Minocycline Improves Memory in a Passive Avoidance Task Following Cerebral Ischemia-Reperfusion By Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in Rats

Abstract

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia which ultimately results in memory dysfunction. Hence, application of antioxidant agents could be beneficial in the management of memory deficit after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemia-reperfusion injury in rats. Single or multiple (once daily for 7 days) doses of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, hippocampal long-term potentiation, and the activity of antioxidant enzymes were assessed. Results: The results of passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reduced the duration of staying in dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats which were treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus. Conclusion: It was ultimately determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats through the improvement of hippocampal synaptic plasticity and restoration of antioxidant enzymes activity.