Origin of regenerated axons in nerve bypass grafts

It has been shown that end-to-side coaptation and nerve bypass grafting, which are essentially two sequential end-to-side coaptations, induce axonal outgrowth in peripheral nerve injuries. However, it is unknown whether the axons regenerated after end-to-side coaptation originate by collateral sprouting at the suture site or by elongation from the spinal neuronal pool. Also unknown is the extent of functional recovery that can be expected after bypass grafting for the reconstruction of injured peripheral nerves. We conducted a study to evaluate the origin of regenerated axons after end-to-side coaptation and the utility of nerve bypass grafting for peripheral nerve injury. For this purpose, we performed electrophysiological studies using bypass grafting (end-to-side coaptation) and conventional cable grafting (end-to-end coaptation) to treat complete paralysis of the peroneal nerve in rabbit models, and compared the recovery time and extent of functional recovery achieved with the two techniques. We assessed, by electromyography, the time to appearance of reinnervation potentials from the tibialis anterior muscle on the affected side. These times were not significantly different in the two study groups of animals (p = 0.5390). After a 12-week recovery period, electrophysiological findings and histological assessment showed similar recovery in both groups of animals. It is known that collateral sprouting of axons from the nodes of Ranvier proximal to the transected nerve stump occurs in cable grafting, and that axon elongation from the spinal cord requires more time. Our findings in the present study strongly suggest that collateral sprouting across end-to-side sutures is the chief means of axonal outgrowth in nerve bypass grafts, and that functional recovery can be expected in bypass grafting to nearly the same extent as in cable grafting.     

Physiologic and morphologic aspects of nerve regeneration after end-to-end or end-to-side coaptation in a rat model of brachial plexus injury.

The results of repairing a transected rat musculocutaneous nerve by suturing the distal stump, end to side or end to end, to the ipsilateral ulnar nerve were assessed at 3 months by retrograde labeling and morphologic and physiologic analysis. Unlike most other models of end-to-side repair in which the injured recipient and donor reinnervating nerves have overlapping neuron pools in the spinal cord, in this model the neurons of the injured musculocutaneous and the reinnervating ulnar nerves are located in mutually exclusive segments of the spinal cord. Using retrograde labeling we show that the reinnervating fibers are derived solely from the ulnar nerve pool. Both end-to-side and end-to-end coaptation resulted in reinnervation of the distal musculocutaneous nerve and significant functional reinnervation of its dependent biceps brachii muscle. Although end-to-end coaptation resulted in better axon morphology and muscle function, it resulted in total loss of donor nerve function. By contrast, end-to-side coaptation resulted in good recovery with only minimal donor nerve deficit. These results show that significant functional reinnervation of biceps brachii muscle can occur solely on the basis of collateral sprouting of intact axons from the adjacent ulnar nerve.     

Current concepts in end-to-side neurorrhaphy

In peripheral nerve injury, end-to-side neurorrhaphy involves coaptation of the distal stump of a transected nerve to the trunk of an adjacent donor nerve. It has been proposed as an alternative technique when the proximal stump of an injured nerve is unavailable or the nerve gap is too long to be bridged by a nerve graft. Experimental and clinical data suggests that end-to-side neurorrhaphy can provide satisfactory functional recovery for the recipient nerve, without any deterioration of the donor nerve function. The most accepted mechanism of nerve regeneration following end-to-side neurorrhaphy is collateral sprouting. The source of the regenerating axons traveling in the epineurium of the donor nerve is thought to be the proximal Ranvier's nodes at the site of end-to-side neurorrhaphy, however, histologic evidence is still lacking. Partial neurotomy of the donor nerve may enhance regeneration of motor neurons through end-to-side neurorrhaphy and reinnervation of motor targets.     

Motor functional and morphological findings following end-to-side neurorrhaphy in the rat model.

Nerve repair cannot always be achieved by the conventional end-to-end technique. This study evaluated the functional recovery of nerves repaired with end-to-side neurorrhaphy in a rat model. The right peroneal nerves of 80 female rats were transected and divided into four groups. In group A, the nerve ends were separated and remained unrepaired; in group B, the distal peroneal ends were directly sutured to the epineurium of the tibial nerves in end-to-side fashion; in group C, the distal ends were sutured through an epineurial window at the repair site in end-to-side fashion; and in group D, the nerve ends were reconnected by the traditional end-to-end technique. Evaluation included gait analysis by calculation of a peroneal functional index, measurement of contractile function of the extensor digitorum longus muscle, wet weight of the extensor digitorum longus, and histological examination. The findings of this study suggested the following: (a) end-to-side neurorrhaphy allows effective motor functional recovery, demonstrated by earlier improvement of the peroneal functional index, stronger muscle contractile function, greater muscle weight, and higher density of regenerated axons compared with unrepaired nerves; (b) removal of the epineurium of the donor nerve at the nerve coaptation site increases the effectiveness of end-to-side neurorrhaphy, but the epineurium appears to be a partial barrier to axonal regeneration; (c) removal of the epineurium does not affect the structure and function of the donor nerve; and (d) end-to-end repair achieved the best functional recovery among the four groups; therefore, end-to-side repair should be considered as a potential alternative only when no proximal nerve is available.     

Schwann cells can induce collateral sprouting from intact axons: experimental study of end-to-side neurorrhaphy using a Y-chamber model.

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.     

Role of the target in end-to-side neurorrhaphy: reinnervation of a single muscle vs. multiple muscles

The authors examined the effects of end-to-side neurorrhaphy for reinnervation of the musculocutaneous nerve (Group A) which innervates the biceps muscle, compared to reinnervation of the median nerve which innervates multiple muscles in a rat model. Additionally, end-to-end neurorrhaphy to the musculocutaneous nerve using one-third of the median nerve (Group B) was investigated. End-to-end coaptation of the musculocutaneous nerve served as a control (Group C). In a grooming test, the biceps muscle function in Group A animals demonstrated a slower but nearly similar good recovery to Groups B and C. Biceps muscle contraction force investigated after 24 weeks demonstrated no statistically significant differences among all groups. In Groups A and B, no significant impairment of the donor median nerve function was found in a grasping test and the muscle contraction force of the flexor carpi radialis muscle, and histologic evaluation of the musculocutaneous nerve showed multiple regenerated axons distal to the coaptation site. Retrograde double-labeling in Group A animals showed reinnervation of the musculocutaneous nerve by median nerve axons located at the coaptation site. These results validate that end-to-side neurorrhaphy to a nerve innervating a single muscle is more efficient than to a nerve innervating multiple muscles, as demonstrated in an earlier study. The reason for this phenomenon is most likely that all sprouting axons are directed toward one target rather than toward multiple targets, with the latter situation resulting in a smaller number of axons and a variable distribution of axons per target. Since donor nerve sprouting axons were observed at the coaptation site, a relevance of the selected site for end-to-side neurorrhaphy is suggested. Both end-to-side neurorrhaphy and end-to-end neurorrhaphy, using one-third of the median nerve, led to useful functional recovery in this rat model, if an agonistic donor nerve is employed.     

A modified end-to-side method for peripheral nerve repair: large epineurial window helicoid technique versus small epineurial window standard end-to-side technique

This study evaluated 2 end-to-side nerve repair techniques for ability to induce nerve sprouting and muscular recovery. Twenty-four rats underwent identical surgeries. The helicoid method of neurorrhaphy was used on the left (large epineurial window) side and the standard end-to-side (small epineurial window) repair on the right side of each rat to repair the peroneal nerve. The helicoid configuration markedly increases the area from which axons can sprout into the recipient nerve. At 11 months after surgery, axons were counted in donor and recipient nerves, and muscle moist weight of the extensor digitorum longus (EDL) and tetanic force were measured. Muscle volume, tetanic force, and moist weight of EDL muscles were significantly higher on the left side (helicoid) than on the right (end-to-side). Histologic analysis and nerve axon counting of the recipient peroneal nerve showed significantly more regenerative nerves on the left than on the right. There were no significant differences between sites above and below the repair site in the donor tibial nerve in regard to mean number of nerve fibers. Helicoid nerve repair can entice more nerve fiber sprouts from the intact donor nerve, improve muscular recovery, and maintain donor nerve health.     

End-to-side neurorrhaphy: evaluation of axonal response and upregulation of IGF-I and IGF-II in a non-injury model.

This research group has introduced a model of end-to-side neurorrhaphy, in which reinnervation occurs without frank damage to donor axons. The current study used in situ hybridization to test the hypothesis that insulin-like growth factor (IGF-I and IGF-II) mRNA levels increase at the coaptation site and grafted nerve following end-to-side repair, and that this increase is associated with axonal sprouting and growth. One week after end-to-side coaptation, IGF-I mRNA was localized predominantly on the epineurial side of the graft perineurium, while IGF-II was seen mainly on the endoneurial side. IGF-I hybridization was greatest at this time and declined by 2 weeks post-procedure. No changes in IGF mRNA levels occurred in the distal donor nerve. The increase in IGF-I mRNA at 1 week preceded the appearance of myelinated axons. The presence of myelinated axons within the graft 2 weeks after end-to-side coaptation was associated with a decline in IGF-I mRNA. These data are the first to demonstrate increased IGF mRNA levels associated with axonal sprouting and growth following end-to-side neurorrhaphy. Moreover, the findings support those of earlier studies by others implicating IGFs in axonal regeneration. The increase in IGF mRNA during sprouting and axonal growth into an end-to-side coaptation indicates that the local therapeutic augmentation of endogenous IGF levels at the coaptation site may enhance axonal sprouting from a minimally injured donor nerve, and thereby increase the number of axons that reinnervate the graft.     

采用神经纤维梳理技术显示神经端侧缝合后侧支再生的研究

目的探讨一种可直接显示神经端侧缝合后神经纤维侧支再生的方法。方法取5只成年Wistar大鼠，将右侧腓总神经切断，远端与外膜开窗的胫神经作端侧缝合。术后3个月切取缝合部位神经和对侧正常胫神经，福尔马林、锇酸和甘油处理后，于手术显微镜下剥离结缔组织，将神经纤维梳理出，并在光学显微镜下观察其形态。另切取缝合口及其远端的腓总神经作组织学检查。结果神经端侧缝合口分离出的神经纤维，可见在郎飞结附近发出细小侧芽，而正常胫神经则未发现。缝合口纵切片见神经纤维从胫神经进入腓总神经，缝合口远端腓总神经横切片见大量再生纤维。结论采用神经纤维梳理技术可直观地显示神经端侧缝合后神经纤维侧支再生的现象。     

不同吻合面积影响神经端侧吻合法修复效果的实验研究

目的比较神经端侧吻合处不同接触面积对周围神经端侧吻合后神经再生的影响,观察面积因素在神经端侧吻合法中的作用。方法选用50只健康SD大鼠,采用右侧腓总神经损伤修复模型。术中根据手术修复方法不同,分为A、B两组,每组25只。每组将右侧腓总神经在其坐骨神经分支后3mm处局部封闭,利刀切断,吻合于胫神经。A组神经远断端切成45°斜面,腓总神经与胫神经端侧吻合;B组神经远断端切成10°斜面,腓总神经与胫神经行端侧吻合。术后第8周分别对三组大鼠进行组织形态学、腓肠肌湿重检测、肌电图、有髓神经纤维计数和神经示踪法观察。结果B组肌湿重检测、肌电图、有髓神经纤维计数检测指标在8周时与A组比较,各项检测指标均存在明显差异（P〈O．05）。结论增大神经断端接触面积后行神经端侧吻合法修复神经,神经纤维再生良好;增大神经断端接触面积能获得更有效的神经再生;长人远端的神经纤维多少与受端吻合接触面积大小有关。     

End-to-side nerve coaptation: a qualitative and quantitative assessment in the primate.

There are several reasons why end-to-side nerve coaptation has not been widely adopted clinically. Among these are the putative damage inflicted on the donor nerve and the variable quality of the regeneration in the recipient nerve. So far experiments on end-to-side nerve repair have been short term and mostly carried out on rats. This long-term study of end-to-side nerve repair of ulnar to median and median to ulnar nerve was performed using adult nonhuman primates. Eleven nerve repairs were studied at different time points. Eighteen, 22, 33 and 57 months after surgery a qualitative and quantitative analysis of the donor nerve and regenerating nerve revealed variable levels of percentage axonal regeneration compared with matched controls (1.4%-136%). Morphological evidence of donor nerve damage was identified distal to the coaptation site in four of the 11 cases, and in these cases the best axonal regeneration in the corresponding recipient nerves was observed. This donor nerve damage could neither be demonstrated in terms of a decrease in axon counts distal to the coaptation nor as donor target organ denervation. Recipient target organ regeneration like the axonal regeneration varied, with evidence of motor regeneration in eight out of 11 cases and sensory regeneration, as measured by percentage innervation density compared with matched controls, varied from 12.5% to 49%. Results from the present study demonstrate that the end-to-side coaptation technique in the nonhuman primate does not give predictable results. In general the motor recovery appeared better than the sensory and in those cases where donor nerve damage was observed there was better motor and sensory regeneration overall than in the remaining cases.     

End-to-side nerve coaptation: is an additional proximal coaptation useful when available?

The aim of this experimental study was to evaluate the effects of end-to-side coaptation of the proximal end of a severed nerve to the same intact nerve, in addition to traditional end-to-side coaptation of the distal end, with an aim to use the intact nerve as a nerve conduit in a rat model and to compare the functional and histologic results of this modality to those obtained after nerve grafting and traditional end-to-side nerve coaptation. In group A, a peroneal nerve defect measuring 1 cm was created in the left hind limb, and a nerve graft 1 cm long was used to bridge the defect. In group B, only the distal stump of the peroneal nerve was coapted to the intact tibial nerve. In group C, both ends of the peroneal nerve defect were coapted to the intact tibial nerve in an end-to-side fashion 1.5 cm apart from each other, and in group D, the peroneal nerve defect was left unrepaired. Group E was consisted of nonoperated peroneal nerves that were used to obtain normative data. Although significantly higher myelinated axon densities were observed in groups B and C compared with group A and group E, total number of the myelinated axons was significantly higher only in group C. Peroneal functional index assessments demonstrated that nerve recovery in the peroneal nerve was similar in groups A and C, and both were better than those observed in groups B and D. Collectively, these results suggest that end-to-side coaptation of both ends of a severed nerve to an intact nerve, in case of a nerve defect in this length, may serve as an alternative for nerve grafting.     

End-to-side neurorrhaphy: an experimental study in rabbits

The concept of end-to-side nerve repair was recently introduced; however, most authors have reported conflicting results with this technique. This study was conducted to assess the effectiveness of end-to-side nerve repair in both fresh and predegenerated specimens by histological evaluation in an animal study in rabbits. Thirty male rabbits were divided into three groups. In group 1 (n = 14), the peroneal nerve was divided and sutured end-to-side to the tibial nerve via an epineurial window. In group 2 (n = 13), the peroneal nerve was divided and sutured end-to-side to the tibial nerve after a 1-week "predegeneration period." In group 3 (n = 3), which was considered the control group, the peroneal nerve was divided and sutured to the adjacent soft tissues. After 3 months, specimens were harvested for histological evaluation. Nerve fiber count, in normal peroneal nerves, averaged 532/cross section. In groups 1 and 2, average nerve fiber count in implanted peroneal nerves was 6.24 and 7.00/cross section, respectively. No significant statistical difference was observed between fresh and "predegenerated" groups (P = 0.90). These data suggest that collateral sprouting of donor nerves is possible after end-to-side neurorrhaphy through an epineurial window, but the number of nerve fibers in recipient nerves is too low to result in any functional recovery in the target organ.     

周围神经端端或端侧吻合后降钙素基因相关肽和P物质免疫组织化学的对比研究

目的　探讨周围神经端端或端侧吻合后神经递质降钙素基因相关肽 (CGRP)和 P物质 (SP)水平的变化。　方法　选取雌性 Wistar大鼠 2 0只 ,随机分为 5组 ,每组 4只 ;实验组为 4组 ,正常对照组为 1组。实验组 :切断双侧腓总神经。将左侧腓总神经远侧断端吻合至胫神经侧方 ,右侧行腓总神经端端吻合 ,术后 1、2、4和 2 7周于各时间点分别在神经吻合口、腰段脊髓和背根神经节处取材 ,每次 4只进行 CGRP和 SP的免疫组织化学染色。对照组 :不行神经切断及吻合术 ,1周后检测同上。　结果　实验组术后 1周在腰段脊髓后角和背根神经节中 CGRP和 SP的表达均显著减少 ,术后 4、2 7周 ,CGRP和 SP在腰段脊髓后角的表达逐渐恢复至接近正常水平 ,但在背根神经节中的表达却无显著变化。端端、端侧吻合的两侧 CGRP和 SP变化的趋势一致 ,但在腰段脊髓后角的 4个时间点的样本中 ,端端吻合的表达显著高于端侧吻合。对坐骨神经进行乙酰胆碱酯酶 (Ach E)、SP、CGRP和 PGP9.5染色显示神经纤维均可通过端端与端侧神经吻合口。　结论　再生的神经纤维可以通过端侧吻合口 ,端侧吻合中感觉神经的恢复与端端吻合相似 ,但恢复的程度稍差于端端吻合。     

自体雪旺细胞促周围神经端侧吻合轴突侧支发芽的实验研究

目的：研究周围神经损伤行端侧吻合口自体雪旺细胞（Sc)移植对端侧吻合的作用，探讨改善端铁合质量的方法。方法：72只Wistar大鼠随机平均分为3组：A组，左腓神经端端吻合组；B组，左胫腓神经端侧吻合组；C组，左胫腓神经端侧吻合后再生小室内注自体雪旺细胞悬液组。于术后2、4、6个月每组分别取8只大鼠取材、检测，依次行大体观察、神经电生理检测、肌湿重、组织学及电镜观察等。结果：C组与B组各项指标比较：肌力、肌纤维截面积、有髓纤维截面积差异有显著性（P＜0．05）。神经电生理、肌湿重、有髓纤维数目差异有非常显著性（P＜0．01），显示恢复较好，某些指标（神经电生理、肌湿重、肌纤维截面积）在6个月时接近A组（P＞0．05）。结论：自体雪旺细胞移植可以促进周围神经端侧吻合轴突侧支发芽，改善端侧吻合口质量。     

Quantitative characterization of regenerating axons after end-to-side and end-to-end coaptation in a rat brachial plexus model: a retrograde tracer study

The efficacy of end-to-side repair as a method of nerve reconstruction has been questioned, and most studies that characterize the mode of re-innervation are marred by inappropriate experimental design and lack quantitative analysis. This makes characterization of re-innervating neurons confusing and consequently controversy remains as to the extent and source of reinnervating axons. In an experimental brachial plexus rat model, we transected the musculocutaneous nerve, labeled its neuron pool with Fast-Blue and joined the distal stump to the side of the intact ulnar nerve, or to the proximal stump of the divided ulnar nerve, to characterize neurons that reinnervate the recipient nerve. Tetramethyl-rhodamine dextran (TMRD) or fluoro-gold was used to map the reinnervating motor and sensory neurons at 12 weeks post-transection. No neurons originally labeled from musculocutaneous nerve were subsequently labeled with TMRD or fluoro-gold, showing that this original neuron pool does not contribute to re-innervation of the distal musculocutaneous nerve, but that reinnervation occurs solely by ulnar nerve motor and sensory axons. In the end-to-side group, 16.4% of the motor and 7% of the sensory donor ulnar nerve neurons re-innervated the musculocutaneous nerve exclusively, and a further 10% motor and 11.6% sensory innervated the musculocutaneous nerve by collateral sprouting of their axons. This compared to re-innervation by 62.6% of motor and 70.4% of ulnar nerve sensory neurons in the positive control that underwent end-to-end repair. Our results confirm the concept of collateral sprouting and support the use of end-to-side repair.     

Effects of vascular endothelial growth factor on nerve regeneration in acellular nerve grafts

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.     

Functional, electrophysiologic, and morphometric evaluation of nerve regeneration from coaptation on regenerated nerve fibers: experimental study in rabbits

The importance of a sufficient number of nerve fibers at a proximal coaptation site is indisputable for the successful repair of nerves; however, the quality of nerve fibers required at this site has yet to be defined. The present study deals with the question of whether it is necessary to trim nerves back to unaffected neuronal tissue or whether the coaptation on recently regenerated nerve fibers, commonly believed to produce a poor quality of repair can, in fact, produce adequate nerve regeneration. Twenty New Zealand White rabbits received a standardized crush lesion on the peroneal nerves of both hind legs. Four weeks later, the nerves of the left hind legs (n = 20) were transected 10 mm distal to the previous crush lesion and coapted to the freshly regenerated nerve fibers. For comparison, on 10 right hind legs, the nerves were transected at the site of previous crushing (Group A, superimposition) or 10 mm proximal to the site of crushing on unscathed nerve fibers (Group B). Eleven weeks later, the quality of nerve regeneration was assessed by the toe-spreading reflex, electrophysiologic data, muscle weight, and histomorphologic evaluation. In the animals of Group A, the quality of nerve regeneration following coaptation on the regrown axons did not differ in any of the examined parameters from the quality of nerve fibers outgrown from the site of the superimposed lesion. Both lesions led to a completely functional reinnervation. Also in Group B, nerve action potential recording and histologic data on both sides did not reveal a significant difference between the number and maturation of nerve fibers equidistant from the suture site, shortly before muscle entrance. With this coaptation model, it could be demonstrated in the peroneal nerve of rabbits, that coaptation to recently regenerated nerve fibers leads to a significant functional regeneration.     

Phrenic nerve end-to-side neurotization in treating brachial plexus avulsion: an experimental study in rats

The aim of this study was to extend the clinical application of phrenic nerve neurotization in treating brachial plexus avulsion injury, reducing the possible damage on the diaphragm function. Fifty-one male Sprague-Dawley rats and 9 transgenic rats were used in this study. Evaluations including behavioral observation, histology, and electrophysiology study were performed postoperatively. The functional recovery of rats with the end-to-side neurorrhaphy reached 80% of those with end-to-end neurorrhaphy, and the function of diaphragm was preserved. The fluorescence study revealed abundant collateral sprouting of the phrenic nerve axons through the coaptation site in all the experimental groups. The study showed that the end-to-side neurorrhaphy in a helicoid manner and the standard end-to-side neurorrhaphy were effective in the treatment of brachial plexus root avulsion injury with little harm to the function of diaphragm. This will extend the clinical application of phrenic nerve neurotization in treating brachial plexus avulsion injury.     

Re-innervation of the bladder through end-to-side neurorrhaphy of autonomic nerve and somatic nerve in rats

End-to-side neurorrhaphy is widely used in the peripheral nervous system for nerve repair; however, the application of this technique has been limited to somatic nerves. The feasibility of nerve regeneration through end-to-side neurorrhaphy between autonomic and somatic nerves with different characteristics in the peripheral nervous system is still undetermined. In this study, rats were divided into three groups for different treatments (n=10 per group). In the end-to-side neurorrhaphy group, left L6 and S1 were transected in the dura, and the distal stump of L6 ventral root was sutured to the lateral face of L4 ventral root through end-to-side coaptation. In the no repair group, the rats did not undergo neurorrhaphy. In the control group, the left L6 dorsal root and S1 roots were transected, respectively, but the L6 ventral root was kept intact. After 16 weeks, the origin and mechanism of nerve regeneration was evaluated by retrograde double labeling technique as well as histological examination and intravesical pressure measurement. Retrograde double labeling indicated that the reconstructed reflex pathway was successfully established and the primary regeneration mechanism involved axon collateral sprouting. Morphological examination and intravesical pressure measurement indicated prominent nerve regeneration and successful re-innervation of the bladder in the neurorrhaphy group, compared with the "no repair" group (p<0.05). No significant changes were observed in the histology of the donor nerve and the bilateral extensor digitorum longus muscles in the neurorrhaphy group. Nerve regeneration may be achievable for nerve repair through end-to-side neurorrhaphy between autonomic and somatic nerves without apparent impairment of donor somatic nerve.