Evaluation of the neuroprotective effects of methylcobalamin and citicoline treatment on nerve tissue, nerve regeneration, and scar formation in rats with experimentally induced mental nerve damage

Objective: The present study aimed to investigate the neuroprotective effects of citicoline and methylcobalamin, administered alone or in combination, on nerve regeneration and immunohistochemical markers in an experimental model of mental nerve injury. Materials and Methods: Mental nerve injury was induced in Sprague Dawley rats. Animals were divided into control, injury, and treatment groups (citicoline, methylcobalamin, and combined therapy). On days 7 and 21, animals were sacrificed, and histological (axon number and diameter), biochemical (AST, ALT, LDH, creatinine, BUN), hematological parameters, and immunohistochemical markers (Caspase-3, MMP-9, BDNF) were evaluated. Results: In the injury groups, axon number and diameter were significantly reduced, whereas all treatment groups showed improvement. Notably, combined therapy demonstrated the most pronounced regenerative effect, with a marked increase in axon number and diameter (p<0.001). On day 7, Caspase-3 and MMP-9 expression increased in the injury group, while BDNF levels were elevated. Combined therapy produced the greatest reduction in Caspase-3 and MMP-9 levels and the highest BDNF increase compared with single-agent groups. On day 21, combined therapy continued to suppress apoptotic activity and maintained the strongest support for regenerative processes, surpassing the effects of citicoline or methylcobalamin alone. Conclusion: Citicoline and methylcobalamin, particularly in combination, exert superior neuroprotective effects following mental nerve injury by enhancing axonal regeneration, strongly suppressing apoptotic pathways, and modulating BDNF. Combined therapy appears to have greater therapeutic potential than single-agent treatments for peripheral nerve injuries. Keywords: Mental nerve, Citicoline, Vitamin B12, Neuroprotection, Regeneration