Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion.

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia, ultimately resulting in memory dysfunction. Hence, the applying antioxidant agents could be beneficial in managing memory deficits after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess the 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 ischemiareperfusion injury in rats. Single or multiple (once daily for 7 days) dose(s) of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, long-term hippocampal potentiation, and the activity of antioxidant enzymes were assessed. Results: The passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reducing the duration of staying in a dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats 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 the 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 determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats by improving hippocampal synaptic plasticity and restoring antioxidant enzyme activity. Highlights: Minocycline enhances passive avoidance memory after cerebral ischemia-reperfusion.Minocycline increases enzymatic antioxidant capacity in hippocampal formation.Minocycline improves synaptic plasticity in perforant path-granule cell synapse. Plain Language Summary: Stroke is a common neurological disease with a relatively high mortality rate and disabilities worldwide. More than half of the patients who have had an episode of stroke suffer from the impairment of sensorimotor function and language problems as well as learning and memory disorders. Oxidative stress plays an important role in memory impairment following brain ischemia. Hence, the application of antioxidant agents could be beneficial in managing memory deficits after stroke. Minocycline is a tetracycline antibiotic that is used for the treatment of infectious diseases; it can also function as a potent antioxidant medication. Hence, we hypothesized that minocycline could attenuate memory impairment after brain ischemia. We examined this hypothesis in a rat model of brain ischemia. In this model, the main arteries that supply the brain with oxygenated blood were occluded to induce brain ischemia in the rats. Then, minocycline was administered to the rats, which were subjected to brain ischemia. Seven days later, memory function in the rats was evaluated. The results showed that minocycline could enhance the activity of antioxidant enzymes in the brain, which physiologically fight off oxidative stress. This property of minocycline protects brain cells against ischemic injury and thereby increases the transmission of neuronal signals from one cell to another cell in the memory centers in the brain. These effects ultimately increase the memory function of rats, which was evident in the behavioral memory test. Overall, the study results suggest that minocycline can be considered a memory enhancer drug in patients who suffer from learning and memory disorders following a stroke.