Evaluating the Neuroprotective Effects of Levetiracetam on Experimental Sciatic Nerve Injury

Background/Objectives: Despite surgical interventions, patients experience incomplete nerve function recovery following peripheral nerve (PN) injuries. Levetiracetam (LEV), a third-generation antiepileptic agent and neuromodulator, has shown neuroprotective effects in conditions such as traumatic brain injury and diabetic neuropathy. However, its efficacy in PN injuries remains unexplored. Methods: We conducted an experimental study using 48 rats divided into six groups. After inducing sciatic nerve compression, LEV was administered intraperitoneally at 50 mg/kg/day for 7 days in the acute group and for 28 days in the chronic group. The sciatic functional index (SFI) was assessed on the 7th day in the acute group and on the 7th, 14th, 21st, and 28th days in the chronic group. Histological and tissue assessments were performed post-sacrifice (7th day for acute; 28th day for chronic). Results: Significant differences were observed among the groups in all parameters except capillary structure and inflammatory cell density. LEV-treated groups demonstrated higher GAP-43 and S-100 reactivity, improved SFI scores, and greater neuronal regeneration compared to non-drug groups (p < 0.05). LEV significantly enhances neuronal regeneration, protein expression (GAP-43 and S-100), and SFI outcomes, particularly in the chronic phase. Conclusions: This experimental animal study is the first to demonstrate LEV's therapeutic potential in PN injury, providing a basis for further exploration.