New progress in the approaches for blood–brain barrier protection in acute ischemic stroke

Ischemic stroke is a disease with high morbidity and mortality worldwide, which often places an additional strain on families and society due to the poor prognosis. Blood brain-barrier (BBB) damage is the critical pathological process, which contributes to hemorrhagic transformation (HT) and poor prognosis in cerebral ischemia. Thus, there is a pressing need to seek an approach to ameliorate BBB damage and reduce the HT that can be induced by fibrinolytic therapy involving recombinant tissue plasminogen activator (rtPA) in clinical practice. This review provides an overview of the recent scientific reports to improve our understanding of new approaches to ameliorating BBB damage in ischemic stroke, including physical approaches, chemical agents, traditional Chinese medicine and its extracts, neural stem cell therapy and microRNA intervention. Inhibiting matrix metalloproteinases (MMP) is possibly the main functional mechanism of these BBB protectants, along with anti-oxidative and anti-inflammatory effects. Other significant mechanisms for BBB protection have been studied recently, such as anti-apoptosis, extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/ Akt pathways and so on. An in-depth understanding of the related mechanisms contributes to finding potential approaches for BBB protection, and a deeper understanding of the emerging BBB protectants offers opportunities to seek a promising adjuvant therapy to prevent HT in the post-stroke brain.