Neural stem cells protect blood-brain barrier integrity via the p38, JNK, and ERK1/2 pathways following intracerebral hemorrhage in rats

Abstract

Neural stem cells (NSCs) show high potential in ameliorating the brain damage induced by intracerebral hemorrhage (ICH) via proliferation, differentiation, and immunomodulation. However, it remains unclear whether NSCs can improve the microvascular function, e.g., blood-brain barrier (BBB) integrity after ICH. In this study, we aimed to investigate the potential therapeutic benefit of NSCs on BBB integrity and the underlying mechanism. Adult male Sprague-Dawley rats were randomly divided into sham, ICH+PBS and ICH+NSCs groups for comparisons. ICH was induced by intrastriatal injection of bacterial collagenase. An aliquot of NSCs or PBS was injected via the tail vein 2 h after the ICH induction. The following multiparametric measurements were compared: brain edema, hematoma volume, behavioral test, BBB permeability, and mitogen-activated protein kinase (MAPK) signaling pathway activity. We found that NSCs treatment attenuates BBB permeability, reduces brain edema, and promotes brain function recovery after ICH by inhibiting ERK1/2, p38 and JNK signaling pathway activation. This finding provides a novel insight for future therapies aiming to preventing BBB dysfunction and improve functional recovery in ICH patients.