Vepoloxamer Promotes Functional Recovery in Rats After Traumatic Brain Injury with a broad therapeutic Window

Introduction: Vepoloxamer is an amphiphilic polyethylene- polypropylene-polyethylene tri-block copolymer that seals membranes and restores plasma membrane integrity in damaged cells..This dose-response and therapeutic window study of Vepoloxamer treatment of traumatic brain injury(TBI) in rats was conducted to investigate its potential therapeutic benefits

Methods: To find the most effective dose of Vepoloxamer, adult male Wistar rats injured with controlled cortical impact (CCI) were treated with 0 (vehicle), 100, 300, or 600 mg/kg of Vepoloxamer intravenously (IV) at 2h after TBI (n=10 per group). After that, we performed a therapeutic window measurement in which the rats were treated with the most effective dose at 2 h, 4 h, 1 day or 3 days after TBI (n=10 per group).. A battery of cognitive and neurological functional tests including Neurological severity scores (NSS),Foot-fault and Morris Water Maze (MWM) tests were performed after TBI. Animals were killed 35 days after TBI and brains were harvested for histopathological analysis.

Results: Dose-response experiments showed that Vepoloxamer at all three tested doses (100, 300, 600 mg/kg) administered 2 h post injury significantly improved cognitive functional recovery,whereas Vepoloxamer at doses of 300 and 600 mg/kg, but not 100mg/kg,significantly reduced the lesion volume compared to saline treatment.However,Vepoloxamer at 300 mg/kg had the most effective therapeutic effect on improvements of neurological and cognitive functions. In addition, our data demonstrated that the most effective dose (300 mg/kg) of Vepoloxamer initiated 2 h, 4 h, 1 day or 3 days post injury significantly improved neurological function, with the most robust effect seen at 2 h post injury administration

Conclusion : The present study demonstrated that Vepoloxamer improves functional recovery in a dose-and time-dependent manner and the treatment is still effective even when initiated 3 days post TBI.However,the maximum benefit is seen with the optimum dose administered 2 h post TBI.This enhanced therapeutic window increases the clinical relevance of Vepoloxamer as a potential treatment of TBI.

Keywords: Vepoloxamer, functional outcome, rat, traumatic brain injury