Neuroprotective effect of dimethyl fumarate in stroke: The role of nuclear factor erythroid 2-related factor 2

  • Anahid Safari Stem Cells Technology Research Center, Shiraz University of Medical Sciences Shiraz, Iran
  • Hamzeh Badeli-Sarkala Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mohammad Reza Namavar Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Elias Kargar-Abarghoue Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Neda Anssari Department of Neurology, University of Manitoba, Winnipeg, Manitoba, Canada
  • Sadegh Izadi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Afshin Borhani-Haghighi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords: Stroke, Dimethyl Fumarate, Middle Cerebral Artery, Nuclear Factor E2-Related Factor 2

Abstract

Background: There is evidence that supports the neuroprotective effects of dimethyl fumarate (DMF) in stroke. Nuclear factor erythroid 2-related factor 2 (Nrf2) has both anti-oxidant and anti-inflammatory mechanisms. We investigated the neuroprotective effects of DMF via Nrf2 activation in the cortex, striatum, and diencephalon in a middle cerebral artery occlusion (MCAO) model of stroke.

Methods: 22 Sprague-Dawley male rats were randomized into 3 groups. In DMF-treated group (n = 8), rats received 15 mg/kg oral DMF twice daily by gavage from day 0 to 14 after a 60-minute MCAO. The vehicle group (n = 7) underwent MCAO and were given methocel/H2O, using the same method and schedule. In the sham group (n = 7), neck was opened, but neither middle cerebral artery (MCA) was occluded nor any drug was administered. After 14 days, the animals were sacrificed. The infarct volume were assessed by stereology method. Nrf2 expression was evaluated in the cortex, striatum, and diencephalon by immunohistochemistry method.

Results: Ratio of infarct to total brain volume was significantly lower in the DMF-treated group (5.76%) in comparison with the vehicle group (22.39%) (P < 0.0001). Nrf2 expression was higher in DMF-treated group in comparison with both the vehicle and sham groups in cortex, striatum, diencephalon, and total brain (P < 0.0001). In the DMF-treated group, significant negative correlation between Nrf2 expression and infarct volume was observed in cortex, striatum, diencephalon, and total brain.

Conclusion: DMF induces Nrf2 expression and its neuroprotective effects in different brain anatomical regions.

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Published
2019-07-06
How to Cite
1.
Safari A, Badeli-Sarkala H, Namavar MR, Kargar-Abarghoue E, Anssari N, Izadi S, Borhani-Haghighi A. Neuroprotective effect of dimethyl fumarate in stroke: The role of nuclear factor erythroid 2-related factor 2. Iran J Neurol. 18(3):108-113.
Section
Original Article(s)