Tehran University of Medical Sciences Current Journal of Neurology 2717-011X 18 3 2019 07 06 108 113 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 2018 12 17 2019 06 16 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. https://ijnl.tums.ac.ir/index.php/ijnl/article/view/1705