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1.
Regenerating sensory axons of each receptor class make new connections with similar denervated receptors. This study investigates to what extent these axons return to their original receptive field. The lateral cutaneous nerves of the thigh in rats were divided and allowed to regenerate across a 6 mm. gap interposed with frozen and thawed muscle graft towards their original distal nerve stump and a "foreign" sensory nerve, the saphenous nerve. 16 weeks later, myelinated axon counts of 26 pairs of distal nerves showed no preferential growth towards the original receptive field. Lack of topographic specificity during sensory nerve regeneration may explain the faulty localisation of sensation after nerve repair in clinical practice. Following sensory nerve regeneration, the somatosensory cortex receives accurate afferent information but from disparate skin sites; this probably alters the relationship of overlapping sensory fields and may be the cause of distorted pattern recognition.  相似文献   

2.
Axonal regeneration across end-to-side neurorrhaphy has recently been reported; however, neither the mechanism by which collateral sprouting from intact axons is elicited, nor the origin of the regenerating axons are known. There has even been controversy over the presence of collateral axonal sprouting from intact axons altogether. This reported experimental study was designed to clarify these questions. A rat sciatic nerve model was used. To avoid any mechanical damage to the donor nerve during the procedure, a Y-shaped silicone chamber was employed instead of direct suture. Axonal regeneration from the intact tibial nerve across the gap into the peroneal nerve was assessed using a retrograde neurotracer and immunohistochemical staining. Axonal regeneration across the gap was observed in 66 percent of the animals. The neurotracer evaluation clearly showed that all regenerating axons were sensory axons from the dorsal root ganglia. The authors concluded that Schwann cells from the distal wallerian degeneration of nerve segments did elicit collateral axonal sprouting from intact sensory axons, but not from motor axons in end-to-side neurorrhaphy. Invasion of the Schwann cells into the epineurial layer was the crucial step for the initiation of collateral axonal sprouting from the intact axons.  相似文献   

3.
Nerve regeneration, measured as axonal outgrowth, Schwann cell migration, macrophage invasion, and neovascularisation, was compared after repair of a 15 mm gap in rats' sciatic nerves using autologous muscle grafts made acellular either by freezing and thawing or by chemical extraction. Both extracted and freeze-thawed acellular muscle grafts could be used to bridge the defect. However, axons and Schwann cells, as shown by immunohistochemical staining for neurofilaments and S-100 protein, respectively, grew faster into the extracted muscle grafts than into the freeze-thawed acellular muscle grafts and somewhat more axons were observed in the former graft. There were no significant differences between the two graft types with respect to neovascularisation as showed by staining for endothelial alkaline phosphatase, and limited differences concerning invasion of macrophages (ED1 and ED2) as detected by immunocytochemistry. The results showed that chemically extracted muscle grafts could be used to bridge an extended nerve defect and that such grafts in some aspects were superior to freeze-thawed muscle grafts for extended gaps.  相似文献   

4.
Lutz BS  Lidman D 《Microsurgery》2005,25(3):235-240
Mechanical couplers are successfully used for microvascular venous anastomoses. The advantages include a simple and fast technique and a high patency rate. Couplers offer a secluded coaptation site, and might also be of use in peripheral nerve repair. The present study was designed to investigate coupler coaptation of the rat sciatic nerve, evaluating the number and locations of motor and sensory neurons projecting to the selected muscles as well as stimulation-induced muscle contraction force. Adult rats underwent either suture or coupler repair after left sciatic nerve transection. In all rats, the experimental side was compared to the healthy right side. Evaluation after 20 weeks included retrograde labeling of motoneurons and dorsal root ganglion neurons projecting to the tibial anterior muscle and to the tibial posterior muscle, histology, muscle contraction force (tibial anterior muscle and gastrocnemius muscle), and a pinch reflex test. The results show that the suture and the coupler groups did not differ significantly regarding the examined parameters, except for discrete signs of nerve compression at the coaptation site after coupler repair due to fibrous tissue ingrowth. However, this did not impair axonal regeneration. Importantly, axonal outgrowth from the repair site to the surrounding tissue was not observed after coupler coaptation, but it was observed after suture repair. These results suggest that couplers may be of value for repair of nerves in adjacency to avoid axonal crisscrossing between nerves during regeneration.  相似文献   

5.
Nerve regeneration, measured as axonal outgrowth, Schwann cell migration, macrophage invasion, and neovascularisation, was compared after repair of a 15 mm gap in rats' sciatic nerves using autologous muscle grafts made acellular either by freezing and thawing or by chemical extraction. Both extracted and freeze-thawed acellular muscle grafts could be used to bridge the defect. However, axons and Schwann cells, as shown by immunohistochemical staining for neurofilaments and S-100 protein, respectively, grew faster into the extracted muscle grafts than into the freeze-thawed acellular muscle grafts and somewhat more axons were observed in the former graft. There were no significant differences between the two graft types with respect to neovascularisation as showed by staining for endothelial alkaline phosphatase, and limited differences concerning invasion of macrophages (ED1 and ED2) as detected by immunocytochemistry. The results showed that chemically extracted muscle grafts could be used to bridge an extended nerve defect and that such grafts in some aspects were superior to freeze-thawed muscle grafts for extended gaps.  相似文献   

6.
Poor recovery is seen after repair of long defects in peripheral nerves when denatured muscle grafts or regeneration chambers providing physical support alone are used. The presence of Schwann cells and neurotrophic factors is required for axons to migrate significant distances. In this study we have used immunohistochemical techniques and axon counts to quantify the regeneration seen when 5 cm defects in rabbit sciatic nerve were repaired with a composite graft consisting of 2–3 mm lengths of fresh autologous nerve sandwiched between 1 cm frozen-thawed muscle grafts. This technique led to a similar pattern of regeneration as that seen in autologous nerve grafts, used as controls, and a significantly (P<0.0001) greater axonal and Schwann cell regeneration compared with that seen in frozen-thawed muscle grafts of the same total length. In conclusion, we present a simple technique for incorporating a depot of Schwann cells and other essential components into a nerve conduit which has a marked effect on axonal regeneration across long defects. © 1995 Wiley-Liss, Inc.  相似文献   

7.
Summary Background. The efficiency of denatured muscle grafting in nerve repair has been confirmed in experimental models and animals. The first clinical trials to repair digital nerves and mixed sensory-motor nerves were encouraging regarding sensory recovery but motor recovery was poor, probably because of delayed repair. We present the functional outcome of repair of motor nerves using denatured muscle graft and compare the results with those using standard nerve graft techniques. Methods. This prospective study included 9 radial nerve defects repaired with denatured muscle grafts and 23 radial nerve defects repaired using nerve grafts. Missile induced nerve injury, mid-arm level of lesion, a nerve gap smaller than 6 cm, and a preoperative interval of less than 5 months were characteristics shared by all patients. None of the patients had concomitant vascular injury, severe scarring, or significant soft tissue damage in the region of nerve repair. Motor recovery was estimated with 0–5 points, at least 4.7 years after surgery, according to the BMRC scale. Results. A successful outcome (≥M3) was achieved in 7 out of the 9 patients treated using a muscle graft and in 21 out of the 23 patients treated using nerve grafts (P > 0.05). Excellent recovery and the clinically significant re-establishment of thumb extension (M5 grade) were never achieved in the patients treated using muscle grafts. The average motor score was significantly better in patients treated with nerve grafts than in those who received muscle grafts (3.8 ± 0.9 and 3.2 ± 0.8; P = 0.035). With the patients who received muscle grafts, an inverse correlation existed between motor recovery and the length of the nerve gap (P = 0.017). Conclusions. Denatured muscle grafts can be useful for bridging short radial nerve defects, but the quality of recovery is significantly worse than after nerve graft repair. Even if relatively short nerve defects are bridged with denatured muscle grafts, the outcomes correlate inversely with the length of the gap.  相似文献   

8.
The purpose of this study was to evaluate the effects of human recombinant vascular endothelial growth factor (VEGF-165) on peripheral nerve axonal sprouting and elongation following peripheral nerve injury and repair. Two-centimeter nerve gaps were created in rat peroneal nerves and repaired with either peripheral nerve autografts, acellular peripheral nerve isografts, or VEGF-165-treated acellular peripheral nerve isografts. Four months postoperatively, the peroneal nerves were harvested and histomorphometric analysis was performed. The reinnervated extensor digitorum longus (EDL) muscles were harvested and weighed. At the proximal nerve gap coaptation site, there was a statistically significant increase in the total number of axons and percent neural tissue in the VEGF-treated acellular nerve graft group, compared with the acellular peripheral nerve isograft and autograft groups. At the distal coaptation site, however, the total number of axons and percent neural tissue was similar in the acellular and VEGF-treated groups, which was significantly less than the autograft group. VEGF-165 treatment of acellular nerve grafts resulted in greater EDL muscle masses than acellular nerve grafts alone. VEGF treatment of acellular peripheral nerve isografts enhances axonal sprouting, resulting in an increased number of axons and percent neural tissue at the proximal nerve graft coaptation site. In the absence of any cellular elements, VEGF-impregnated acellular peripheral nerve grafts do not demonstrate enhanced axonal elongation, as noted by relatively few axons at the distal nerve graft coaptation site.  相似文献   

9.
Regeneration of the rat sciatic nerve through acellular muscle and nerve autografts was evaluated 6-28 days postoperatively by the sensory pinch test, immunocytochemical staining for neurofilaments, and light and electron microscopy. Data points generated by the pinch test were plotted against postoperative time periods and by the use of regression analysis the initial delay period for muscle grafts was determined to 10.3 days. This value was similar to that previously published for acellular nerve grafts (9.5 days), but significantly longer than that for fresh nerve grafts (3.6 days). The calculated regeneration rate (slope of the regression line) for muscle grafts (1.8 mm/day) did not differ significantly (p > 0.05) from that calculated for acellular nerve grafts (2.1 mm/day) or for fresh nerve grafts (1.5 mm/day). The front of regenerating axons shown by axonal neurofilament staining confirmed the pinch test results. Both types of acellular grafts were repopulated with host non-neuronal cells and the muscle graft contained occasional ectopic muscle fibres. Remnants of graft basal laminae were evident at the ultrastructural level. These results indicate the suitability of either acellular muscle or nerve grafts for nerve repair despite their prolonged initial delay periods compared with conventional fresh nerve grafts.  相似文献   

10.
We examined the influence of misdirection of regenerating motor axons toward the distal sensory Schwann tubes on the muscle contraction force in early nerve repair using a rat sciatic nerve model. At 0, 1, 2, 4 and 8 weeks after severing the tibial, peroneal and sural nerves, the proximal stump of the tibial nerve was anastomosed with the distal stumps of both the peroneal and sural nerves using tubulisation (n=10 in each of five groups). We intentionally used the distal stump of the sural nerve (a sensory nerve) to induce regeneration in motor axons from the proximal tibial nerve stump toward the distal sensory nerve stump. Twenty-four weeks after nerve repair, isometric contraction force and wet weight of the anterior tibial muscle were measured, and the numbers of regenerated myelinated axons (motor and sensory) in the distal sural and peroneal nerves were counted. The rates of sural nerve regeneration were significantly higher at weeks 0 and 1 than at the later repair times. However, muscle contraction force and muscle wet weight did not differ significantly between groups in which nerves were repaired within four weeks of severance. These results indicate that peripheral nerve repair within four weeks of severance does not influence the muscle contraction force of single muscle despite the misdirection of motor axons toward the distal sensory Schwann tubes.  相似文献   

11.
Effects of neurite-promoting factors on rat sciatic nerve regeneration   总被引:1,自引:0,他引:1  
Neurite promoting factors (NPF), fibroblast growth factor, and laminin were instilled inside autologous venous nerve conduits (AVNC) interposed across a 1 cm gap in the rat sciatic nerve. Axonal regeneration was measured electrophysiologically and histologically and was compared to control AVNC and autologous nerve grafts (ANG) in 45 rats. By 1 month, the AVNC group with NPF recovered an average nerve conduction velocity twice that of the ANG group (24 m/sec vs. 12 m/sec). The gastrocnemius muscle action potential of NPF grafts was twice that of the control AVNC and was similar to the ANG (1.63 mV vs. 0.87 mV). In subsequent months, the advantage of NPF disappeared; these grafts were grossly reduced to fibrous bands. Histological examination of these grafts at 5 months revealed a florid intraluminal fibrovascular proliferation, which appeared to be "choking off" the regenerating axons. It is suggested that more refined mixtures of NPF should be instilled inside AVNC so that the improved axonal regeneration is maintained while the late inhibitory fibrosis is avoided.  相似文献   

12.
OBJECT: Rejection of nerve allografts and loss of regenerated host axons after withdrawal of immunosuppressive therapy poses an ongoing challenge in peripheral nerve repair. The present report is of a blinded prospective controlled study in which an established rat model of nerve allotransplantation is used to examine the effect of fiber type on survival and degeneration of nerve allografts after discontinuation of immunosuppression. The authors hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. METHODS: Four-centimeter nerve segments from ACI rats were grafted into peroneal and sural (mixed) or saphenous (sensory) nerve gaps in Lewis rats. In some rats, L4-6 dorsal root ganglia were ablated before grafting, creating pure motor sural and peroneal nerves. All rats received 12 weeks of immunosuppressive therapy to support nerve regeneration into allografts. Immunosuppression with cyclosporin was then withdrawn. At planned death (12-18 weeks postsurgery), graft tissue was subjected to histomorphometric analysis for evaluation of axon survival and loss. Graft rejection led to loss of all axons in approximately 60% of the allograft segments. The mixed nerve group was most prone to complete rejection, with significantly lowered axon counts at Weeks 16 and 18 compared with the Week 12 baseline. Axons from the sensory nerve were least likely to degenerate. The pure motor nerve group axons demonstrated intermediate sensitivity, with a selective loss of larger axons at Week 16 and a significant decrease in axon counts from the Week 12 baseline at Week 18. CONCLUSIONS: Whereas the majority of axons are lost after withdrawal of immunosuppressive therapy from nerve allografts, there is a selective survival of axons from cutaneous sensory nerves and smaller-diameter motor fibers. The biological and molecular mechanisms that make some axons impervious to injury remain to be determined.  相似文献   

13.
Denatured or acellular muscle grafts are known to support axonal regeneration. With increasing gap length, failure of regeneration is evident, due to the lack of viable Schwann cells in the graft. The authors created a biologic nerve conduit, in a rat sciatic nerve model, by implanting cultured Schwann cells into an acellular gracilis muscle. Autologous nerve grafts and acellular muscle grafts without Schwann cells served as controls. After 6 weeks, regeneration was assessed clinically, histologically, and morphometrically. Polymerase chain reaction (PCR) analysis showed that the implanted Schwann cells remained viable within the graft. Good regeneration was noted in the muscle-Schwann cell group, while regeneration in the muscle grafts without Schwann cells was significantly impaired. The muscle-Schwann cell graft demonstrated systematic and organized regeneration, including the proper orientation of regenerated fibers. The number of axons regenerating through the muscle-Schwann cell grafts was significantly increased, compared with the acellular muscle without Schwann cells. Implantation of Schwann cells into acellular muscle thus provided a biologic conduit with large basal lamina tubes, as a pathway for regenerating axons. The positive effects of Schwann cells, producing neurotrophic and neurotropic factors, supported axonal regeneration.  相似文献   

14.
Sensory neurotisation of a muscle (sensory nerve transfer to the motor nerve of a muscle) produces muscle sensibility, but not skin sensibility. How to achieve sensation of a musculocutaneous flap remains a challenge to reconstructive microsurgeons. The purpose of our study was to determine if multiple nerve grafts which were placed vertically between the neuromuscular entrance zone of a muscle and a target area of dermis on the overlying skin could improve sensation. Thirty-six gracilis musculocutaneous flaps (18 rabbits) were raised and divided into three groups: group 1 consisted of 12 sensory neurotised gracilis musculocutaneous flaps with five nerve grafts each; group 2 consisted of another 12 sensory neurotised gracilis flaps with 10 nerve grafts each; and the control group consisted of 12 sensory neurotised gracilis musculocutaneous flaps without any nerve grafts. All nerve grafts spanned the distance between the neuromuscular entrance zone of the gracilis muscle and a specified 3 cm diameter area of the skin island. The saphenous nerve (sensory) was coapted to the obturator nerve (motor nerve of the gracilis) in an effort to achieve improved sensation of the skin island in the musculocutaneous flaps. After 6 months, the flaps were individually evaluated using cortical somatosensory evoked potentials (CSSEP) using normal, painful, cold and hot stimuli. One unoperated rabbit was studied as the baseline CSEEP for comparison. Retrograde horseradish peroxidase (HRP) labelling was then performed to evaluate the possibility of newly established neural pathways. Results of the CSSEP testing revealed that flaps possessing 10 nerve grafts (group 2) demonstrated better sensation when compared to flaps possessing five nerve grafts (group 1) or no nerve grafts (control group). Furthermore, retrograde HRP labelling proved that a new neural pathway had been established from the skin island to the dorsal root ganglia of S1 and S2 via the interposed nerve grafts and the sensory neurotised gracilis muscle in groups 1 and 2 rabbits. The control group did not display any sensory regeneration.  相似文献   

15.
This study investigated the effect of local administration of nerve growth factor-7S (NGF-7S) on the axonal regrowth of mixed peripheral nerves through inside-out vein grafts. Sixty male Wistar rats were randomized into two groups (n = 30). A defect 12 mm long in the right sciatic nerve was created and repaired with an inside-out vein graft from the right jugular vein. NGF-7S (group A) or phosphate-buffered saline (group B; control) was locally administered daily during the first 3 weeks. Walking-track analysis and electrophysiological and histological-morphometric studies were carried out 4, 6, 8, 10, and 12 weeks postoperatively (subgroups a, b, c, d, and e, respectively, n = 6 each). Data analysis showed that 1) the recovery of motor function, as measured by walk pattern analysis and evoked muscle action potential, and 2) the orientation, number, myelin thickness, and diameter of myelinated fibers were better in the NGF-7S than in the control group. These findings present strong evidence of the beneficial effect of NGF-7S on peripheral nerve regeneration through inside-out vein grafts.  相似文献   

16.
Over the last decade, several models have investigated the usefulness of different biologic and/or synthetic matrices as alternatives to conventional nerve grafts. Still, axonal regeneration did not occur over longer (> 3 cm) distances. One problem may be that a growth-promoting environment not only includes physical cues but also a rich spectrum of different growth factors only provided by reactive Schwann cells. In the current study, we investigated whether a hybrid graft consisting of first-generation autologous Schwann cells seeded onto an acellular auto- or homograft can aid regeneration across a critical nerve defect in a rat model. In this paradigm, Schwann cells were not expanded in vitro but harvested from the proximal stump neuroma at the time of reconstruction and seeded into either an acellular homo- or autograft. Regeneration was then quantitated with functional muscle testing, regular histology, histomorphometry, and retrograde tracing techniques 12 weeks after reconstruction. Results showed successful regeneration over the entire distance regardless of whether Schwann cells were transplanted onto auto- or homologous acellular matrix. Schwann cells did populate both grafts; however, only sensory axons persisted through the entire distance. The functional outcome was dismal with no motor and poor sensory recovery. Control group C with homologous matrix only without Schwann cells showed no signs of directed axonal regeneration. Control group D with autologous reverse graft showed excellent recovery, as was expected. The present experiment sought to create a hybrid graft where the proximal stump neuroma is used as a biological resource for autologous Schwann cells that are seeded unto an acellular matrix, thus providing both physical and chemical support to regenerating axons. The results are encouraging in that successful regeneration was observed over the entire distance; however, only sensory axons had enough regenerative potential to also make end-organ contact. For motor axons, further refinements in conduit preparation have to be done.  相似文献   

17.
The spinal cord cannot heal after severance because the central nervous system is "non-permissive" to the advancement of axons that regrow from presynaptic motoneurons. With the aim of overcoming paraplegia, the author has carried out extensive experimental research since 1980, first in rats and subsequently in monkeys, severing the cord and connecting its cephalad stump with the muscular nerve branches by means of peripheral-nerve grafts, and using various surgical protocols. Functional connections were established, ascertained by physical, electrophysiologic, and histologic examinations. In this reported study, it is demonstrated that presynaptic motoneurons are also able to reconstruct the cytoskeleton of peripheral neurons, as well as motor end-plates. The possibility of elongation of the axons of presynaptic motoneurons into the peripheral nerve up to the muscle had not previously even been hypotheized. This possibility, which has now been validated, can open the door to new surgical techniques for spinal-cord lesions. In addition, the author presents preliminary results from a single human case, utilizing the surgical procedures of the preceding animal experiments.  相似文献   

18.
Muscle basal lamina: a new graft material for peripheral nerve repair   总被引:13,自引:0,他引:13  
The suitability of muscle basal lamina as a graft material for the repair of peripheral nerves was investigated. Grafts were prepared by evacuating the myoplasm from muscles excised from rats and rabbits. This produced a material consisting mainly of basal lamina and connective tissue, with the basal lamina arranged as parallel tubes. Rat- and rabbit-derived graft material in 0.5-cm lengths was sutured into rat sciatic nerves, and 4-cm lengths of rabbit-derived graft material were interposed into rabbit sciatic nerves. For controls, 0.5-cm nerve autografts were grafted into rats and 4-cm autografts into rabbits. After 2 to 3 months, the success of the grafts was assessed functionally, electrophysiologically, and anatomically. By all these criteria the basal lamina grafts were as successful as nerve autografts; essentially the same number of axons of the same size grew through both graft types, animals recovered their limb function equally well, and the nerve conduction velocities and relative refractory periods were the same in both groups of animals. In rats, following both basal lamina and nerve autografts, the number of axons distal to the grafts was approximately the same as that proximal to them, but axon diameter and speed of conduction were significantly less than normal. The authors conclude that muscle basal lamina grafts are as effective as nerve autografts for repairing severed rat or rabbit peripheral nerves, and suggest that grafts prepared in this way may prove to be useful for nerve repair in humans.  相似文献   

19.
After peripheral nerve injury, minimizing axonal misdirection has been a matter of importance to obtain good functional outcomes. In general, it becomes more challenging as the nerve defect length is longer. As previous works suggested that a conduit repair leaving a short gap could induce some target-specific reinnervation, we expected that a distally placed conduit combined with nerve graft would enhance the specificity of reinnervation, especially in dealing with a long gap. To test this, a 14-mm-long gap was created in the rat sciatic nerves and repaired with either 1) whole nerve graft (WG), 2) interfascicular nerve grafts (FG), or 3) whole nerve graft combined with distally placed silicone tube leaving a 5-mm gap (TUBG). At the end of follow up, the extent of target specific reinnervation (measurement of the compound muscle action potentials evoked by stimulation of the sciatic nerve and its tibial and common peroneal fascicles) and the accuracy of motoneuronal projection (sequential retrograde labeling of the common peroneal motor pool) were assessed. Both assessments revealed that groups FG and TUBG had a similar selectivity, which was significantly higher than in group WG. Consistent with these results, the functional recovery as assessed by walking track analysis showed no significant difference between groups FG and TUBG, whereas those were significantly superior to group WG. In contrast, histomorphometric assessment of the regenerating axons and wet muscle weight showed no significant difference among the three groups. In conclusion, conduit repair would have some effects on reducing motor axonal misdirection, and it might be more effective when used in the management of a large defect in combination with nerve graft.  相似文献   

20.
About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.  相似文献   

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