Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke.

The blood-brain barrier (BBB), also known as the neurovascular unit, 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 junctions integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principle 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, vascular endothelial growth factor, as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.