CNS lesions usually result in permanent loss of function and are an important problem in the medical field. In order to investigate neuroprotection/degeneration mechanisms and the synaptic plasticity of motoneurons, in addition to the potential for a variety of treatments, different experimental models of axonal injury have been proposed. Recent studies have tested the immunomodulatory drug dimethyl fumarate (DMF) for the treatment of neurodegenerative diseases and have shown promising outcomes. Therefore, in this work, we investigated the effects of DMF with regard to neuroprotection and its influence on the glial response in C57BL/6J animals subjected to crushing of the motor roots in the lumbar intumescence of the spinal cord. The animals were divided into a vehicle-treated injury group (0.08 % methylcellulose solution control group, n = 7) and injured groups treated with DMF at different doses (15, 30, 45, 90 and 180 mg/kg; n = 6–7 per dose). The 90 mg/kg dose showed the best neuroprotective results, so it was used for treatment over a period of eight weeks. Neuronal survival was assessed through Nissl staining, and functional recovery was evaluated with the CatWalk system (walking track test) and the von Frey test (mechanoreception). Immunohistochemistry was used to assess synaptic coverage and astroglial and microglial reactivity using the primary antibodies anti-synaptophysin (pre-synaptic terminal pan marker), GAD65 (GABAergic pre-synaptic terminations - inhibitory), and VGLUT1 (glutamatergic pre-synaptic terminations - excitatory). Glial reactions were evaluated with anti-IBA1 (microglia) and GFAP (astrocytes). Gene transcript levels of IL-3, IL-4, TNF-α, IL-6, TGF-β, iNOS-M1, and arginase-M2 were quantified by RT-qPCR. The results indicated that treatment with DMF, at a dose of 90 mg/kg, promoted neuroprotection and immunomodulation towards an anti-inflammatory response. It also resulted in greater preservation of inhibitory synapses and reduced astroglial reactivity, providing a more favorable environment for sensorimotor recovery.

中枢神经系统病变通常会导致永久性功能丧失，是医学领域的一个重要问题。为了研究运动神经元的神经保护/退化机制和突触可塑性，除了各种治疗的潜力外，还提出了不同的轴突损伤实验模型。最近的研究测试了免疫调节药物富马酸二甲酯 (DMF) 用于治疗神经退行性疾病，并显示出有希望的结果。因此，在这项工作中，我们研究了 DMF 对神经保护的影响及其对 C57BL/6J 动物的神经胶质反应的影响，这些动物在脊髓的腰部肿胀中受到运动根的挤压。将动物分为媒介物处理的损伤组（0.08%甲基纤维素溶液对照组，n = 7）和用不同剂量的 DMF（15、30、45、90 和 180 mg/kg；n = 6-7 每剂）治疗的受伤组。90 mg/kg 剂量显示出最好的神经保护效果，因此它用于治疗超过八周。通过 Nissl 染色评估神经元存活率，并使用 CatWalk 系统（步行轨迹测试）和 von Frey 测试（机械感受）评估功能恢复。免疫组织化学用于评估突触覆盖率和星形胶质细胞和小胶质细胞反应性，使用初级抗体抗突触素（突触前末端泛标记）、GAD65（GABA 能突触前终止 - 抑制性）和 VGLUT1（谷氨酸能突触前终止 - 兴奋性） . 用抗 IBA1（小胶质细胞）和 GFAP（星形胶质细胞）评估神经胶质反应。IL-3、IL-4、TNF-α、IL-6、TGF-β、iNOS-M1 和精氨酸酶-M2 通过 RT-qPCR 进行量化。结果表明，用 90 mg/kg 剂量的 DMF 处理可促进神经保护和免疫调节，从而产生抗炎反应。它还导致抑制性突触的更好保存和星形胶质细胞反应性降低，为感觉运动恢复提供了更有利的环境。