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) have displayed great potential in ameliorating brain damage following intracerebral hemorrhage (ICH) via proliferation, differentiation, and immunomodulation. However, it remains unclear whether NSCs can improve microvascular function, e.g., blood-brain barrier (BBB) integrity, after ICH. In this study, we investigate the potential therapeutic benefit of NSCs on BBB integrity as well as 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 ICH induction. The following multiparametric measurements were compared: brain edema, hematoma volume, behavior, 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. These findings provide novel insight for future therapies aiming to prevent BBB dysfunction and improve functional recovery in ICH patients.