Terminolateral neurorrhaphy: a review of the literature.

Terminolateral neurorrhaphy (TLN) is an experimental technique for repairing peripheral nerves, when the proximal cut nerve stump is not available for traditional end-to-end repair. Over the past 7 years, the efficacy of TLN, its ability to preserve donor nerve function, the necessity of disrupting donor nerve connective tissue layers during the procedure, the mechanism by which TLN affords reinnervation, and the definition of the procedure, have been debated. In this critical review of TLN literature, the authors attempt to demonstrate 1) that a TLN in which the surgeon deliberately transects donor nerve axons is an effective method for peripheral nerve repair; the mechanisms by which axons innervate target muscles following this procedure are well-defined, and there is adequate experimental and clinical evidence to support its clinical application; and 2) that a TLN procedure in which the surgeon attempts to leave the donor nerve intact is neither mechanistically distinct from a TLN with deliberate donor nerve axotomy, nor is it as efficacious. Future studies should assess the degree of donor nerve transection that will maximize reinnervation via the TLN graft, without incurring functionally significant donor nerve deficits.

"Donor" muscle structure and function after end-to-side neurorrhaphy.

End-to-end nerve coaptation is the preferred surgical technique for peripheral nerve reconstruction after injury or tumor extirpation. However, if the proximal nerve stump is not available for primary repair, then end-to-side neurorrhaphy may be a reasonable alternative. Numerous studies have demonstrated the effectiveness of this technique for muscle reinnervation. However, very little information is available regarding the potential adverse sequelae of end-to-side neurorrhaphy on the innervation and function of muscles innervated by the "donor" nerve. End-to-side neurorrhaphy is hypothesized to (1) acutely produce partial donor muscle denervation and (2) chronically produce no structural or functional deficits in muscles innervated by the donor nerve. Adult Lewis rats were allocated to one of two studies to determine the acute (2 weeks) and chronic (6 months) effects of end-to-side neurorrhaphy on donor muscle structure and function. In the acute study, animals underwent either sham exposure of the peroneal nerve (n = 13) or end-to-side neurorrhaphy between the end of the tibial nerve and the side of the peroneal nerve (n = 7). After a 2-week recovery period, isometric force (F(0) was measured, and specific force (sF(0) was calculated for the extensor digitorum longus muscle ("donor" muscle) for each animal. Immunohistochemical staining for neural cell adhesion molecule (NCAM) was performed to identify populations of denervated muscle fibers. In the chronic study, animals underwent either end-to-side neurorrhaphy between the end of the peroneal nerve and the side of the tibial nerve (n = 6) or sham exposure of the tibial nerve with performance of a peroneal nerve end-to-end nerve coaptation approximately 6), to match the period of anterior compartment muscle denervation in the end-to-side neurorrhaphy group. After a 6-month recovery period, contractile properties of the medial gastrocnemius muscle ("donor" muscle) were measured. Acutely, a fivefold increase in the percentage of denervated muscle fibers (1 +/0 0.7 percent to 5.4 +/-2.7 percent) was identified in the donor muscles of the animals with end-to-side neurorrhaphy (p < 0.001). However, no skeletal muscle force deficits were identified in these donor muscles. Chronically, the contractile properties of the medial gastrocnemius muscles were identical in the sham and end-to-side neurorrhaphy groups. These data support our two hypotheses that end-to-side neurorrhaphy causes acute donor muscle denervation, suggesting that there is physical disruption of axons at the time of nerve coaptation. However, end-to-side neurorrhaphy does not affect the long-term structure or function of muscles innervated by the donor nerve.

Termino-lateral neurorrhaphy: the functional axonal anatomy.

The goal of this study was to determine the functional axonal anatomy of a termino-lateral neurorrhaphy (TLN). We hypothesize that axons populating a TLN must relinquish functional connections with their original targets prior to establishing new connections via the TLN. Two-month-old F344 rats underwent a TLN between the left peroneal nerve and a nerve graft tunneled to the contralateral hindlimb. Three months postoperatively, an end-to-end neurorrhaphy was performed between the nerve graft and the right peroneal nerve. Four months after the second operation, contractile properties and electromyographic (EMG) signals were measured in the bilateral hindlimbs. Left peroneal nerve stimulation proximal to the TLN site resulted in bilateral extensor digitorum longus (EDL) and tibialis anterior (TA) muscle contractions, with significantly lower forces on the side reinnervated by TLN. Evoked EMGs demonstrated that the right and left hindlimb musculature were electrically discontinuous following TLN. These data support our hypothesis that axons can form functional connections via a TLN, but they must first relinquish functional connections with their original targets.

Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury.

To gain insight into the role that transforming growth factor-beta 1 (TGF-beta 1) plays in the regeneration of kidneys following acute renal failure, we characterized the expression of TGF-beta 1 mRNA and the expression of active and latent TGF-beta peptide at various times during recovery from acute ischemic injury in rat. Levels of whole kidney TGF-beta 1 mRNA were elevated significantly at 12 h postinjury (1.5-fold vs. sham-operated controls), and by 24 h postinjury were elevated by 3.6-fold. Levels remained elevated for 14 days following ischemia, but were no longer elevated at 28 days postinjury. In situ hybridization demonstrated that the elevated expression of TGF-beta 1 was localized predominantly to cells in the regenerating tubules in the outer medulla. When examined at 14 days postischemia, levels of TGF-beta 1 mRNA were elevated in the outer medulla only in tubules that appeared incompletely regenerated. Immunohistochemical staining localized active TGF-beta to the lumen of proximal tubules in control animals and in desquamated and regenerating tubular epithelial cells following ischemia. TGF-beta 1 latency-associated peptide was present intracellularly in proximal tubules of sham-operated rats and reduced following ischemia. We hypothesize that endogenous renal TGF-beta serves to promote tissue regeneration following acute injury via an autocrine or paracrine mechanism.