Glibenclamide Attenuates Brain Edema After Intracerebral Hemorrhage Through Preservation of Blood-Brain Barrier Integrity and Glymphatic Function.

Brain edema is a major contributor to secondary injury following intracerebral hemorrhage (ICH). Neurochemical disturbances, including disruption of blood-brain barrier (BBB) tight junctions and altered aquaporin-4 (AQP4) polarization, are central to post-hemorrhagic fluid imbalance. However, their association with glymphatic dysfunction and tissue-level alterations remains incompletely understood. A rat model of ICH was established and treated with glibenclamide. BBB integrity, glymphatic function, and AQP4 polarization were systematically evaluated using molecular, histological, and tracer-based approaches. Brain edema and perihematomal tissue mechanical properties were assessed. ICH was associated with marked disruption of BBB integrity, characterized by reduced tight junction protein expression and increased permeability, along with impaired AQP4 polarization and diminished glymphatic influx and clearance. These coordinated neurochemical alterations were accompanied by secondary changes in cerebrospinal fluid composition, brain water accumulation, and tissue mechanical properties. Glibenclamide treatment was associated with preservation of tight junction protein expression, restoration of AQP4 polarization, and improved glymphatic transport dynamics, accompanied by attenuation of edema formation and partial normalization of perihematomal tissue mechanics. Functional performance was correspondingly improved in treated animals. These findings indicate that experimental ICH was accompanied by coordinated changes in BBB integrity, AQP4 polarization, and fluid transport dynamics. Glibenclamide treatment was associated with parallel improvements across molecular, physiological, and functional domains. Collectively, the data highlight a coordinated pattern of neurovascular and fluid homeostasis alterations that may be involved in edema progression after hemorrhagic injury.