Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Autor: Maryam Owjfard, Mohammad Reza Bigdeli, Anahid Safari, Mohammad Reza Namavar
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Brazilian Journal of Pharmaceutical Sciences, Vol 58 (2022)
Druh dokumentu: article
ISSN: 2175-9790
DOI: 10.1590/s2175-97902022e19677
Popis: Abstract Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression.
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