Soares Dos Santos Cardoso Fellipe, Cardoso Ricardo, Dos Santos Ramalho Bruna, Bastos Taboada Tiago, Dos Santos Nogueira Ana Carolina, Blanco Martinez Ana Maria, Martins de Almeida Fernanda
Laboratório de Neurodegeneração e Reparo, Departamento Anatomia Patológica, Hospital Universitário Clementino Fraga Filho HUCFF/UFRJ, Brazil.
Laboratório de Neurodegeneração e Reparo, Departamento Anatomia Patológica, Hospital Universitário Clementino Fraga Filho HUCFF/UFRJ, Brazil; Instituto de Ciências Biomédicas, ICB/UFRJ, Brazil.
Neuroscience. 2019 Dec 15;423:206-215. doi: 10.1016/j.neuroscience.2019.09.023. Epub 2019 Nov 1.
Trauma to the peripheral nervous system (PNS) results in loss of motor and sensory functions. After an injury, a complex series of events begins, allowing axonal regeneration and target reinnervation. However, this regenerative potential is limited by several factors such as age, distance from the lesion site to the target and severity of lesion. Many studies look for ways to overcome these limitations. Inosine, a purine nucleoside derived from adenosine, emerges as a potential treatment, due to its capacity to regulate axonal growth, neuroprotection and immunomodulation, contributing to motor recovery. However, no studies demonstrated their effects on PNS. C57/Black6 mice were submitted to sciatic nerve crush and received intraperitoneal injections of saline or inosine (70 mg/kg), one hour after injury and daily for one week. To evaluate axonal regeneration and functional recovery, electroneuromyography, Sciatic Function Index (SFI), rotarod and pinprick tests were performed. Our results showed that the inosine group presented a higher number of myelinated fibers and a large amount of fibers within the ideal G-ratio. In addition, the results of electroneuromyography showed greater amplitude of the compound muscle action potentials in the first and second weeks, suggesting anticipation of regeneration in the inosine group. We also observed in the inosine group, motor and sensory neurons survival, reduction in the number of macrophages and myelin ovoids in the sciatic nerves, and an early recovery of motor and sensory functions. Thus, we conclude that the use of inosine accelerates axonal regeneration promoting an early recovery of motor and sensory functions.
外周神经系统(PNS)损伤会导致运动和感觉功能丧失。损伤后,一系列复杂的事件开始发生,促使轴突再生和靶标重新神经支配。然而,这种再生潜力受到多种因素的限制,如年龄、损伤部位与靶标的距离以及损伤的严重程度。许多研究都在寻找克服这些限制的方法。肌苷是一种由腺苷衍生而来的嘌呤核苷,由于其具有调节轴突生长、神经保护和免疫调节的能力,有助于运动恢复,因而成为一种潜在的治疗方法。然而,尚无研究证明其对外周神经系统的作用。将C57/Black6小鼠的坐骨神经进行挤压,并在损伤后1小时腹腔注射生理盐水或肌苷(70mg/kg),连续注射一周。为了评估轴突再生和功能恢复情况,进行了神经肌电图、坐骨神经功能指数(SFI)、转棒试验和针刺试验。我们的结果表明,肌苷组有更多的有髓纤维,且大量纤维的G比值处于理想范围内。此外,神经肌电图结果显示,在第一周和第二周,复合肌肉动作电位的幅度更大,这表明肌苷组的再生提前。我们还观察到,在肌苷组中,运动和感觉神经元存活,坐骨神经中巨噬细胞和髓鞘卵圆体数量减少,运动和感觉功能早期恢复。因此,我们得出结论,使用肌苷可加速轴突再生,促进运动和感觉功能的早期恢复。