Evaluation of the Effect of Nebivolol on Hippocampus in Experimental Traumatic Brain Injury

Abstract Objective: Traumatic brain injury (TBI) is a major cause of mortality and long-term disability worldwide. Secondary injury mechanisms such as oxidative stress, neuroinflammation, and astroglial activation contribute significantly to neuronal degeneration, particularly in the hippocampus. Nebivolol, a third-generation β1-adrenergic blocker with nitric oxide–mediated vasodilatory and antioxidant properties, has been proposed as a potential neuroprotective agent. This study aimed to investigate the histopathological and immunohistochemical effects of nebivolol on hippocampal damage after experimental TBI in rats, with a specific focus on S100 protein expression as a marker of astroglial activation. Materials and Methods: Twenty-four male Sprague–Dawley rats were randomly divided into three groups (n = 8 each): Control, TBI, and TBI + Nebivolol. TBI was induced using the weight-drop method (50 g/1 m). Nebivolol was administered orally at a dose of 10 mg/kg/day for 14 days. Hippocampal tissues were collected on day 14 and examined histologically with hematoxylin–eosin (H&E) and immunohistochemically for S100 expression. Statistical analyses were performed using one-way ANOVA or Kruskal–Wallis tests, with p < 0.05 considered significant. Results: In the TBI group, marked neuronal degeneration, nuclear pyknosis, vascular dilatation, and synaptic disorganization were observed in the hippocampus. Strong S100 expression was detected in pyramidal neurons, glial cells, and vascular endothelium, indicating astroglial activation. In contrast, the TBI + Nebivolol group exhibited preserved neuronal morphology, reduced vascular dilatation, and improved axonal organization. Immunohistochemically, S100 expression was significantly decreased in pyramidal neurons and glial cells compared to the TBI group, suggesting attenuation of astrocytic activation. Conclusion: Nebivolol treatment ameliorated hippocampal injury in rats with experimental TBI by reducing oxidative stress–related histopathological changes and suppressing S100 expression. These findings support the potential role of nebivolol as a neuroprotective agent in TBI by limiting astroglial activation and secondary neuronal damage. Further studies with larger cohorts, additional molecular analyses, and behavioral assessments are needed to confirm its therapeutic potential.