Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke

Am J Physiol Cell Physiol. 2019 Feb 1;316(2):C135-C153. doi: 10.1152/ajpcell.00136.2018. Epub 2018 Oct 31.

Abstract

As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junction integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principal mediators and molecular mechanisms involved in BBB disruption is critical for the development of novel therapeutics to treat ischemic stroke. This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke. Specifically, we provide an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.

Keywords: blood-brain barrier; chemokines; cytokines; focal cerebral ischemia; matrix metalloproteinases; middle cerebral artery occlusion; neurovascular injury; oxidative stress; tight junction proteins.

Publication types

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

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / metabolism*
  • Brain Ischemia / immunology
  • Brain Ischemia / metabolism*
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Oxidative Stress / physiology
  • Permeability
  • Stroke / immunology
  • Stroke / metabolism*
  • Tight Junctions / immunology
  • Tight Junctions / metabolism

Substances

  • Inflammation Mediators