficient was 0.27 for SC-FC, 0.40 for SC-FDG<sub>cov</sub>, and 0.15 for SC-GMV<sub>cov</sub>. Mean CRs were 51% for SC-FC, 48% for SC-FDG<sub>cov</sub>, and 37% for SC-GMV<sub>cov</sub>. These results proved to be reproducible and robust against image processing steps. In sum, we found a relevant similarity of SC with FC and FDG<sub>cov</sub>, while GMV<sub>cov</sub> consistently showed the weakest similarity. These findings indicate that white matter tracts underlie FDG<sub>cov</sub> to a similar degree as FC, supporting FDG<sub>cov</sub> as estimate of functional brain connectivity.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 29 Sep 2023:271678X231204769; epub ahead of print</small></div>
Lizarraga A, Ripp I, Sala A, Shi K, ... Koch K, Yakushev I
J Cereb Blood Flow Metab: 29 Sep 2023:271678X231204769; epub ahead of print | PMID: 37773727
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Abstract
<div><h4>Randomized placebo-controlled trial of CL2020, an allogenic muse cell-based product, in subacute ischemic stroke.</h4><i>Niizuma K, Osawa SI, Endo H, Izumi SI, ... Iwano M, Tominaga T</i><br /><AbstractText>Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 27 Sep 2023:271678X231202594; epub ahead of print</small></div>
Niizuma K, Osawa SI, Endo H, Izumi SI, ... Iwano M, Tominaga T
J Cereb Blood Flow Metab: 27 Sep 2023:271678X231202594; epub ahead of print | PMID: 37756573
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Abstract
<div><h4>The effect of hypercapnia on the directional sensitivity of dynamic cerebral autoregulation and the influence of age and sex.</h4><i>Panerai RB, Davies A, Clough RH, Beishon LC, Robinson TG, Minhas JS</i><br /><AbstractText>The cerebral circulation responds differently to increases in mean arterial pressure (MAP), compared to reductions in MAP. We tested the hypothesis that this directional sensitivity is reduced by hypercapnia. Retrospective analysis of 104 healthy subjects (46 male (44%), age range 19-74 years), with five minute recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), non-invasive MAP (Finometer) and end-tidal CO<sub>2</sub> (capnography) at rest, during both poikilocapnia and hypercapnia (5% CO<sub>2</sub> breathing in air) produced MCAv step responses allowing estimation of the classical Autoregulation Index (ARI<sub>ORIG</sub>), and corresponding values for both positive (ARI<sub>+D</sub>) and negative (ARI<sub>-D</sub>) changes in MAP. Hypercapnia led to marked reductions in ARI<sub>ORIG</sub>, ARI<sub>+D</sub> and ARI<sub>-D</sub> (p < 0.0001, all cases). Females had a lower value of ARI<sub>ORIG</sub> compared to males (p = 0.030) at poikilocapnia (4.44 ± 1.74 vs 4.74 ± 1.48) and hypercapnia (2.44 ± 1.93 vs 3.33 ± 1.61). The strength of directional sensitivity (ARI<sub>+D</sub>-ARI<sub>-D</sub>) was not influenced by hypercapnia (p = 0.46), sex (p = 0.76) or age (p = 0.61). During poikilocapnia, ARI<sub>+D</sub> decreased with age in females (p = 0.027), but not in males. Directional sensitivity was not affected by hypercapnia, suggesting that its origins are more likely to be inherent to the mechanics of vascular smooth muscle than to myogenic pathways.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 25 Sep 2023:271678X231203475; epub ahead of print</small></div>
Panerai RB, Davies A, Clough RH, Beishon LC, Robinson TG, Minhas JS
J Cereb Blood Flow Metab: 25 Sep 2023:271678X231203475; epub ahead of print | PMID: 37747437
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<div><h4>A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules.</h4><i>Shaked I, Foo C, Mächler P, Liu R, ... Friedman B, Kleinfeld D</i><br /><AbstractText>How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active <i>D</i>-glucose into healthy mice. The observed real-time responses to laser-induced disruption include rapid serum extravasation, platelet aggregation, and neutrophil recruitment. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, and by a nitric oxide donor. As a control, vessel thrombo-inflammation is significantly reduced in mice injected with metabolically inert <i>L</i>-glucose. Venules in mice with diabetes show a similar response to laser-induced disruption and damage is reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies between transient metabolic and physical vascular perturbations and can reveal new aspects of brain pathophysiology.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 22 Sep 2023:271678X231203023; epub ahead of print</small></div>
Shaked I, Foo C, Mächler P, Liu R, ... Friedman B, Kleinfeld D
J Cereb Blood Flow Metab: 22 Sep 2023:271678X231203023; epub ahead of print | PMID: 37737093
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<div><h4>Penumbral cooling in ischemic stroke with intraarterial, intravenous or active conductive head cooling: A thermal modeling study.</h4><i>Diprose WK, Rao A, Ghate K, Dyer Z, ... Almekhlafi M, Barber PA</i><br /><AbstractText>In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and <i>in vivo</i> brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 21 Sep 2023:271678X231203025; epub ahead of print</small></div>
Diprose WK, Rao A, Ghate K, Dyer Z, ... Almekhlafi M, Barber PA
J Cereb Blood Flow Metab: 21 Sep 2023:271678X231203025; epub ahead of print | PMID: 37734834
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<div><h4>[C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier.</h4><i>Mairinger S, Leterrier S, Filip T, Löbsch M, ... Langer O, Wanek T</i><br /><AbstractText>The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [<sup>11</sup>C]metoclopramide to measure decreased cerebral P-gp function, we performed [<sup>11</sup>C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous <i>Abcb1a/b</i><sup>(+/-)</sup> and homozygous <i>Abcb1a/b</i><sup>(-/-)</sup> mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry. Brain uptake of [<sup>11</sup>C]metoclopramide was expressed as the area under the brain time-activity curve (AUC<sub>brain</sub>) and compared with data previously obtained with (<i>R</i>)-[<sup>11</sup>C]verapamil and [<sup>11</sup>C]<i>N</i>-desmethyl-loperamide. <i>Abcb1a/b</i><sup>(+/-)</sup> mice had intermediate P-gp expression compared to wild-type and <i>Abcb1a/b</i><sup>(-/-)</sup> mice. In baseline scans, all three radiotracers were able to discriminate <i>Abcb1a/b</i><sup>(-/-)</sup> from wild-type mice (2.5- to 4.6-fold increased AUC<sub>brain</sub>, p ≤ 0.0001). However, only [<sup>11</sup>C]metoclopramide could discriminate <i>Abcb1a/b</i><sup>(+/-)</sup> from wild-type mice (1.46-fold increased AUC<sub>brain</sub>, p ≤ 0.001). After partial P-gp inhibition, differences in [<sup>11</sup>C]metoclopramide AUC<sub>brain</sub> between <i>Abcb1a/b</i><sup>(+/-)</sup> and wild-type mice (1.39-fold, p ≤ 0.001) remained comparable to baseline. There was a negative correlation between baseline [<sup>11</sup>C]metoclopramide AUC<sub>brain</sub> and <i>ex-vivo</i>-measured P-gp immunofluorescence (r = <i>-</i>0.9875, p ≤ 0.0001). Our data suggest that [<sup>11</sup>C]metoclopramide is a sensitive radiotracer to measure moderate, but (patho-)physiologically relevant decreases in cerebral P-gp function without the need to co-administer a P-gp inhibitor.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 20 Sep 2023:271678X231202336; epub ahead of print</small></div>
Mairinger S, Leterrier S, Filip T, Löbsch M, ... Langer O, Wanek T
J Cereb Blood Flow Metab: 20 Sep 2023:271678X231202336; epub ahead of print | PMID: 37728771
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<div><h4>Whisker-evoked neurovascular coupling is preserved during hypoglycemia in mouse cortical arterioles and capillaries.</h4><i>Nippert AR, Chiang PP, Newman EA</i><br /><AbstractText>Hypoglycemia is a serious complication of insulin treatment of diabetes that can lead to coma and death. Neurovascular coupling, which mediates increased local blood flow in response to neuronal activity, increases glucose availability to active neurons. This mechanism could be essential for neuronal health during hypoglycemia, when total glucose supplies are low. Previous studies suggest, however, that neurovascular coupling (a transient blood flow increase in response to an increase in neuronal activity) may be reduced during hypoglycemia. Such a reduction in blood flow increase would exacerbate the effects of hypoglycemia, depriving active neurons of glucose. We have reexamined the effects of hypoglycemia on neurovascular coupling by simultaneously monitoring neuronal and vascular responses to whisker stimulation in the awake mouse somatosensory cortex. We find that neurovascular coupling at both penetrating arterioles and at 2nd order capillaries did not change significantly during insulin-induced hypoglycemia compared to euglycemia. In addition, we show that the basal diameter of both arterioles and capillaries increases during hypoglycemia (10.3 and 9.7% increases, respectively). Our results demonstrate that both neurovascular coupling and basal increases in vessel diameter are active mechanisms which help to maintain an adequate supply of glucose to the brain during hypoglycemia.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 20 Sep 2023:271678X231201241; epub ahead of print</small></div>
Nippert AR, Chiang PP, Newman EA
J Cereb Blood Flow Metab: 20 Sep 2023:271678X231201241; epub ahead of print | PMID: 37728791
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<div><h4>Multimodal imaging of the role of hyperglycemia following experimental subarachnoid hemorrhage.</h4><i>Joya A, Plaza-García S, Padro D, Aguado L, ... Justicia C, Martín A</i><br /><AbstractText>Hyperglycemia has been linked to worsening outcomes after subarachnoid hemorrhage (SAH). Nevertheless, the mechanisms involved in the pathogenesis of SAH have been scarcely evaluated so far. The role of hyperglycemia was assessed in an experimental model of SAH by T<sub>2</sub> weighted, dynamic contrast-enhanced magnetic resonance imaging (T<sub>2</sub>W and DCE-MRI), [<sup>18</sup>F]BR-351 PET imaging and immunohistochemistry. Measures included the volume of bleeding, the extent of cerebral infarction and brain edema, blood brain barrier disruption (BBBd), neutrophil infiltration and matrix metalloprotease (MMP) activation. The neurofunctional outcome, neurodegeneration and myelinization were also investigated. The induction of hyperglycemia increased mortality, the size of the ischemic lesion, brain edema, neurodegeneration and worsened neurological outcome during the first 3 days after SAH in rats. In addition, these results show for the first time the exacerbating effect of hyperglycemia on <i>in vivo</i> MMP activation, Intercellular Adhesion Molecule 1 (ICAM-1) expression and neutrophil infiltration together with increased BBBd, bleeding volume and fibrinogen accumulation at days 1 and 3 after SAH. Notably, these data provide valuable insight into the detrimental effect of hyperglycemia on early BBB damage mediated by neutrophil infiltration and MMP activation that could explain the worse prognosis in SAH.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 20 Sep 2023:271678X231197946; epub ahead of print</small></div>
Joya A, Plaza-García S, Padro D, Aguado L, ... Justicia C, Martín A
J Cereb Blood Flow Metab: 20 Sep 2023:271678X231197946; epub ahead of print | PMID: 37728631
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<div><h4>Increased task-relevant fMRI responsiveness in comatose cardiac arrest patients is associated with improved neurologic outcomes.</h4><i>Dhakal K, Rosenthal ES, Kulpanowski AM, Dodelson JA, ... Greer DM, Wu O</i><br /><AbstractText>Early prediction of the recovery of consciousness in comatose cardiac arrest patients remains challenging. We prospectively studied task-relevant fMRI responses in 19 comatose cardiac arrest patients and five healthy controls to assess the fMRI\'s utility for neuroprognostication. Tasks involved instrumental music listening, forward and backward language listening, and motor imagery. Task-specific reference images were created from group-level fMRI responses from the healthy controls. Dice scores measured the overlap of individual subject-level fMRI responses with the reference images. Task-relevant responsiveness index (Rindex) was calculated as the maximum Dice score across the four tasks. Correlation analyses showed that increased Dice scores were significantly associated with arousal recovery (<i>P < 0.05</i>) and emergence from the minimally conscious state (EMCS) by one year (<i>P < 0.001</i>) for all tasks except motor imagery. Greater Rindex was significantly correlated with improved arousal recovery (P = 0.002) and consciousness (P = 0.001). For patients who survived to discharge (<i>n = 6</i>), the Rindex\'s sensitivity was 75% for predicting EMCS (n = 4). Task-based fMRI holds promise for detecting covert consciousness in comatose cardiac arrest patients, but further studies are needed to confirm these findings. Caution is necessary when interpreting the absence of task-relevant fMRI responses as a surrogate for inevitable poor neurological prognosis.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 20 Sep 2023:271678X231197392; epub ahead of print</small></div>
Dhakal K, Rosenthal ES, Kulpanowski AM, Dodelson JA, ... Greer DM, Wu O
J Cereb Blood Flow Metab: 20 Sep 2023:271678X231197392; epub ahead of print | PMID: 37728641
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<div><h4>Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal.</h4><i>Scott MR, Edwards NC, Properzi MJ, Jacobs HI, ... Schultz AP, Buckley RF</i><br /><AbstractText>Clinically normal females exhibit higher <sup>18</sup>F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or partial volume effects (PVEs). 343 clinically normal participants (female = 58%; mean[SD]=73.8[8.5] years) and 55 patients with mild cognitive impairment (female = 38%; mean[SD] = 76.9[7.3] years) underwent cross-sectional FTP-PET. We parcellated extracerebral FreeSurfer areas based on proximity to cortical ROIs. Sex differences in cortical tau were then estimated after accounting for local extracerebral retention. We simulated PVE by convolving group-level standardized uptake value ratio means in each ROI with 6 mm Gaussian kernels and compared the sexes across ROIs post-smoothing. Widespread sex differences in extracerebral retention were observed. Although attenuating sex differences in cortical tau-PET signal, covarying for extracerebral retention did not impact the largest sex differences in tau-PET signal. Differences in PVE were observed in both female and male directions with no clear sex-specific bias. Our findings suggest that sex differences in FTP are not solely attributed to off-target extracerebral retention or PVE, consistent with the notion that sex differences in medial temporal and neocortical tau are biologically driven. Future work should investigate sex differences in regional cerebral blood flow kinetics and longitudinal tau-PET.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 20 Sep 2023:271678X231196978; epub ahead of print</small></div>
Scott MR, Edwards NC, Properzi MJ, Jacobs HI, ... Schultz AP, Buckley RF
J Cereb Blood Flow Metab: 20 Sep 2023:271678X231196978; epub ahead of print | PMID: 37728659
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Abstract
<div><h4>Multifaceted neural and vascular pathologies after pediatric mild traumatic brain injury.</h4><i>Mayer AR, Dodd AB, Robertson-Benta CR, Zotev V, ... Tarawneh R, Sapien RE</i><br /><AbstractText>Dynamic changes in neurodevelopment and cognitive functioning occur during adolescence, including a switch from reactive to more proactive forms of cognitive control, including response inhibition. Pediatric mild traumatic brain injury (pmTBI) affects these cognitions immediately post-injury, but the role of vascular versus neural injury in cognitive dysfunction remains debated. This study consecutively recruited 214 sub-acute pmTBI (8-18 years) and age/sex-matched healthy controls (HC; N = 186), with high retention rates (>80%) at four months post-injury. Multimodal imaging (functional MRI during response inhibition, cerebral blood flow and cerebrovascular reactivity) assessed for pathologies within the neurovascular unit. Patients exhibited increased errors of commission and hypoactivation of motor circuitry during processing of probes. Evidence of increased/delayed cerebrovascular reactivity within motor circuitry during hypercapnia was present along with normal perfusion. Neither age-at-injury nor post-concussive symptom load were strongly associated with imaging abnormalities. Collectively, mild cognitive impairments and clinical symptoms may continue up to four months post-injury. Prolonged dysfunction within the neurovascular unit was observed during proactive response inhibition, with preliminary evidence that neural and pure vascular trauma are statistically independent. These findings suggest pmTBI is characterized by multifaceted pathologies during the sub-acute injury stage that persist several months post-injury.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 19 Sep 2023:271678X231197188; epub ahead of print</small></div>
Mayer AR, Dodd AB, Robertson-Benta CR, Zotev V, ... Tarawneh R, Sapien RE
J Cereb Blood Flow Metab: 19 Sep 2023:271678X231197188; epub ahead of print | PMID: 37724718
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Abstract
<div><h4>Characterizing cerebrospinal fluid mobility using heavily T2-weighted 3D fast spin echo (FSE) imaging with improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) preparation.</h4><i>Ran L, He Y, Zhu J, Long F, ... Wang W, Wang M</i><br /><AbstractText>Cerebrospinal fluid (CSF) flow patterns and their relationship with arterial pulsation can depict the function of glymphatic system (GS). We propose an improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) prepared heavily T2-weighted 3D FSE (iMDDSDE-HT2) magnetic resonance imaging (MRI) method to noninvasively assess the mobility (MO) of CSF distributed in the ventricles and perivascular spaces (PVS). This method could obtain 3D high resolution (1 mm isotropic) imaging of CSF MO with full brain coverage within five min and distinguish the CSF MO across different pulse phases using a peripheral pulse unit (PPU). The MO curves had the largest amplitude value in the PVS of middle cerebral artery (11.11 × 10<sup>-9</sup> m<sup>2/s</sup>) and the largest amplitude growth rate in the posterior cerebral artery (189%). The average coefficient of variations (CVs) in non-pulse trigger and pulse phase 1 and 3 were 0.11, 0.10 and 0.09 respectively. The MO in older healthy participants was lower compared to the young participants, and the MO in cerebral major artery stenosis patients with acute ischemia stroke (AIS) were lower compared to those without AIS in several ventriclar ROIs (P < 0.05). This sequence is a clinically feasible method to effectively evaluate CSF flow patterns in human brain.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 17 Sep 2023:271678X231194863; epub ahead of print</small></div>
Ran L, He Y, Zhu J, Long F, ... Wang W, Wang M
J Cereb Blood Flow Metab: 17 Sep 2023:271678X231194863; epub ahead of print | PMID: 37717175
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Abstract
<div><h4>Microstructural white matter integrity in relation to vascular reactivity in Dutch-type hereditary cerebral amyloid angiopathy.</h4><i>Schipper MR, Vlegels N, van Harten TW, Rasing I, ... van Walderveen MA, Wermer MJ</i><br /><AbstractText>Cerebral Amyloid Angiopathy (CAA) is characterized by cerebrovascular amyloid-β accumulation leading to hallmark cortical MRI markers, such as vascular reactivity, but white matter is also affected. By studying the relationship in different disease stages of Dutch-type CAA (D-CAA), we tested the relation between vascular reactivity and microstructural white matter integrity loss. In a cross-sectional study in D-CAA, 3 T MRI was performed with Blood-Oxygen-Level-Dependent (BOLD) fMRI upon visual activation to assess vascular reactivity and diffusion tensor imaging to assess microstructural white matter integrity through Peak Width of Skeletonized Mean Diffusivity (PSMD). We assessed the relationship between BOLD parameters - amplitude, time-to-peak (TTP), and time-to-baseline (TTB) - and PSMD, with linear and quadratic regression modeling. In total, 25 participants were included (15/10 pre-symptomatic/symptomatic; mean age 36/59 y). A lowered BOLD amplitude (unstandardized β = 0.64, 95%CI [0.10, 1.18], <i>p </i>= 0.02, Adjusted R<sup>2</sup> = 0.48), was quadratically associated with increased PSMD levels. A delayed BOLD response, with prolonged TTP (β = 8.34 × 10<sup>-6</sup>, 95%CI [1.84 × 10<sup>-6</sup>, 1.48 × 10<sup>-5</sup>], <i>p </i>= 0.02, Adj. R<sup>2</sup> = 0.25) and TTB (β = 6.57 × 10<sup>-6</sup>, 95%CI [1.92 × 10<sup>-6</sup>, 1.12 × 10<sup>-5</sup>], <i>p </i>= 0.008, Adj. R<sup>2</sup> = 0.29), was linearly associated with increased PSMD. In D-CAA subjects, predominantly in the symptomatic stage, impaired cerebrovascular reactivity is related to microstructural white matter integrity loss. Future longitudinal studies are needed to investigate whether this relation is causal.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 14 Sep 2023:271678X231200425; epub ahead of print</small></div>
Schipper MR, Vlegels N, van Harten TW, Rasing I, ... van Walderveen MA, Wermer MJ
J Cereb Blood Flow Metab: 14 Sep 2023:271678X231200425; epub ahead of print | PMID: 37708241
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Abstract
<div><h4>Lower middle cerebral artery blood velocity during low-volume high-intensity interval exercise in chronic stroke.</h4><i>Whitaker AA, Waghmare S, Montgomery RN, Aaron SE, ... Vidoni ED, Billinger SA</i><br /><AbstractText>High-intensity interval training (HIIE) may present unique challenges to the cerebrovascular system in individuals post-stroke. We hypothesized lower middle cerebral artery blood velocity (MCAv) in individuals post-stroke: 1) during 10 minutes of HIIE, 2) immediately following HIIE, and 3) 30 minutes after HIIE, compared to age- and sex-matched controls (CON). We used a recumbent stepper submaximal exercise test to determine workloads for high-intensity and active recovery. Our low volume HIIE protocol consisted of 1-minute intervals for 10 minutes. During HIIE, we measured MCAv, mean arterial pressure (MAP), heart rate (HR), and end tidal carbon dioxide (P<sub>ET</sub>CO<sub>2</sub>). We assessed carotid-femoral pulse wave velocity as a measure of arterial stiffness. Fifty participants completed the study (25 post-stroke, 76% ischemic, 32% moderate disability). Individuals post-stroke had lower MCAv during HIIE compared to CON (p = 0.03), which remained 30 minutes after HIIE. Individuals post-stroke had greater arterial stiffness (p = 0.01) which was moderately associated with a smaller MCAv responsiveness during HIIE (r = -0.44). No differences were found for MAP, HR, and P<sub>ET</sub>CO<sub>2</sub>. This study suggests individuals post-stroke had a lower MCAv during HIIE compared to their peers, which remained during recovery up to 30 minutes. Arterial stiffness may contribute to the lower cerebrovascular responsiveness post-stroke.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 14 Sep 2023:271678X231201472; epub ahead of print</small></div>
Whitaker AA, Waghmare S, Montgomery RN, Aaron SE, ... Vidoni ED, Billinger SA
J Cereb Blood Flow Metab: 14 Sep 2023:271678X231201472; epub ahead of print | PMID: 37708242
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Abstract
<div><h4>More severe initial manifestations and worse short-term functional outcome of intracerebral hemorrhage in the plateau than in the plain.</h4><i>Wang X, Sun H, Wang X, Lan J, ... Cui L, Ji X</i><br /><AbstractText>Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. However, studies on ICH at high altitude are insufficient. We aimed to compare the initial manifestations, imaging features and short-term functional outcomes of ICH at different altitudes, and further explore the effect of altitude on the severity and prognosis of ICH. We retrospectively recruited ICH patients from January 2018 to July 2021 from two centers at different altitudes in China. Information regarding to clinical manifestations, neuroimages, and functional outcomes at discharge were collected and analyzed. Association between altitude and initial severity, neuroimages, and short-term prognosis of ICH were also investigated. A total of 724 patients with 400 lowlanders and 324 highlanders were enrolled. Compared with patients from the plain, those at high altitude were characterized by more severe preliminary manifestations (<i>P < </i>0.0001), larger hematoma volume (<i>P < </i>0.001) and poorer short-term functional outcome (<i>P < </i>0.0001). High altitude was independently associated with dependency at discharge (adjusted <i>P = </i>0.024), in-hospital mortality (adjusted <i>P = </i>0.049) and gastrointestinal hemorrhage incidence (adjusted <i>P = </i>0.017). ICH patients from high altitude suffered from more serious initial manifestations and worse short-term functional outcome than lowlanders. Control of blood pressure, oxygen supplementation and inhibition of inflammation may be critical for ICH at high altitude.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 14 Sep 2023:271678X231201088; epub ahead of print</small></div>
Wang X, Sun H, Wang X, Lan J, ... Cui L, Ji X
J Cereb Blood Flow Metab: 14 Sep 2023:271678X231201088; epub ahead of print | PMID: 37708253
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Abstract
<div><h4>Expansion of plasma MicroRNAs over the first month following human stroke.</h4><i>Edwardson MA, Shivapurkar N, Li J, Khan M, ... Fan R, Dromerick AW</i><br /><AbstractText>Few have characterized miRNA expression during the transition from injury to neural repair and secondary neurodegeneration following stroke in humans. We compared expression of 754 miRNAs from plasma samples collected 5, 15, and 30 days post-ischemic stroke from a discovery cohort (n = 55) and 15-days post-ischemic stroke from a validation cohort (n = 48) to healthy control samples (n = 55 and 48 respectively) matched for age, sex, race and cardiovascular comorbidities using qRT-PCR. Eight miRNAs remained significantly altered across all time points in both cohorts including many described in acute stroke. The number of significantly dysregulated miRNAs more than doubled from post-stroke day 5 (19 miRNAs) to days 15 (50 miRNAs) and 30 (57 miRNAs). Twelve brain-enriched miRNAs were significantly altered at one or more time points (decreased expression, stroke versus controls: miR-107; increased expression: miR-99-5p, miR-127-3p, miR-128-3p, miR-181a-3p, miR-181a-5p, miR-382-5p, miR-433-3p, miR-491-5p, miR-495-3p, miR-874-3p, and miR-941). Many brain-enriched miRNAs were associated with apoptosis over the first month post-stroke whereas other miRNAs suggested a transition to synapse regulation and neuronal protection by day 30. These findings suggest that a program of decreased cellular proliferation may last at least 30 days post-stroke, and points to specific miRNAs that could contribute to neural repair in humans.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 11 Sep 2023:271678X231196982; epub ahead of print</small></div>
Edwardson MA, Shivapurkar N, Li J, Khan M, ... Fan R, Dromerick AW
J Cereb Blood Flow Metab: 11 Sep 2023:271678X231196982; epub ahead of print | PMID: 37694957
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<div><h4>Evaluating infusion methods and simplified quantification of synaptic density with [C]UCB-J and [F]SynVesT-1 PET.</h4><i>Asch RH, Naganawa M, Nabulsi N, Huan Y, Esterlis I, Carson RE</i><br /><AbstractText>For some positron emission tomography studies, radiotracer is administered as bolus plus continuous infusion (B/I) to achieve a state of equilibrium. This approach can reduce scanning time and simplify data analysis; however, the method must be validated and optimized for each tracer. This study aimed to validate a B/I method for <i>in vivo</i> quantification of synaptic density using radiotracers which target the synaptic vesicle glycoprotein 2 A: [<sup>11</sup>C]UCB-J and [<sup>18</sup>F]SynVesT-1. Observed mean standardized uptake values (SUV) in target tissue relative to that in plasma (<i>C</i><sub>T</sub>/<i>C</i><sub>P</sub>) or a reference tissue (SUVR-1) were calculated for 30-minute intervals across 120 or 150-minute dynamic scans and compared against one-tissue compartment (1TC) model estimates of volume of distribution (<i>V</i><sub>T</sub>) and binding potential (<i>BP</i><sub>ND</sub>), respectively. We were unable to reliably achieve a state of equilibrium with [<sup>11</sup>C]UCB-J, and all 30-minute windows yielded overly large bias and/or variability for <i>C</i><sub>T</sub>/<i>C</i><sub>P</sub> and SUVR-1. With [<sup>18</sup>F]SynVesT-1, a 30-minute scan 90-120 minutes post-injection yielded <i>C</i><sub>T</sub>/<i>C</i><sub>P</sub> and SUVR-1 values that estimated their respective kinetic parameter with sufficient accuracy and precision (within 7<mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:mo>±</mml:mo></mml:math>6%) . This B/I approach allows a clinically feasible scan at equilibrium with potentially better accuracy than a static scan SUVR following a bolus injection.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 05 Sep 2023:271678X231200423; epub ahead of print</small></div>
Asch RH, Naganawa M, Nabulsi N, Huan Y, Esterlis I, Carson RE
J Cereb Blood Flow Metab: 05 Sep 2023:271678X231200423; epub ahead of print | PMID: 37669455
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Abstract
<div><h4>Prediction of early neurological deterioration in acute ischemic stroke patients treated with intravenous thrombolysis.</h4><i>Tian T, Wang L, Xu J, Jia Y, ... Li S, Min L</i><br /><AbstractText>A proportion of acute ischemic stroke (AIS) patients suffer from early neurological deterioration (END) within 24 hours following intravenous thrombolysis (IVT), which greatly increases the risk of poor prognosis of these patients. Therefore, we aimed to explore the predictors of early neurological deterioration of ischemic origin (END<sub>i</sub>) in AIS patients after IVT and develop a nomogram prediction model. This study collected 244 AIS patients with post-thrombolysis END<sub>i</sub> as the derivation cohort and 155 patients as the validation cohort. To establish a nomogram prediction model, risk factors were identified by multivariate logistic regression analysis. The results showed that neutrophil to lymphocyte ratio (NLR) (OR 2.616, 95% CI 1.640-4.175, P < 0.001), mean platelet volume (MPV) (OR 3.334, 95% CI 1.351-8.299, P = 0.009), body mass index (BMI) (OR 1.979, 95% CI 1.285-3.048, P = 0.002) and atrial fibrillation (AF) (OR 8.012, 95% CI 1.341-47.873, P = 0.023) were significantly associated with END<sub>i</sub>. The area under the curve of the prediction model constructed from the above four factors was 0.981 (95% CI 0.961-1.000) and the calibration curve was close to the ideal diagonal line. Therefore, this nomogram prediction model exhibited good discrimination and calibration power and might be a reliable and easy-to-use tool to predict post-thrombolysis END<sub>i</sub> in AIS patients.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 05 Sep 2023:271678X231200117; epub ahead of print</small></div>
Tian T, Wang L, Xu J, Jia Y, ... Li S, Min L
J Cereb Blood Flow Metab: 05 Sep 2023:271678X231200117; epub ahead of print | PMID: 37668997
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<div><h4>: Transfer function analysis of dynamic cerebral autoregulation: To band or not to band?</h4><i>Liu J, Simpson DM, Panerai RB</i><br /><AbstractText>Transfer function analysis (TFA) is the most frequently adopted method for assessing dynamic cerebral autoregulation (CA) with continuously recorded arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). Conventionally, values of autoregulatory metrics (e.g., gain and phase) derived from TFA are averaged within three frequency bands separated by cut-off frequencies at 0.07 Hz and 0.20 Hz, respectively, to represent the efficiency of dynamic CA. However, this is of increasing concerns, as there remains no solid evidence for choosing these specific cut-off frequencies, and the rigid adoption of these bands can stifle further developments in TFA of dynamic CA. In this \'Point-Counterpoint\' mini-review, we provide evidence against the fixed banding, indicate possible alternatives, and call for awareness of the risk of the \'one-size-fits-all\' banding becoming dogmatic. We conclude that we need to remain open to the multiple possibilities offered by TFA to realize its full potential in studies of human dynamic CA.</AbstractText><br /><br /><br /><br /><small>J Cereb Blood Flow Metab: 01 Sep 2023; 43:1628-1630</small></div>
Liu J, Simpson DM, Panerai RB
J Cereb Blood Flow Metab: 01 Sep 2023; 43:1628-1630 | PMID: 35510667
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This program is still in alpha version.