Oligodendrocyte integrin-β1 regulates blood-brain barrier and remyelination in hemorrhagic brain

Intracerebral hemorrhage (ICH) causes high rates of mortality and long-term disability, but there are no effective treatments currently. Two key pathologies of ICH are blood-brain barrier (BBB) damage and white matter injury. Previous studies show that oligodendrocytes (OLs) regulate BBB integrity and (re)myelination via the extracellular matrix (ECM). The receptors that mediate these functions, however, remain incompletely understood. Here, we investigated the function of OL-derived integrin-β1 under both homeostatic and ICH conditions using conditional knockout mice. The mutant mice were grossly normal with intact BBB and OL maturation/myelination under homeostatic conditions. After ICH, however, these mutants exhibited exacerbated brain injury, including larger hematoma volume, elevated brain edema, aggravated axonal injury, enhanced BBB damage, compromised OL differentiation/maturation, impaired remyelination, and worsened neurological dysfunction. Subsequent studies revealed that the enhanced BBB injury was mediated by both paracellular and transcellular mechanisms and associated with pericyte defects. These findings demonstrate that OL-derived integrin-β1 is dispensable under homeostatic conditions but strictly required for BBB repair and remyelination following hemorrhagic stroke.