Neuroprotective effects of ceftriaxone after severe traumatic brain injury in male rats: a behavioral, biochemical, and histological study.

Background: Only a limited number of animal studies have demonstrated the neuroprotective effects of single dose of ceftriaxone (CTX) in traumatic brain injury (TBI). Consequently, the present study seeks to fill these research gaps by examining the impact of CTX on neurological and motor performance, brain edema, and blood-brain barrier (BBB) permeability in a rat model of severe diffuse TBI. Methods: Ninety-eight male Albino Wistar rats were subjected to TBI using the Marmarou method. The rats were divided into seven groups, each consisting of 14 animals: Intact, Sham, TBI, Vehicle (TBI + saline placebo injection), and three groups receiving single intraperitoneal (IP) injections of CTX at doses of 100, 200, and 400 mg/kg. Post-trauma assessments included measurements of the brain water content (BWC), BBB permeability, Veterinary Coma Scale (VCS), beam-walk (BW), beam-balance (BB), IL-10, IL-1β, TNF-α, and INF-γ concentrations, liver and kidney function tests, and histopathological analysis. Results: Administration of CTX at doses of 100 and 200 mg/kg resulted in significantly reduced BWC, enhanced BBB integrity, improved VCS scores, better performance on BW and BB tests, reduced IL-1β, TNF-α, and INF-γ, and increased IL-10, along with favorable histopathological outcomes and no signs of systemic toxicity. However, increasing the dose to 400 mg/kg did not yield further improvement. Conclusion: Our results demonstrate that CTX administration at doses of 100 and 200 mg/kg significantly improved neurological and motor function, reduced cerebral edema, enhanced blood-brain barrier integrity, and favorably modulated the post-traumatic inflammatory response. In contrast, the 400 mg/kg dose conferred no additional benefit.