Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

Circ Res. 2021 Jun 25;129(1):174-194. doi: 10.1161/CIRCRESAHA.121.318173. Epub 2021 Jun 24.

Abstract

Appropriate vascular function is essential for the maintenance of central nervous system homeostasis and is achieved through virtue of the blood-brain barrier; a specialized structure consisting of endothelial, mural, and astrocytic interactions. While appropriate blood-brain barrier function is typically achieved, the central nervous system vasculature is not infallible and cerebrovascular anomalies, a collective terminology for diverse vascular lesions, are present in meningeal and cerebral vasculature supplying and draining the brain. These conditions, including aneurysmal formation and rupture, arteriovenous malformations, dural arteriovenous fistulas, and cerebral cavernous malformations, and their associated neurological sequelae, are typically managed with neurosurgical or pharmacological approaches. However, increasing evidence implicates interacting roles for inflammatory responses and disrupted central nervous system fluid flow with respect to vascular perturbations. Here, we discuss cerebrovascular anomalies from an immunologic angle and fluid flow perspective. We describe immune contributions, both common and distinct, to the formation and progression of diverse cerebrovascular anomalies. Next, we summarize how cerebrovascular anomalies precipitate diverse neurological sequelae, including seizures, hydrocephalus, and cognitive effects and possible contributions through the recently identified lymphatic and glymphatic systems. Finally, we speculate on and provide testable hypotheses for novel nonsurgical therapeutic approaches for alleviating neurological impairments arising from cerebrovascular anomalies, with a particular emphasis on the normalization of fluid flow and alleviation of inflammation through manipulations of the lymphatic and glymphatic central nervous system clearance pathways.

Keywords: blood-brain barrier; central nervous system; inflammation; meninges.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Brain / blood supply*
  • Central Nervous System Vascular Malformations* / cerebrospinal fluid
  • Central Nervous System Vascular Malformations* / genetics
  • Central Nervous System Vascular Malformations* / immunology
  • Central Nervous System Vascular Malformations* / therapy
  • Cerebral Arteries / abnormalities*
  • Cerebral Arteries / immunology
  • Cerebral Arteries / metabolism
  • Cerebral Veins / abnormalities*
  • Cerebral Veins / immunology
  • Cerebral Veins / metabolism
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Immunity, Innate*
  • Phenotype
  • Risk Factors