Temporary Sensory Protection of Denervated and Skeletal Muscle: A Quantitative Ultrastructural and Functional Assessment of Nerve and Muscle

Abstract

<p>Peripheral nerve injuries have a devastating impact on muscle function due to the distance the axons must regenerate to reinnervate the target muscle. By the time the axons reinnervate the muscle, it has strophied and lost itself receptiveness resulting in impaired function. The objective of this study was to answer the following questions: 1. Do sensory axons delay muscle atrophy following denervation? 2. Does the protective effect observed by sensory axons translate into restored muscle function? 3. Do sensory axons preserve the architecture of the distal nerve sheath and provide a favourable regeneration substrate? 4. Do sensory axons influence the trophic effect on denervated muscle to maintain its "receptiveness" to reinnervation? Following tibial nerve transection, rats were assignedd to one of the following groups: (1) saphenous to distal tibial nerve neurorrhaphy (Nerve-to-Nerve sensory protected (SP)); (2) saphenous to gastrocnemius neurotization (Nerve-to-Muscle sensory protected (SP) in the absence of the distal nerve sheath); (3) Unprotected controls (tibial nerve transection) or, (4) immediate common peroneal to tibial nerve neurorrhaphy (Immediate Repair with a motor nerve). The unoperated contralateral leg of treated animals served as a control. After a 6-month denervation period followed by motor reinnervation, ultrastructure, histology, morphometrics of nerve and muscle were assessed and muscle function was measured. Specimens of distal tibial nerve in the Nerve-to-Nerve (SP) group were superior to Unprotected controls shown by a significant increase in axon density, a significant decrease in collagen area, and improved axon-to-Schwann cell coupling. These features are characteristic of the original neural environment and reflect sustained neural integrity. Although axon number in the Nerve-to-Nerve (SP) group was similar to the Nerve-to-Muscle (SP) group, improved regeneration was evident in the Nerve-to-Nerve (SP) group shown by several axons at various stages of myelination, in a "normal" one-to-one association with a Schwann cell. The Nerve-to-Nerve (SP) group also displayed a significant increase in mean axon area than the Nerve-to-Muscle (SP) group. Gastrocnemius muscle specimens from both sensory protected groups displayed less collagenization and fat deposition than Unprotected control muscle, similarity in mean total muscle fibre size, and evidence of reinnervation (fibre type grouping) among regions of "mosaicism" suggesting a preservation of normal muscle features. Fast twitch fibres predominated in both sensory-protected groups (60% to 40%) as in normal muscle. Unprotected controls contained no fast twitch fibres and the total muscle fibre area of this group was significantly smaller than all other experimental groups. The man area of fast twitch fibres in Nerve-to-Muscle (SP) group was significantly larger than the Nerve-to-Nerve (SP) group was suggesting a possible trophic influence on fast twitch muscle fibre area. Mean compound muscle action potential amplitude in the Nerve-to-Nerve (SP) group was significantly higher than the Nerve-to-Muscle (SP) and Unprotected control groups. Although the Nerve-to-Muscle (SP) group demonstrated a significantly higher isometric contractile twitch force than Unprotected controls, this as only slightly increased possibly due to the unusually high values for the Unprotected controls. These findings suggest that a feasible method to optimally diminish the denervation changes in muscle is to preserve the architecture of the distal nerve and concomitantly maintain the trophic influence on the muscle fibres.</p>