Muscle Spindle Alterations Following Ischemic Stroke and Peripheral Denervation in Murine Models

Proprioceptive dysfunction is a common rehabilitation issue in neurological injury, and the muscle spindle (MS) is considered a critical structure in this dysfunction. The present study aimed to investigate the morphological alterations of MS in two classical neurological diseases: denervation and stroke, and to understand the role of MS in these two diseases preliminarily. The denervation and stroke model animals were constructed by using a surgical operation and middle cerebral artery occlusion (MCAO) protocol, respectively. The muscles from the affected-side limb and the healthy-side limb were harvested and then fixed, embedded, sliced, stained, and subjected to other laboratory analysis at the predetermined time point. The capsule thickness, cross-sectional area (CSA) of intrafusal fiber and extrafusal fiber, the collagen area percentage, and the hyaluronic acid were investigated in the denervation and stroke animal model. In denervation rats, the capsule thickness in the denervation-side limb increased significantly with the p value under 0.01, while the CSA of intrafusal fiber and extrafusal fiber both decreased with the p values under 0.01 and 0.0001, respectively, compared to the healthy-side. The collagen area percentage increased on the denervation side, with a p value under 0.01, but no difference was found in hyaluronic acid. In stroke mice, similar tendencies were found in the stroke-affected side regarding the capsule thickness and CSA of intrafusal fiber, but there was no statistical significance. The CSA of extrafusal fiber seems equal on the stroke-affected side and healthy-side as well as the collagen area percentage. The hyaluronic acid in the capsule of MS was higher in affected-side compared to healthy-side with a p value under 0.05. The alterations of MSs suggested that MS's roles in proprioception are diverse in these two typical neurological diseases. The changes of MS in denervation are aligned with the alterations of muscle and intramuscular connective tissue, but are not aligned in stroke, especially the hyaluronic acid. The present study provides a novel MS-based view to understand proprioception dysfunction in stroke and peripheral nerve injury.