Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran; Institute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, Iran.
J Stroke Cerebrovasc Dis. 2021 Apr;30(4):105630. doi: 10.1016/j.jstrokecerebrovasdis.2021.105630. Epub 2021 Jan 23.
The therapeutic effects of dimethyl fumarate (DMF) in patients with multiple sclerosis and animal models of neurologic disease were reported. The density and the distribution pattern of motor neurons are important in transmitting the signal and controlling the movement-related functions. The present study evaluated the effects of DMF treatment on the neurological functions, infarct volume, and spatial distribution of the neurons in the primary motor cortex after cerebral ischemia.
Thirty-three Sprague-Dawley rats were randomly divided into three groups: The sham group underwent surgery without middle cerebral artery occlusion (MCAO) and drug. The vehicle and treatment groups after MCAO received a vehicle or DMF for three consecutive days. Post-stroke neurological and motor functions were assessed. At the end of the third day, the brains were removed, and the cerebral infarct volume was evaluated. We used cresyl violet staining to analyze the density and the spatial arrangement of motor cortical neurons using Voronoi tessellation.
Treatment of the brain ischemia for three days with DMF could not significantly reduce the neurological and motor function deficits and infarct volume. However, it reduced the neuronal area and death and preserved their spatial distribution in the normal regular pattern.
Cerebral ischemia decreased the neuronal density of the primary motor cortex and changed their distributions to a random pattern. DMF treatment during sub-acute ischemic stroke did not significantly improve the neurological deficit scores. However, it could prevent neuronal swelling and death and preserved the spatial distribution of the cortical neurons in their normal pattern.
富马酸二甲酯（DMF）在多发性硬化症患者和神经疾病动物模型中的治疗效果已有报道。运动神经元的密度和分布模式对于传递信号和控制与运动相关的功能非常重要。本研究评估了 DMF 治疗对脑缺血后初级运动皮层神经元的神经功能、梗死体积和空间分布的影响。
33 只 Sprague-Dawley 大鼠随机分为三组：假手术组不进行大脑中动脉闭塞（MCAO）和药物治疗；载体组和治疗组在 MCAO 后接受载体或 DMF 连续治疗 3 天。卒中后神经和运动功能进行评估。在第 3 天结束时，取出大脑，评估脑梗死体积。我们使用甲苯胺蓝染色，通过 Voronoi 图分析运动皮质神经元的密度和空间排列。
DMF 治疗脑缺血 3 天不能显著减轻神经和运动功能缺陷及梗死体积。然而，它减少了神经元的面积和死亡，并保持了它们在正常规则模式下的空间分布。
脑缺血降低了初级运动皮层的神经元密度，并改变了它们的分布模式为随机模式。亚急性缺血性卒中期间的 DMF 治疗不能显著改善神经功能缺损评分。然而，它可以防止神经元肿胀和死亡，并保持皮质神经元在正常模式下的空间分布。
