Donor Nerve Injury Research Articles

Muscle reinnervation in one or two stages?: experimental study in rats with end-to-side nerve graft

PURPOSE: To compare muscle reinnervation in one and two surgical stages using end-to-side neurorrhaphy (ESN) without donor nerve injury. METHODS: The experiment was performed on four groups of 20 rats. Group 1 (G1), one stage, received the graft which was sutured to the tibial nerve, with ESN, and its free stump was sutured end-to-end to the distal stump of the sectioned peroneal nerve (PN), all in the same operation. In Group 2 (G2), two stages, the nerve graft was sutured to the tibial nerve, with ESN. Two months later the PN was sectioned and its distal stump connected to the distal stump of the graft as in G1. Normal control group (Gn) received the graft only sutured to the tibial nerve, with ESN. Denervated control group (Gd), as well received the graft and had the PN sectioned and its two stumps buried in adjacent musculature, with the aim of denervating the cranial tibial muscle (CTM), the target of this study. The parameters used to evaluate CTM reinnervation were muscle mass, muscle fiber's minimum diameter and area. RESULTS: The mean CTM mass, the average of the muscular fibers areas and the average of the muscular fiber minimum diameters was higher (all p<0.0001) in G2 than in G1. Comparing the four groups, these parameters had their maximum expression in Gn and the minimum in Gd, as expected. CONCLUSION: The two stages showed better muscle reinnervation than one stage.

Morphological assessment of early axonal regeneration in end-to-side nerve coaptation models

Histological changes were observed in peripheral nerves following end-to-side nerve coaptation to determine the effects of perineurial opening and deliberate donor nerve injury during surgery. Twenty rats were randomised into four groups as follows: group 1, end-to-side nerve coaptation without perineurial opening; group 2, end-to-side nerve coaptation with simple perineurial opening; group 3, end-to-side nerve coaptation with partial crush injury after perineurial opening; group 4, end-to-side nerve coaptation with partial neurotomy after perineurial opening. Seven days after coaptation of the musculocutaneous (recipient) nerve to the ulnar (donor) nerve, the nerves were immunohistochemically analysed using antibodies against neurofilament-H (RT97) and phosphorylated GAP-43 (p-GAP-43). The former labels all axons, including regenerating axons and degenerated axonal debris, while the latter only labels regenerating axons. Results demonstrated no regenerating nerves in the recipient nerve of group 1. In group 2, because nerve herniation from the perineurial opening partially injured donor nerve fibres, some regenerating axons extended proximally and distally along the partially injured fibres in the donor nerve; some of these regenerating axons also extended into the recipient nerve via the perineurial opening. In groups 3 and 4, thin regenerating axons were more prominent in recipient and donor nerves compared with group 2. Statistical evaluation revealed increased efficacy of perineurial opening and deliberate donor nerve injury in end-to-side nerve coaptation, suggesting that partial nerve fibre herniation with partial axonotmesis or neurotomesis was important for effective axonal regeneration in end-to-side nerve coaptation.

The origin of regenerating axons after end-to-side neurorrhaphy without donor nerve injury

The purpose of this study was to determine the origins of regenerated axons after end-to-side neurorrhaphy (ETSN) without donor nerve injury by comparing the time of appearance of regenerating axons for proximally coapted ETSN and distally coapted ETSN. Thirty rabbits were used in each group. In the proximal ETSN group, the ulnar nerve was transected and the distal end sutured to the median nerve 3cm above the elbow joint, whereas in the distal ETSN group, it was 3cm below the elbow joint. Coaptation was performed by wrapping the aponeurosis of nearby muscle. Observations were made weekly for 6 weeks after ETSN. Axonal regeneration was studied by morphometric analysis and immunohistochemistry. The times of appearance of regenerating axons differed in the proximal and distal ETSN groups. Axonal densities in proximal segments of donor nerves continuously increased and the axonal diameters of proximal segments of donor nerves continuously decreased with time after ETSN. Our findings suggest that regenerated axons after ETSN without donor nerve injury originate from the central nervous system rather than coaptation sites.

Effect of Acetyl-L-Carnitine on Axonal Sprouting Following Donor Nerve Injury Distal to an End-to-Side Neurorrhaphy Model

This study investigated the hypothesis that acetyl-L-carnitine (ALCAR) could have a significant effect on nerve regeneration after end-to-side neurorrhaphy. The ability of the ALCAR to enhance nerve regeneration in combination with various types of donor nerve injury distal to the coaptation site was also determined. Twenty-five Sprague-Dawley rats were randomized to five groups of five animals each, in which three different types of donor injury (crush, ligation, and transection injury) distal to the coaptation site were executed (groups C, D, and E, respectively). Animals in group A (placebo) and group B underwent a standard end-to-side neurorrhaphy. Animals from groups B to E received a daily intraperitoneal injection of 50 mg/kg/d of ALCAR, and a placebo was injected in place of ALCAR in animals in group A. Administration of acetyl-L-carnitine alone did not prove to be a significant stimulus for regeneration, as concluded after comparison among the two noninjury models of the donor nerve (groups A and B). Indeed, the combination of an injury model of the donor nerve (crush injury) with administration of acetyl-L-carnitine proved to be a significantly more potent stimulus for regeneration than the control (placebo) group, as measured by behavioral, muscle morphometric, electrophysiological, and histomorphometric studies.

Effect of Donor Nerve Injury Distal to an End-to-Side Neurorrhaphy Model

In end-to-side neurorrhaphy, "noninjury" models of the donor nerve do not seem to offer worthwhile functional outcomes. The role of donor nerve injury distal to the coaptation site remains unclear. End-to-side neurorrhaphy was studied in a rat model in which the proximal stump of the transected musculocutaneous nerve was sutured to the median nerve by end-to-side coaptation. Twenty Sprague-Dawley rats were randomized to four groups of five animals each, in which three different types of donor injury (crush, ligation, or transection injury) distal to the coaptation site were executed; findings were compared with a similar end-to-side model without donor nerve injury (control). Behavioral analysis, electrophysiological studies, muscle morphometric studies, and nerve fibers counts showed no significant differences among groups. However, there was a significant difference regarding mean myelin area (P = 0.0362) and mean fiber diameter (P = 0.0159) for the crush injury group as compared with the control group. No significant differences were found among the other groups. These data suggest that donor crush injury distal to the coaptation site may increase the rate of myelin formation in regenerating axons across an end-to-side model; however, at 4 weeks of follow-up, there was no significant behavioral or functional significance in this treatment group.

Motor Neuron Regeneration through End-to-Side Repairs Is a Function of Donor Nerve Axotomy

Over the past decade, a growing body of literature has emerged supporting the use of end-to-side (terminolateral) neurorrhaphy for the treatment of selected peripheral nerve injuries. It remains unclear, however, whether injury to the donor nerve is necessary to achieve significant regeneration through such repairs. End-to-side repair was studied in a rodent model in which the terminal limb of a transected peroneal nerve was sutured to the lateral aspect of the tibial nerve. Twenty-eight Lewis rats were randomized to four groups of seven animals each corresponding to incrementally greater donor nerve injuries as follows: group 1, conventional end-to-side neurorrhaphy; group 2, end-to-side neurorrhaphy with proximal crush injury; group 3, end-to-side neurorrhaphy with neurotomy; and group 4, end-to-end repair of transected peroneal nerve (positive control). At 12 weeks, retrograde labeling of cell bodies of the ventral horn demonstrated significant differences between experimental groups, with mean counts in group 4 (1237 +/- 171) > group 3 (522 +/- 204) > group 2 (210 +/- 132) > or = group 1 (126 +/- 146). This association between nerve injury and motor neuron counts was closely mirrored in quantitative assessments of peripheral nerve regeneration and normalized wet muscle masses. These data support the hypothesis that donor nerve injury is a prerequisite for significant motor neuronal regeneration across end-to-side repairs. Motor neuron regeneration through end-to-side repairs is optimized by deliberate transection of donor nerve axons.

Role of Age and Donor Nerve Injury as Determinants of Regeneration across End-to-Side Nerve Repairs

End-to-side neurorrhaphy is indicated when a proximal nerve stump is unavailable due to trauma, surgical resection, or disease. A growing body of literature supports the use of end-to-side nerve repairs for the treatment of peripheral nerve injuries. However, the key determinants of functional outcome remain largely unknown. It was hypothesized that donor nerve injury and younger age would both favor enhanced nerve regeneration. The reported experiment tested these hypotheses across a spectrum of donor nerve injury and animal age.

Impact of epineurial excision of the distal recipient nerve in terminolateral neurorrhaphy.

Different surgical modifications were studied to improve success in terminolateral neurorrhaphy. The authors evaluated the efficacy of distal epineurial excision of the recipient nerve stump. Forty male Wistar rats were evaluated in four groups. The right hind limbs of the animals were used as experimental limbs and the left hind limbs as control limbs. The peroneal nerve was transected at a level 1 cm above the bifurcation of the tibial nerve. The proximal stump of the peroneal nerve was covered with gluteus maximus muscle fibers in all groups. In Group 1, the distal peroneal nerve was not processed and was left in the operative field. In Group 2, the distal peroneal nerve stump was sutured to an epineurial window on the tibial nerve by epineurial neurorrhaphy. In Group 3, the distal stump of the peroneal nerve was buried in the tibial nerve without epineurial resection, and in Group 4 with a 1-mm epineurial excision. Walking track analyses, electromyographic studies, and histomorphometric analyses were performed after a 3-month follow-up period. Statistical analysis was done with ANOVA and Tukey tests. No important donor-nerve injury was detected. Axonal regeneration and functional results were better in Group 4 compared to Groups 2 and 3. An increased donor and recipient nerve contact surface area with the excision of the epineurium from the distal peroneal nerve stump (Group 4) might provide superior results with longer follow-up periods.