Abbreviated levetiracetam treatment effects on behavioural and histological outcomes after experimental TBI

Abstract

Objective: Long-term prophylactic treatment with levetiracetam (LEV) has multiple neuroprotective effects in a traumatic brain injury (TBI) rat model. Although a rational time-frame of seizure prophylactic treatment with LEV for after TBI is not well established, clinical prophylaxis with LEV often includes treatment duration similar to clinical treatment guidelines with Phenytoin. Thus, this study investigated the effects of abbreviated LEV treatment on behavioural function and histological evidence of neuroprotection.Research design: Pre-clinical trial of abbreviated LEV dosing in an experimental model of TBIMethods: After either controlled cortical impact (CCI) injury or sham surgery, rats received three 50 mg kg−1 doses over 24 hours or vehicle. After injury/sham surgery, beam performance, spatial learning, contusion volume size and hippocampal neuron survival were assessed.Results: Abbreviated LEV did not improve motor or cognitive performance after TBI. Further, abbreviated LEV did not improve hippocampal neuron sparing or contusion volumes compared with vehicle controls.Conclusions: Together with previous work assessing daily LEV treatment, these results suggest that longer-term therapy may be required to confer beneficial effects within these domains. These findings may guide (1) future experimental studies assessing minimal effective dosing for neuroprotection and anti-epileptogenesis and (2) treatment guideline updates for seizure prophylaxis post-TBI.