Inosine Improves Functional Recovery and Cell Morphology Following Compressive Spinal Cord Injury in Mice.

IF 1.8 Q3 CLINICAL NEUROLOGY
Neurotrauma reports Pub Date : 2024-10-02 eCollection Date: 2024-01-01 DOI:10.1089/neur.2024.0081
Ricardo Cardoso, Fellipe Soares Dos Santos Cardoso, Bruna Dos Santos Ramalho, Guilherme Dos Santos Maria, Roberta Ramos Cavalcanti, Tiago Bastos Taboada, Juliana Silva de Almeida, Ana Maria Blanco Martinez, Fernanda Martins de Almeida
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Abstract

Spinal cord injury (SCI) is one of the most serious conditions of the central nervous system, causing motor and sensory deficits that lead to a significant impairment in the quality of life. Previous studies have indicated that inosine can promote regeneration after SCI. Here we investigated the effects of inosine on the behavioral and morphological recovery after a compressive injury. Adult female C57BL/6 mice were subjected to laminectomy and spinal cord compression using a vascular clip. Inosine or saline injections were administered intraperitoneally, with the first dose performed 24 h after injury and daily for 7 days after injury. The mice were evaluated using Basso Mouse Scale (BMS), locomotor rating scale, and pinprick test for 8 weeks. At the end, the animals were anesthetized and euthanized, and the spinal cords were collected for morphological evaluation. Inosine-treated animals presented better results in the immunostaining for oligodendrocytes and in the number of myelinated fibers through semithin sections compared to saline-treated animals, showing that there was a greater preservation of the white matter. Analysis of the immunoreactivity of astrocytes and evaluation of the inflammatory profile with macrophage labeling revealed that the animals of the inosine group had a lower immunoreactivity when compared to control, which suggests a reduction of the glial scar and less inflammation, respectively, leading to a more favorable microenvironment for spinal cord regeneration. Indeed, inosine-treated animals scored higher on the BMS scale and presented better results on the pinprick test, indicating that the treatment contributed to motor and sensory recovery. After the animals were sacrificed, we obtained the electroneuromyography, where the inosine group showed a greater amplitude of the compound muscle action potential. These results indicate that inosine contributed to the regeneration process in the spinal cord of mice submitted to compressive injury and should be further investigated as a candidate for SCI therapy.

肌苷能改善小鼠脊髓损伤后的功能恢复和细胞形态学。
脊髓损伤(SCI)是中枢神经系统最严重的疾病之一,会导致运动和感觉障碍,严重影响生活质量。以往的研究表明,肌苷可以促进脊髓损伤后的再生。在此,我们研究了肌苷对压迫性损伤后行为和形态学恢复的影响。成年雌性 C57BL/6 小鼠接受椎板切除术,并使用血管夹压迫脊髓。腹腔注射肌苷或生理盐水,第一次剂量在损伤后 24 小时内注射,并在损伤后 7 天内每天注射一次。使用巴索小鼠量表(BMS)、运动评分量表和针刺试验对小鼠进行为期8周的评估。最后,动物被麻醉并安乐死,收集脊髓进行形态学评估。与生理盐水处理的动物相比,肌苷处理的动物在少突胶质细胞免疫染色和半切片髓鞘纤维数量方面的结果更好,这表明白质得到了更好的保护。通过分析星形胶质细胞的免疫活性和用巨噬细胞标记评估炎症特征,发现肌苷组动物的免疫活性比对照组低,这分别表明胶质瘢痕减少和炎症减轻,从而为脊髓再生创造了更有利的微环境。事实上,肌苷处理的动物在BMS量表中得分更高,在针刺试验中结果更好,这表明肌苷处理有助于运动和感觉的恢复。动物被处死后,我们对其进行了电神经肌电图检查,结果显示肌苷组的复合肌动作电位振幅更大。这些结果表明,肌苷有助于压迫性损伤小鼠脊髓的再生过程,应将其作为 SCI 治疗的候选药物进行进一步研究。
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来源期刊
CiteScore
2.40
自引率
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