Poloxamer 188 Enhances Tight Junction Reassembly and Reduces Permeability in Brain Endothelium Disruption

Abstract Disruption of the blood–brain barrier (BBB) after stroke or traumatic brain injury (TBI) exacerbates cerebral edema, in?ammation, and neuronal damage. Tight junctions (TJs) between endothelial cells are critical for barrier function, yet few therapies directly target TJ reassembly. Poloxamer 188 (P188), an FDA-approved amphiphilic triblock copolymer, has demonstrated membrane-stabilizing and vascular-protective properties in diverse injury models. We hypothesized that P188 promotes BBB recovery by sealing compromised membranes and enhancing TJ reassembly. Using a 96-Transwell mouse brain endothelial cell model, barrier disruption was induced with 0.01% Triton X-100, and permeability assessed by 70 kDa fluorescent dextran flux and zonula occludens-1 (ZO-1) immunostaining. Triton treatment increased dextran flux and disrupted ZO-1 localization, whereas P188, applied before or after injury, significantly reduced permeability and restored ZO-1 intensity to control levels. In vivo, ?uorescently conjugated P188 (3 mg/kg) administered intravenously in mice accumulated in the brain within 6 h, suggesting the ability to reach sites of BBB injury. These findings support a dual role for P188 in BBB repair—mechanical stabilization of damaged membranes and structural restoration of TJs. Combined with its established safety, P188 emerges as a promising candidate for therapeutic intervention in acute neurovascular disorders, warranting further investigation in preclinical models of stroke and TBI.