Glibenclamide attenuates brain edema after intracerebral hemorrhage by improving blood–brain barrier integrity glymphatic transport and tissue poroelastic properties

Background: Brain edema is a major determinant of secondary injury and poor neurological outcome after intracerebral hemorrhage (ICH). Disruption of the blood-brain barrier (BBB), impaired cerebrospinal fluid (CSF) homeostasis, and astrocytic dysfunction are recognized contributors to edema formation; however, how these processes interact with glymphatic transport and tissue-level biophysical properties after ICH remains incompletely characterized. Methods: A rat model of ICH was established and treated with glibenclamide. BBB integrity was evaluated by Evans blue extravasation, tight junction protein expression, and immunofluorescence. CSF protein concentration was quantified, and glymphatic influx and clearance were assessed using fluorescent tracer-based approaches together with analysis of aquaporin-4 (AQP4) polarization. Brain edema was measured by wet-dry weight analysis and magnetic resonance imaging. In addition, poroelastic mechanical testing was performed to characterize edema-associated alterations in brain tissue properties. Neurological function was assessed using behavioral tests. Results: ICH resulted in BBB disruption, elevated CSF protein levels, impaired AQP4 polarization, reduced glymphatic influx and clearance, increased brain edema, and altered poroelastic parameters of perihematomal tissue. Glibenclamide treatment was associated with partial restoration of BBB integrity, reduction of CSF protein accumulation, improvement of glymphatic transport, attenuation of brain edema, and normalization of tissue poroelastic properties. These changes were accompanied by improved long-term neurological performance. Conclusions: These findings provide an integrated experimental characterization linking vascular permeability, glymphatic transport, and tissue poroelastic dynamics in brain edema following intracerebral hemorrhage. Glibenclamide treatment was associated with coordinated improvement across these pathways, supporting a pathophysiological nexus between fluid homeostasis and tissue mechanics after hemorrhagic injury.