College of Pharmacy, University of Al-Ameed, Karbala, Iraq.
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences (ArUMS), Ardabil, Iran.
Fundam Clin Pharmacol. 2023 Feb;37(1):107-115. doi: 10.1111/fcp.12827. Epub 2022 Aug 28.
Peripheral nerve injuries (PNI/s) are common orthopedic conditions, characterized by motor and sensory deficits in the damaged region. There is growing evidence that the L-type calcium channel antagonist nimodipine has neuroprotective and neuroregenerative effects in animal models of neurological disorders. The efficacy of nimodipine on improving motor function and sensation following a sciatic nerve crush model was investigated in male Wistar rats as a model of PNI. At different time periods following damage, we evaluated motor function, sensory recovery, electrophysiology, histomorphometry, and gene expression. Moreover, we used histological and mass ratio analysis of the gastrocnemius muscle to assess atrophy. Our findings suggest that the nimodipine improves motor and sensory function more quickly in the damaged region 2, 4, and 6 weeks after 1 week of treatment. Nimodipine treatment also increased the number of myelinated fibers while decreasing their thickness, as shown by histomorphometry. Additionally, nimodipine treatment increases the mRNA levels of neurotrophic factors (BDNF and NGF), which are known to contribute to the regeneration of injured neurons. The impact of nimodipine in PNI recovery may be due to its stimulation of the CREB signaling pathway and suppression of pro-inflammatory factor production.
周围神经损伤(PNI/s)是常见的骨科疾病,其特征是受损区域的运动和感觉功能丧失。越来越多的证据表明,L 型钙通道拮抗剂尼莫地平在神经病变动物模型中具有神经保护和神经再生作用。本研究以坐骨神经挤压模型大鼠为 PNI 模型,探讨了尼莫地平对改善运动功能和感觉恢复的作用。在损伤后不同时间点,我们评估了运动功能、感觉恢复、电生理学、组织形态计量学和基因表达。此外,我们还使用腓肠肌的组织学和质量比分析来评估萎缩。我们的研究结果表明,尼莫地平在损伤后 1 周治疗 2、4 和 6 周时,更快地改善了损伤区域的运动和感觉功能。组织形态计量学显示,尼莫地平治疗还增加了有髓神经纤维的数量,同时减少了其厚度。此外,尼莫地平治疗还增加了神经营养因子(BDNF 和 NGF)的 mRNA 水平,这些因子已知有助于损伤神经元的再生。尼莫地平在 PNI 恢复中的作用可能与其对 CREB 信号通路的刺激和对促炎因子产生的抑制有关。