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Xavier Navarro

Publications and source records attributed to Xavier Navarro.

40 records · Page 3Linked to original sources

Functional impact of axonal misdirection after peripheral nerve injuries followed by graft or tube repair.

Accuracy of reinnervation is one of the main factors conditioning functional recovery after brain, spinal, or peripheral axonal damage. Using the peripheral nerve as an experimental model, we studied the amount of inaccurate muscle reinnervation and its consequences on walking. Adult rats were submitted to an 8-mm resection of the sciatic nerve repaired by autograft (AG, n = 9), silicone (SIL, n = 13) or poly-L-lactate-epsilon-caprolactone (PLC, n = 11) single guides, and fascicular tubulization of peroneal and tibial branches with a dual silicone tube (FSIL, n = 9). At the end of follow-up, the sciatic nerve and its tibial and peroneal fascicles were dissected and stimulated by means of a suction electrode. In control rats, gastrocnemius and plantar muscles are fully innervated by the tibial fascicle and the tibialis anterior muscle by the peroneal nerve. None of the groups had noticeable recovery of locomotion assessed by the walking track index (SFI around -70 in all groups). After resection, all animals of groups AG, SIL, and PLC showed aberrant muscle reinnervation by axons from a non-corresponding fascicle, whereas in group FSIL only one of six regenerated animals showed misdirected activity. The proportion of inaccurate muscle activation was similar in group AG (47% for gastrocnemius, 54% for tibialis anterior, and 44% for plantar muscles) and in group SIL (42%, 42%, and 42%), and reduced in group PLC (26%, 38%, and 27%). In conclusion, fascicular silicone tubulization allowed the highest degree of accuracy but the lowest recovery, whereas resorbable PLC guides provided for the best balance between amount and accuracy of reinnervation after nerve resection.

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Changes in crossed spinal reflexes after peripheral nerve injury and repair.

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

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Alignment of collagen and laminin-containing gels improve nerve regeneration within silicone tubes.

PURPOSE: Placement of extracellular matrix components has been used as a mean to enhance axonal growth across nerve long gaps repaired by tubulization. However, such matrices may impede axonal regeneration depending on its density and microgeometry. METHODS: Silicone tubes were prefilled with collagen or laminin-containing gels and implanted into a 6 mm gap, a length considered limiting for regeneration, in the mouse sciatic nerve. Gels were polymerized prior to implantation either in horizontal position or subjected to gravitational (in vertical position) or to magnetic forces to induce longitudinal alignment of the fibrils. Recovery of motor, sensory and sudomotor functions in the hindpaw was evaluated during 4 months postoperation. RESULTS: Reinnervation started earlier and achieved slightly higher levels with aligned collagen gels than with the horizontal gel. For the three groups repaired with tubes with Matrigel, there was a gradation of the functional results, reinnervation started earlier and reached higher values in matrix with magnetically-induced, longitudinal orientation than with the horizontal gel, whereas gravitational alignment followed an intermediate evolution. Final morphological evaluation showed more dense residual mass of collagen than of Matrigel at the center of the regenerate nerves. The number of myelinated fibers was increased in tubes with alignment compared to horizontal gels. CONCLUSIONS: Alignment of collagen and laminin gels within a silicone tube increases the success and the quality of regeneration in long nerve gaps. The laminin gel performed better than the collagen gel under each condition tested. The combination of an aligned matrix with embedded Schwann cells should be considered in further steps for the development of an artificial nerve graft for clinical application.

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Improvement of regeneration with predegenerated nerve transplants in silicone chambers.

We compared regeneration and reinnervation of target organs after sciatic nerve resection and repair with silicone tubes filled with saline solution or with a peroneal nerve segment as a nerve transplant versus an autologous sciatic nerve graft leaving either 4 mm or 6 mm gaps. The aims of this study were to evaluate the effects of predegeneration and donor immunogenicity of nerve transplants. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, sensory and motor functions in the hindpaw after three months postoperation for 4 mm and four months postoperation for 6 mm gap groups. Morphometrical analysis of the regenerated nerve were performed at the end of the follow-up. The group with an autograft achieved faster and higher levels of reinnervation for the four functions tested than any of the groups repaired by tubulization. The introduction of a small nerve transplant improved regeneration and reinnervation with respect to a saline solution filled tube slightly with a 4 mm gap, but significantly with a 6 mm long gap. The beneficial effects of the nerve transplant were significantly increased when it was predegenerated, while disappearing when its cellular component was eliminated by repeated freezing. The immunogenicity of the nerve transplant dramatically affected nerve regeneration, as it was impeded by an heterologous transplant in the tube. In summary, the use of silicone chambers with an autologous predegenerated nerve transplant may be an alternative for repairing long gaps in injured nerves, approaching the level of success of an ideal autologous nerve graft.

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