Impact of volumetric muscle loss injury on persistent motoneuron axotomy

Introduction: Volumetric muscle loss (VML) occurs following significant traumatic injury or surgical removal of skeletal muscle, resulting in nonrecoverable loss of tissue and long-term dysfunction. Perhaps less recognized is that VML injuries inherently disrupt the neuromuscular unit, resulting in fiber denervation and presumptive motor unit rearrangement, expansion, and/or loss. To characterize neural dysfunction we quantified motoneuron axotomy, in efforts to understand how this relates to the temporal coordination of neuromuscular and morphological alterations due to injury. Methods: In an established rat tibialis anterior (TA) VML injury model, we examined the motoneuron, skeletal muscle, and maximal isometric torque at 3, 7, 14, and 21 days postinjury. Results: Significant axotomy of 57-79% of all TA muscle motoneurons was observed through 21 days postinjury, which was coupled with a 45-90% TA maximal torque deficit. Discussion: A ∼20% partial ablation of the TA muscle causes disproportionate damage across the motor unit acutely postinjury.