Potential dose dependent neuro protective effect of ketamine on the brain in the head trauma model in rats

Objective: In our study, we aimed to investigate the neuroprotective and anti-inflammatory effects of ketamine, which has immunomodulatory effects, in an experimental head injury model in rats. Methods: The rats were divided into six groups (n: 6) as control, trauma and ketamine-treated trauma (Trauma+10, Trauma+20, Trauma+40 and Trauma+60mg/kg ketamine). Ketamine was administered intraperitoneally every day until the seventh day after the trauma. Neurological examination was performed on the 24th, 48th hours and seventh day after the trauma. Serum IL-1β, IL-10, TNF-α levels were measured at the 24th hour and seventh day. On the seventh day the serum and brain levels of lipid peroxidase (MDA), glutathione peroxidase, catalase, caspase-3 and serum levels of AST, ALT, ALP, BUN, creatinine and LDH were studied. Hematoxylin-Eosin staining was performed for histopathological evaluation of brain tissue and TUNEL staining for apoptosis. Statistical analysis was performed by one-way and two-way analysis of variance (ANOVA). Results: Neurological examination scores were impaired in the ketamine 60mg/kg group (p<0.05) and a decrease in IL-1β levels was observed in the 40mg/kg ketamine group (p<0.05) on the seventh day. Brain levels of glutathione peroxidase were decreased at 60mg/kg ketamine dose compared to other doses (p<0.05). At the dose of ketamine 60mg/kg, an increase in brain values of MDA were observed on the seventh day (p<0.001). Necrosis was observed in histopathological examinations. Conclusion: 60mg/kg ketamine dose had a negative effect on neurologic examination scores, IL-1β, brain glutathione peroxidase and MDA levels. 40mg/kg ketamine dose had a positive effect on IL-1β. No beneficial or harmful effects of ketamine were observed at other doses. As the most important finding, ketamine, at doses other than 60 mg/kg, played a protective role by preventing the worsening of post-traumatic injuries.