Blood-brain barrier in stroke: Pathophysiological mechanisms and treatment approach

Abstract

The blood-brain barrier (BBB) is a selective semi-permeable structure in the central nervous system (CNS) and has many structural and functional characteristics. It regulates the transfer of molecules, ions, and cells between blood and CNS. Its components include interneurons, astrocytes, microglia, oligodendrocytes, basal lamina, pericytes, endothelial cells, extracellular matrix, and blood. The BBB plays a critical role protecting the brain parenchyma during the ischemic and hemorrhagic stroke. However, this barrier’s integrity is disrupted during ischemic stroke. Pathophysiological mechanisms in stroke induce cerebral edema associated with BBB injury. Many immune reactivations occur in patients with stroke. Especially, neutrophils play a critical role in the BBB disruption. Monocytes have proinflammatory or anti-inflammatory activity related with the type and duration of stroke. In addition, lymphocytes, microglia, astrocytes, pericytes, natural killer (NK) are the other main immune cells in this period. Previous studies reported that some strategies for stabilization of BBB yield positive functional outcome in stroke. Inhibition of neutrophil infiltration with reparixin and junctional adhesion molecule A antagonist peptide (JAM-Ap) is effective treatment approach to reduce infarct volume and neurological deficits. Regulation of neutrophil polarization (all-trans retinoic acid, rosiglitazone, etc.) is another neutrophil-related treatment option. Fingolimod, a S1P receptor agonist, modulates immune homeostasis and reduces hemorrhagic transformation. Microglial regulation, cytokine, and astrocyte inhibition are another BBB-related treatment approach. In conclusion, the severity of BBB’ injury is associated with poor functional outcome in ischemic and hemorrhagic stroke. In particular, studies on functional and structural stabilization of BBB may provide significant positive contributions in stroke treatment.