Focusing on claudin-5: A promising candidate in the regulation of BBB to treat ischemic stroke

• Published in: Progress in neurobiology Vol. 161; pp. 79 - 96
• Main Authors: Lv, Jianjun, Hu, Wei, Yang, Zhi, Li, Tian, Jiang, Shuai, Ma, Zhiqiang, Chen, Fulin, Yang, Yang
• Format: Journal Article
• Language: English
• Published: England 01.02.2018
• Subjects: Therapy; Claudin-5; Tight junction; Blood-brain barrier; Ischemia; Caveolin
• ISSN: 0301-0082; 1873-5118; 1873-5118
• DOI: 10.1016/j.pneurobio.2017.12.001

Claudin-5 is a tight junction (TJ) protein in the blood-brain barrier (BBB) that has recently attracted increased attention. Numerous studies have demonstrated that claudin-5 regulates the integrity and permeability of the BBB. Increased claudin-5 expression plays a neuroprotective role in neurological diseases, particularly in cerebral ischemic stroke. Moreover, claudin-5 might be a potential marker for early hemorrhagic transformation detection in ischemic stroke. In light of the distinctive effects of claudin-5 on the nervous system, we present the elaborate network of roles that claudin-5 plays in ischemic stroke. In this review, we first introduce basic knowledge regarding the BBB and the claudin family, the characterization and regulation of claudin-5, and association between claudin-5 and other TJ proteins. Subsequently, we describe BBB dysfunction and neuron-specific drivers of pathogenesis of ischemic stroke, including inflammatory disequilibrium and oxidative stress. Furthermore, we summarize promising ischemic stroke treatments that target the BBB via claudin-5, including modified rt-PA therapy, pharmacotherapy, hormone treatment, receptor-targeted therapy, gene therapy, and physical therapy. This review highlights recent advances and provides a comprehensive summary of claudin-5 in the regulation of the BBB and may be helpful for drug design and clinical therapy for treatment of ischemic stroke.