Therapeutic evaluation of tumor necrosis factor-alpha antagonist etanercept against traumatic brain injury in rats: Ultrastructural, pathological, and biochemical analyses

Purpose: The aim of the present study was to investigate the effect of etanercept (ETA) on histopathological and biochemical changes after traumatic brain injury (TBI) in rats. Materials and Methods: Thirty-six male Wistar albino rats were distributed into three groups (n = 12 each). Control group rats were not subjected to trauma. Trauma group rats were subjected to TBI only. ETA group rats were subjected to TBI plus ETA (5 mg/kg intraperitoneal [i.p.]). The groups were further subdivided into those sacrificed in the hyperacute stage (1 h after TBI) (control-1, trauma-1, and ETA-1 groups) and the acute stage (6 h after TBI) (control-6, trauma-6, and ETA-6 groups). Tissue levels of tumour necrosis factor-alpha, interleukin-1 beta, malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase were analyzed. Histopathological and ultrastructural evaluations were also performed. Results: i.p. administration of ETA at 1 and 6 h significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to trauma group. Histopathological and ultrastructural abnormalities were significantly reduced in ETA-treated rats compared to closed head injury trauma groups. Conclusions: ETA significantly improves neural function and prevents post-TBI histopathological damage in rats.

Key-words:

Etanercept - rat - traumatic brain injury - tumor necrosis factor-α antagonist