The effect of S-ketamine administration on improving memory and learning following cerebral ischemia and reperfusion in male Wistar rats

Introduction: This study investigated the effect of S-ketamine administration as a neuroprotective treatment for necrotic cell death and memory and learning impairments following a cerebral ischemia model in male rats. Methods: In this experimental study, 28 male Wistar rats with weighing between 250-300 g, were randomly divided into four groups: Sham, Ischemia-Saline, Ischemia-S-ketamine (low dose), and Ischemia-S-ketamine (high dose).In the ischemia groups receiving low and high doses of S-ketamine, the drug was administered immediately right after the onset of ischemia at doses of 0.1 mg/kg and 0.25 mg/kg body weight, respectively. Memory and learning were evaluated in the different groups through the passive avoidance learning test. Four days after induction of ischemia, necrotic cell death was measured using Cresyl violet staining. Data were analyzed using SPSS software. Results: The results showed that in the ischemia-saline group, significantly increased in the number of necrotic cells compared to the sham group (p<0.05). Treatment with S-ketamine substantially decreased necrotic cell death in the CA1 region of the hippocampus. The reduction in ischemia-induced cell death was more significant in the high-dose S-ketamine treatment group compared to the low-dose S-ketamine treatment group (p<0.05). Moreover, S-ketamine treatment improved memory and learning deficits caused by ischemia in a dose-dependent manner. Conclusion: Treatment with S-ketamine has been able to affect the consequences of cerebral ischemia, and therefore the introduction of S-ketamine therapy is proposed as a new therapeutic method in the treatment of cerebral ischemia.