Involvement of caveolin-1 in neurovascular unit remodeling after stroke: Effects on neovascularization and astrogliosis

J Cereb Blood Flow Metab. 2020 Jan;40(1):163-176. doi: 10.1177/0271678X18806893. Epub 2018 Oct 24.

Abstract

Complex cellular and molecular events occur in the neurovascular unit after stroke, such as blood-brain barrier (BBB) dysfunction and inflammation that contribute to neuronal death, neurological deterioration and mortality. Caveolin-1 (Cav-1) has distinct physiological functions such as caveolae formation associated with endocytosis and transcytosis as well as in signaling pathways. Cav-1 has been proposed to be involved in BBB dysfunction after brain injury; however, its precise role is poorly understood. The goal of this study was to characterize the expression and effect of Cav-1 deletion on outcome in the first week in a transient Middle Cerebral Artery Occlusion stroke model. We found increased Cav-1 expression in new blood vessels in the lesion and in reactive astrocytes in the peri-lesion areas. In Cav-1 KO mice, the lesion volume was larger and the behavioral outcome worse than in WT mice. Cav-1 KO mice exhibited reduced neovascularization and modified astrogliosis, without formation of a proper glial scar around the lesion at three days post injury, coinciding with aggravated outcomes. Altogether, these results point towards a potential protective role of endogenous Cav-1 in the first days after ischemia by promoting neovascularization, astrogliosis and scar formation.

Keywords: Caveolin-1; astrogliosis; ischemic stroke; neovascularization; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology
  • Blood-Brain Barrier / pathology
  • Caveolin 1 / metabolism
  • Caveolin 1 / pharmacology
  • Caveolin 1 / physiology*
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery
  • Mice
  • Mice, Knockout
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / pathology*
  • Neuronal Plasticity / physiology*
  • Stroke / physiopathology*

Substances

  • Cav1 protein, mouse
  • Caveolin 1