Nimodipine Promotes Functional Recovery After Spinal Cord Injury in Rats.

Song Zhang,Xiaolong Zheng,Ruoying Zhang,Ziyu He,Hong Chen,Minghuan Wang,Fangliang Guo,Wei Wang

doi:10.3389/fphar.2021.733420

Song Zhang, Xiaolong Zheng + Show 6 more

Open Access

https://doi.org/10.3389/fphar.2021.733420

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Abstract

Spinal cord injury (SCI) is a devastating condition that results in severe motor, sensory, and autonomic dysfunction. The L-/T-type calcium channel blocker nimodipine (NMD) exerts a protective effect on neuronal injury; however, the protective effects of long-term administration of NMD in subjects with SCI remain unknown. Thus, the aim of this study was to evaluate the role of long-term treatment with NMD on a clinically relevant SCI model. Female rats with SCI induced by 25 mm contusion were subcutaneously injected with vehicle or 10 mg/kg NMD daily for six consecutive weeks. We monitored the motor score, hind limb grip strength, pain-related behaviors, and bladder function in this study to assess the efficacy of NMD in rats with SCI. Rats treated with NMD showed improvements in locomotion, pain-related behaviors, and spasticity-like symptoms, but not in open-field spontaneous activity, hind limb grip strength or bladder function. SCI lesion areas and perilesional neuronal numbers, gliosis and calcitonin gene-related peptide (CGRP+) fiber sprouting in the lumbar spinal cord and the expression of K+–Cl− cotransporter 2 (KCC2) on lumbar motor neurons were also observed to further explore the possible protective mechanisms of NMD. NMD-treated rats showed greater tissue preservation with reduced lesion areas and increased perilesional neuronal sparing. NMD-treated rats also showed improvements in gliosis, CGRP+ fiber sprouting in the lumbar spinal cord, and KCC2 expression in lumbar motor neurons. Together, these results indicate that long-term treatment with NMD improves functional recovery after SCI, which may provide a potential therapeutic strategy for the treatment of SCI.

Highlights

Spinal cord injury (SCI) is a devastating condition that leads to severe problems involving impaired motor, sensory, and autonomic functions (Ahuja et al, 2017)
Previous studies indicate that NMD exerts a protective effect on neuronal injury and prevents the development of spasticity after SCI (Tator et al, 2012; Marcantoni et al, 2020)
Long-term administration of calcium channel blockers may lead to muscle weakness (Zamponi et al, 2015); we monitored the hind limb grip strength prior to injury and from week 6 to week 12 post-SCI

Summary

Introduction

Spinal cord injury (SCI) is a devastating condition that leads to severe problems involving impaired motor, sensory, and autonomic functions (Ahuja et al, 2017). Approaches that mitigate secondary injury after SCI may lead to better functional improvement (Silva et al, 2014; Ahuja et al, 2016). The sample size in the clinical trial might have been too small to detect a significant clinical effect (Pointillart et al, 2000). Based on these observations, long-term administration of NMD after SCI may improve function. This study aims to evaluate the efficiency of long-term therapy with NMD in a clinically relevant SCI model

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