Neuroprotective Effect of Paroxetine on Memory Deficit Induced by Cerebral Ischemia after Transient Bilateral Occlusion of Common Carotid Arteries in Rat.

Abstract

Memory deficit is the most visible symptom of cerebral ischemia. The hippocampus is sensitive against cerebral ischemia. Oxidative stress and inflammation are involved in the pathological process after cerebral ischemic injury. Paroxetine has anti-oxidative and anti-inflammatory effects. In this study, the effect of paroxetine on memory deficit after cerebral ischemia was investigated. Cerebral ischemia/reperfusion (I/R) injury model was established using the bilateral occlusion of common carotid artery method. Paroxetine (10 mg/kg) was intraperitoneally injected into rats, 24 h before surgery or once a day for 7 days after surgery. Learning and memory were evaluated using the Morris water maze task, then the brain tissue was fixed and hippocampal CA1 pyramidal cells damage was analyzed using the Nissl staining method. In the ischemia group the escape latency time (ELT) and the swimming path length (SPL) were significantly increased and the time spent in target quadrant (TSTQ) was significantly decreased compared with the control group. The ELT and the SPL were significantly shortened and the TSTQ was significantly increased compared with the ischemia group after Pre- or post-ischemic administration of paroxetine. The percentage of viable pyramidal cells in the ischemia group was significantly decreased compared with the control group. The percentage of viable cells was significantly increased following pre-or post-ischemic administration of paroxetine compared with the ischemia group. Memory deficit due to I/R was improved and the percentage of viable cells in CA1 region was increased after administration of paroxetine. Therefore, paroxetine may have a neuroprotective effect against cerebral ischemia.