Department of Neurology, Spinal Cord Injury Medicine (Paraplegiology), The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
Department of Neuromuscular Diseases, Institute of Neurology, University College London, London, WC1N 3BG, UK.
Sci Rep. 2019 Nov 13;9(1):16699. doi: 10.1038/s41598-019-53235-w.
Sensitive and objective biomarkers of neuronal injury, degeneration, and regeneration can help facilitate translation of experimental findings into clinical testing. Whereas measures of upper motor neuron connectivity have been readily established, functional assessments of lower motor neuron (LMN) innervation of forelimb muscles are lacking. Compound muscle action potential (CMAP) and motor unit (MU) number estimation (MUNE) are well-established methods that allow longitudinal MU integrity monitoring in patients. In analogy we refined CMAP and MUNE methods for assessing spinal MU input in the rat forelimb and hindlimb. Repeated CMAP and MUNE recordings are robust (coefficients of variability: 4.5-11.3%), and MUNE measurements from forelimb wrist flexor muscles (415 ± 8 [SEM]) align with back-traced anatomical LMN counts (336 ± 16 [SEM]). For disease validation, cross-sectional blinded electrophysiological and muscle contractility measurements were obtained in a cohort of G93A SOD1 mutant overexpressing rats and compared with controls. Longitudinal assessment of mutant animals demonstrated progressive motor unit decline in the hindlimb to a greater extent than the forelimb. Hindlimb CMAP and MUNE demonstrated strong correlations with plantarflexion muscle contractility. Cross-species assessment of upper/fore- limb and lower/hind- limb motor units using objective electrophysiological CMAP and MUNE values as biomarkers will guide and improve bi-directional translation.
敏感和客观的神经元损伤、退化和再生生物标志物有助于将实验发现转化为临床测试。虽然已经建立了上运动神经元连接的测量方法，但缺乏对前肢肌肉下运动神经元（LMN）支配的功能评估。复合肌肉动作电位（CMAP）和运动单位（MU）数量估计（MUNE）是成熟的方法，可以在患者中进行纵向 MU 完整性监测。类似地，我们改进了用于评估大鼠前肢和后肢脊髓 MU 输入的 CMAP 和 MUNE 方法。重复的 CMAP 和 MUNE 记录具有稳健性（变异系数：4.5-11.3%），并且来自前肢腕屈肌的 MUNE 测量值（415±8[SEM]）与回溯解剖学 LMN 计数（336±16[SEM]）一致。为了验证疾病，在一组过表达 G93A SOD1 突变体的大鼠中进行了横断面盲法电生理和肌肉收缩力测量，并与对照组进行了比较。对突变动物的纵向评估表明，后肢的运动单位比前肢更明显地下降。后肢 CMAP 和 MUNE 与跖屈肌收缩力有很强的相关性。使用客观电生理 CMAP 和 MUNE 值作为生物标志物对上肢/前肢和下肢/后肢运动单位进行跨物种评估，将指导和改善双向转化。
