Protective Effect of Dimethyl Fumarate on Memory Impairment After Cerebral Ischemia-Reperfusion Injury in Rats

Abstract

Background: Cerebral ischemia is an important cause of morbidity and mortality worldwide. Dimethyl fumarate (DMF) is indicated for the treatment of patients with relapsing forms of Multiple Sclerosis and psoriasis. Objectives: In this study, the effect of DMF on memory and learning impairments and nitrosative stress after cerebral ischemia in rats, was evaluated. Methods: Cerebral ischemia was induced via common carotid artery occlusion (CCAO). Rats were randomly divided into three groups (N = 5). Group I included Sham-operated animals who underwent surgery without arterial occlusions, group II (control ischemic) underwent surgery to induce transient global cerebral ischemia for 20 min and received 0.2 - 0.25 mL of distilled water, twice a day by oral gavage, group III included rats which underwent cerebral ischemia and then received DMF (15 mg/kg, twice daily, for 1 week) by oral gavage. Morris water maze test was used to assess spatial memory. Nitric oxide (NO) level in the hippocampus was measured using Griess test. Results: Treatment of rats with DMF (15 mg/kg, orally, twice daily for 7 days) resulted in a significant decrease in escape latency during training trials. Besides, the time spent in the target quadrant and the number of crossings over the platform area were significantly increased in the DMF-treated rats which were accompanied by a decrease in the proximity to the platform in the probe trial. Furthermore, the results of the Griess assay indicated a significant reduction in the NO levels in the hippocampus of DMF-treated rats. Conclusions: Overall, our findings indicate that DMF improves memory impairment induced by cerebral ischemia/reperfusion injury in rats through the suppression of nitrosative stress in the hippocampus.