Study evaluated the feasibility and robustness of compound muscle action potential (CMAP) and motor unit (MU) number estimation (MUNE) recording techniques in the wild type rat forelimb and hindlimb through repeated measurements to determine mean values and test-retest reliability. CMAP and MUNE are well-established methods that allow longitudinal MU integrity monitoring in patients. The study assessed whether their electrophysiological estimates reasonably align with spinal cord anatomy by comparing electrophysiologically-calculated MU numbers with motor neuron counts determined by retrograde anatomical tracer analysis. Lastly, the study examined the validity of CMAP and MUNE as sensitive objective biomarkers of longitudinal motor unit degeneration and dysfunction by obtaining repeated recordings from SOD1 transgenic rats, which model amyotrophic lateral sclerosis (ALS). In analogy, the authors 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 percent), and MUNE measurements from forelimb wrist flexor muscles align with back-traced anatomical LMN counts. For disease validation, cross-sectional blinded electrophysiological and muscle contractility measurements were obtained in 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. The ability of forelimb and hindlimb MUNE to objectively quantify MU integrity will facilitate clinically relevant advances in rat models of spinal cord and neuromuscular disease.
Author(s):
Harrigan, Markus E. |Filous, Angela R. |Tosolini, Andrew P. |Morris, Renee |Schwab, Jan M. |Arnold, W. David|
