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

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

Effects of nicorandil on neurobehavioral function, BBB integrity, edema and stereological parameters of the brain in the sub-acute phase of stroke in a rat model

Blood–brain barrier (BBB) disruption, inflammation, and cell death are the pathogenic mechanisms of cerebralischemia/reperfusion (I/R) injury. Nicorandil protects ischemic injury via some of these mechanisms. The aimof this study was to investigate the therapeutic effects of this drug on the brain ischemia after transient middlecerebral artery occlusion (MCAO) and clarify the NF-jB and Nrf2-dependent mechanisms modulated by thisdrug. Sixty-six rats were randomized into sham, MCAO and MCAO ? nicorandil groups with oral gavage for3 days. Cerebral I/R injury were induced by a transient MCAO for 1 h and neurobehavioral scores wereperformed for 3 days. In addition to measurement of BBB disruption and brain water content, the total andinfarct volume, density, and total number of neurons, non-neurons and dead neurons in the right cortex wereestimated by unbiased stereological methods. RT-PCR was performed to analyze the expression levels of NFjB and Nrf2. Although nicorandil treatment in the sub-acute brain ischemia did not have a prominent effect onneurobehavioral function and number of neurons, non-neurons and dead neurons probably through up-regulation of NF-jB, it, however, improved ischemia-induced BBB disruption and brain edema and showed asignificant reduction in the infarction volume probably through up-regulation of Nrf2.