Comparing Effects of Nicorandil and Dimethyl Fumarate in a Rat Model of Cerebral Ischemia

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 385

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شناسه ملی سند علمی:

NIMED03_122

تاریخ نمایه سازی: 7 آبان 1398

چکیده مقاله:

Blood-brain barrier (BBB) disruption and production of oxygen free radicals are major pathogenic mechanisms in ischemic stroke. It is suggested that dimethyl fumarate (DMF) may improve BBB integrity and neurological function in stroke and its effects might be mediated via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nicorandil protects the brain against ischemic injury through its antiinflammation and anti-apoptotic properties. Current research attempted to elucidate the effects of DMF and nicorandil on BBB integrity and neurological function recovery of rats after middle cerebral artery occlusion (MCAO) and clarify the NF-κB and Nrf2-dependentmechanisms modulated by these drugs. Materials and Methods: Rats were subjected to 1h MCAO, followed by 3 days of reperfusion. 48 Sprague-Dawley male rats were allocated into four groups (n=12): the sham group was just subjected to surgery stress; vehicle, DMF, andnicorandil groups, after MCAO received vehicle, 30 mg/kg DMF, and 5 mg/kg nicorandil, respectively for 3 days after MCAO. Modified neurological severity scores was evaluated every day. Triphenyltetrazolium chloride was just utilized to approve MCAO and BBBdisruption was evaluated by extravasation of Evans blue. RT-PCR was done to analyze the expression levels of nuclear factor (NF)-κB and Nrf2. Results: Both drugs improved ischemia-induced BBB disruption and promote the expression of Nrf2, however, just DMF significantly improved neurobehavioral function and the expression of NF-κB was only promoted by nicorandil. Conclusion: DMF improved neurobehavioral outcome and BBB disruption in ischemic stroke, probably through upregulation of Nrf2 but nicorandil did not have prominent effect on stroke

نویسندگان

Maryam Owjfard

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

Mohammad Reza Bigdeli

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

Anahid Safari

Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Mohammad Reza Namavar

Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran