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Paroxetine Attenuates Cerebral Ischemia/Reperfusion Injury in Rat Via Its Anti-Inflammatory and Antioxidant Effects

Abstract

Cerebral ischemia is often associated with sensory-motor impairment and memory deficit. Previous studies have demonstrated that paroxetine, the antidepressant drug, exhibits anti-inflammatory and antioxidant effects. In this study, we investigated the protective effects of paroxetine on neuronal damage and activation of microglial cells induced by cerebral ischemia/reperfusion in the rat. Cerebral ischemia/reperfusion injury was induced by transient bilateral common carotid artery occlusion. The Wistar rats were assigned to sham, ischemia, and paroxetine-treated groups. Paroxetine (10 mg/kg) was administered intraperitoneally once daily for 7 days subsequent to surgery. In order to evaluate spatial memory in rats, Morris water maze test (MWM) was conducted. The viability of pyramidal neurons in the hippocampus was assessed by Nissl staining method. Microglial activation and production of pro-inflammatory cytokines (IL-1β, TNF-α) were examined using Iba1-immunostaining and ELISA methods, respectively. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) in homogenates of hippocampal tissue. In MWM test, paroxetine significantly enhanced learning performance in rats subjected to cerebral ischemia/reperfusion. Our findings indicated that paroxetine significantly suppressed ischemia-induced microglial activation and decreased the IL-1β and TNF-α level in the hippocampus. In addition, paroxetine inhibited lipid peroxidation and decreased MDA levels in homogenates of hippocampal tissue. These results establish that paroxetine exert a protective effect against cerebral ischemia/reperfusion-induced damage to hippocampal neurons and memory impairment in rats through anti-inflammatory and antioxidant effects.

Yazdan Naderi*

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