Long-term evaluation of rat peripheral nerve repair with end-to-side neurorrhaphy

This study was designed to assess long-term reinnervation of end-to-side neurorrhaphy in the rat. The cut right peroneal nerve was repaired and sutured to the side of the intact tibial nerve. Both the extent of reinnervation and the integrity of the intact donor nerve were evaluated in 48 Sprague-Dawley rats randomly treated with fresh or delayed nerve repair with or without perineurotomy. Evaluations included nerve conduction velocity (NCV) of both the peroneal and tibial nerves, dry muscle weight, and histologic examination (neurofilament stain and morphometric assessment) at 8 and 12 months postoperatively. Although animals treated with perineurotomy tended to have better NCV and dry muscle weight recovery than those without, the difference was not statistically significant. No difference was observed between fresh and predegenerated nerve repair. The mean total (all four subgroups) NCV recovery rates were 87 percent and 94 percent for the peroneal nerve, and 93 percent and 95 percent for the tibial nerve, compared to the contralateral intact nerves, at 8 and 12 months, respectively. Tibialis anterior muscle mass measurements revealed a recovery in dry muscle weight of about 85 percent and 89 percent at 8 and 12 months, respectively, compared to the intact contralateral tibialis anterior muscles. Histologic studies with neurofilament staining revealed numerous axons at the distal end of the peroneal nerve in all groups, indicative of myelinated axonal regeneration. Morphometric analysis demonstrated that the presence of a window in the perioneurium improved the histologic picture. The mean number of myelinated fibers at 12 months postoperatively was significantly higher in animals with a perineurotomy window (compared to without) in both fresh and predegenerated nerve repair subgroups, respectively (p <0.05). These results indicated that end-to-side neurorrhaphy permits axonal regeneration from the intact donor nerve and is associated with satisfactory recovery. The effect of the procedure on the donor nerve was negligible.     

Reinnervation after end-to-side nerve coaptation in a rat model

We assessed the effectiveness of end-to-side nerve coaptation by evaluating the extent of reinnervation and the integrity of the donor nerve in the rat. Fifty-six Sprague-Dawley rats were randomly divided into "fresh" and "predegenerated" (delayed) repair groups with or without a window in the perineurium. The right peroneal nerve was cut and sutured to the tibial nerve in an end-to-side fashion. Two and 3 months postoperatively, we measured the nerve conduction velocity (NCV) of the peroneal and tibial nerves, took dry muscle weights, and performed histologic studies. Peroneal NCV recovered up to 71% (2 mo) and 79% (3 mo), and tibial NCV recovered up to 88% (2 mo) and 91% (3 mo). The latter results indicate that this procedure had a slightly negative effect on donor tibial NCV. Dry weight of the tibialis anterior muscle returned to 60% (2 mo) and 82% (3 mo) of that of the contralateral side. Histologic results showed that there were numerous regenerating axons in the distal end of the peroneal nerve. Presence of a window in the perineurium improved the histologic profile significantly.     

Low-power laser biostimulation enhances nerve repair after end-to-side neurorrhaphy: a double-blind randomized study in the rat median nerve model

Previous studies have shown that low-power laser biostimulation (lasertherapy) promotes posttraumatic nerve regeneration. The objective of the present study was to investigate the effects of postoperative lasertherapy on nerve regeneration after end-to-side neurorrhaphy, an innovative technique for peripheral nerve repair. After complete transection, the left median nerve was repaired by end-to-side neurorrhaphy on the ulnar donor nerve. The animals were then divided into four groups: one placebo group, and three laser-treated groups that received lasertherapy three times a week for 3 weeks starting from postoperative day 1. Three different types of laser emission were used: continuous (808 nm), pulsed (905 nm), and a combination of the two. Functional testing was carried out every 2 weeks after surgery by means of the grasping test. At the time of withdrawal 16 weeks postoperatively, muscle mass recovery was assessed by weighing the muscles innervated by the median nerve. Finally, the repaired nerves were withdrawn, embedded in resin and analyzed by light and electron microscopy. Results showed that laser biostimulation induces: (1) a statistically significant faster recovery of the lesioned function; (2) a statistically significant faster recovery of muscle mass; (3) a statistically significant faster myelination of the regenerated nerve fibers. From comparison of the three different types of laser emissions, it turned out that the best functional outcome was obtained by means of pulsed-continuous-combined laser biostimulation. Taken together, the results of the present study confirm previous experimental data on the effectiveness of lasertherapy for the promotion of peripheral nerve regeneration and suggest that early postoperative lasertherapy should be considered as a very promising physiotherapeutic tool for rehabilitation after end-to-side neurorrhaphy.     

Neurohistochemical analysis of regeneration in rat peripheral nerve after end-to-side neurorrhaphy

We investigated the regenerative capacity of motor nerves repaired by end-to-side or end-to-end neurorrhaphy, using choline-acetyltransferase (ChAT) activity measurement or histological analysis. The right medial gastrocnemius nerves (MGNs) of 62 male Fisher strain rats were transected and divided into three groups. In group 1, the distal ends of the MGN were coapted to the side of the lateral gastrocnemius nerve, using a Y-shaped silicone tube in end-to-side neurorrhaphy. In group 2, the nerve ends were reconnected by the traditional end-to-end technique. In group 3, the nerve ends were separated and remained unrepaired. The MGNs were sampled 1, 2, and 3 months postoperatively for histological examinations and ChAT activity measurement. The medial gastrocnemius muscle (MGM) was also sampled for histological evaluations. Axonal regeneration of MGN and the recovery of MGM to nearly normal histology and weight were observed in groups 1 and 2 3 months postoperatively. Although there were no significant differences in ChAT values between groups 1 and 2, the values were significantly larger than that of group 3 3 months postoperatively. These findings suggested that end-to-side neurorrhaphy would be an alternative treatment for peripheral nerve injury in certain clinical situations. Received: June 5, 2000 / Accepted: August 25, 2000     

应用端侧吻合修复高位尺神经损伤的研究

目的 探讨高位尺神经损伤后尽早恢复手内在肌功能的一种修复方法。方法 纯种大耳白兔18只，采用同体自身对照方法。左侧高位尺神经切断后直接吻合，同时在低位（前肢远端）切断尺神经，将其远侧断端与正中神经外膜开窗处作端侧吻合为实验侧，右侧尺神经高位切断后直接吻合为对照侧。按手术先后分为A、B、C三个时间组，分别于术后4、8、12周时做电生理检测和组织学检查。结果 A、B、C三组实验侧均测出诱发电位，而对照侧均未测出诱发电位。组织学观察结果显示术后4、8、12周时实验侧神经纤维数量、密度随时间延长而逐渐增加．而对照侧未检测到再生神经纤维。结论 高位尺神经损伤后在高位端端吻合恢复手外在肌功能的同时加低位端侧吻合可作为尽早恢复手内在肌的功能的一种新方法。     

神经端侧吻合的实验研究

目的：研究神经多个端侧吻合后远端神经的再生情况,并与一干单一神经端侧吻合进行比较,探讨其可行性及临床应用价值。方法：选用Wistar雄性大鼠36只,随机分成A、B组。A组：于右侧锁骨下将肌皮神经、尺神经、桡神经切断,并在正中神经干侧方的外膜上分别开3个1mm“小窗”。将离断神经的远端依次端侧吻合到正中神经的“开窗”处,B组：于右侧锁骨下将尺神经切断,远端端侧吻合到正中神经侧方的“开窗”处,两组左侧均不予处置,为对照侧,术后行神经电生、组织学、电镜及神经纤维计数等检查。结果：神经端侧吻合后,肌皮神经、尺神经、尺神经、桡神经远端均有不同数量的有髓神经纤维再生,且A、B组的尺神经远端神经再生数量的差异显著性。两组的正中神经主干功能的未受到明显影响。结论鼠类动物神经端侧吻合后,远端神经可再生。     

IGF-I and end-to-side nerve repair: a dose-response study

End-to-side nerve repair allows for target-muscle reinnervation, with simultaneous preservation of donor-nerve function. Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerve. The purpose of the current project was to determine the effects of IGF-I in a rat model of end-to-side nerve repair. The left musculocutaneous nerve of 18 adult male Sprague-Dawley rats was fully transected to induce biceps-muscle paralysis. The distal stump of the musculocutaneous nerve was then coapted by end-to-side neurorrhaphy through a perineurial window to the ipsilateral median nerve. All animals were randomly assigned to three groups: Group A received 100 microg/ml IGF-I; Group B received 50 microg/ml IGF-I; and control Group C received 10 mM acetic acid vehicle solution. Infusions were regulated by the Alzet model 2004 mini-osmotic pump, with an attached catheter directed at the coaptation site. Weekly postoperative behavioral evaluations revealed significantly increased functional return over control in both experimental groups as early as 3 weeks. After 28 days, histology evaluations revealed statistically significantly higher musculocutaneous nerve axon counts and myelin thickness/axon diameter ratios in both experimental groups vs. controls. The three groups were not significantly different in motor endplate counts of the biceps muscle. Groups A and B were not significantly different in all parameters tested. This study suggests that local infusion of IGF-I may expedite the functional recovery of a paralyzed muscle, by increasing the rate of axon regeneration through an end-to-side nerve graft.     

Recovery of touch after median nerve lesion and subsequent repair

Many techniques have been developed for the evaluation of peripheral nerve function. Consequently, physicians use different techniques in the clinic. This study describes the evaluation of touch after median nerve lesions in the forearm and repair. In order to evaluate touch, 25 patients, aged 11-51 years (mean, 29 years), were evaluated 3-10.5 years (mean, 5 years) after median nerve repair. The evaluation included the moving two-point discrimination test and Semmes-Weinstein monofilaments. We showed that 32% good-excellent results can be obtained with difficult nerve lesions. The results could have been improved if a sensory reeducation regime had been applied.     

Axonal supercharging technique using reverse end-to-side neurorrhaphy in peripheral nerve repair: an experimental study in the rat model

OBJECT: In an attempt to improve peripheral nerve repair, the influence of the addition of reverse end-to-side neurorrhaphy for an injured peripheral nerve was investigated in the rat sciatic nerve transection model. METHODS: Twelve Sprague-Dawley rats were divided into two groups (six rats in each group). In Group I, the right sciatic nerve was cut at a point distal to the gluteal notch and repaired using end-to-end neurorrhaphy with four 10-0 nylon epineurial sutures. In Group II, after performing the same procedure as in Group I, the left sciatic nerve was cut distally and passed through a subcutaneous tunnel to the right side. The proximal stump of the left sciatic nerve was coapted to the epineurial window of the right sciatic nerve distal to the injured point in an end-to-side fashion using 10-0 nylon epineurial sutures. The effects were evaluated using analgesimeter recordings for the hind paw, electrophysiological tests, measurement of the muscle contraction force, a double-labeling technique, weight measurement and histological examination of the gastrocnemius muscle, histological examination of the bilateral sciatic nerves, and immunofluorescent staining. RESULTS: Results from the many tests used to evaluate the reverse end-to-side neurorrhaphy technique indicated that functional recovery of the denervated target organs was promoted by axonal augmentation. CONCLUSIONS: The reverse end-to-side neurorrhaphy technique could be useful in peripheral nerve repair.     

Long-term evaluation of rabbit peripheral nerve repair with end-to-side neurorrhaphy in rabbits

This study was designed to quantitatively assess long-term end-to-side neurorrhaphy in rabbits. The cut right ulnar nerve was repaired and sutured to the median nerve, in which a perineurial window was created in an end-to-side fashion 3 cm above the elbow joint. Both the extent of the reinnervation and the integrity of the intact donor nerve were evaluated in 36 rabbits randomly treated with fresh or delayed nerve repair. Evaluations included motor nerve conduction velocity (MNCV), dry muscle weight (DMW), and histological examinations at 9 and 12 months postoperatively. The recovery rates of MNCV were 90.1% and 92.8% for the ulnar nerve, and 95.7% and 96.8% for the median nerve, compared to intact contralateral nerves at 9 and 12 months, respectively. MNCV was not detectable for the ulnar nerve in control animals, while it was normal for the median nerve. Recoveries of flexor carpi ulnaris dry muscle weight of about 90.7% and 94.5% were observed at 9 and 12 months postoperatively, respectively. However, muscle mass measurements revealed a recovery of only 31.3% and 27% for control groups at 9 and 12 months postoperatively. The differences between experimental groups and control groups were statistically significant (P < 0.01). Neurofilament and silver stains showed numerous sprouting axons originating from the median nerve to the ulnar nerve. The results indicate that end-to-side neurorrhaphy could induce axonal sprouting from the main nerve trunk of upper limbs in rabbits, leading to useful functional recovery.     

端侧神经吻合后再生状况的实验研究

目的研究端侧神经吻合后,神经再生的可能性和再生纤维的类型.方法将失神经后的兔耳大神经制成端侧吻合模型,12只动物被分成2、4、6、8和12周5个实验组和1个正常对照组,在受神经侧注入HRP逆行示踪,实验到期后对耳大神经纤维和相应的神经节进行HRP染色和CGRP的免疫组化染色,光镜下观察结果.结果逆行示踪显示,神经端侧吻合2～4周时,供神经侧C2、C3背根神经节内无HRP标记阳性的细胞,至第6周,背根神经节内开始出现HRP阳性细胞,8～12周阳性细胞的数量更多,尤其是胞体直径在50μm以上的阳性细胞数显著增加;2～4周时CGRP免疫组化的染色显示,背根神经节内的CGRP阳性标记细胞逐步增强,6周以后阳性标记的细胞数量增加,阳性细胞的胞体直径在12～40 μm范围内,属于中小直径的细胞胞体,同时观察到供神经纤维内的CGRP阳性纤维逐步增多,并跨越神经吻合口长入受神经体内,8～12周背根神经节内的CGRP阳性标记细胞的增加不显著,吻合口及受神经体内的神经纤维也增加不明显.结论端侧神经吻合后再生纤维可长入移植体,纤维再生的顺序是细小类的纤维首先再生.     

Detection of E-cadherin expression after nerve repair in a rat sciatic nerve model

After four nasal aesthetic functional surgeries in a period of 18 months, a 46-year-old woman was evaluated who presented with moderate functional alteration, saddle-nose deformity, and total loss of the septal cartilage. Four months before presentation the patient sustained severe nasal trauma, resulting in depression of the nasal bridge without loss of function. Her problem was diagnosed initially as a consequence of an infected septal hematoma and loss of the septal cartilage. Based on this diagnosis, the patient was subjected, in an 18-month period, to four reconstructive surgeries by different specialists, without any improvement and with worsening of clinical presentation. During the authors' physical examination of the patient, she demonstrated marked nasal cutaneous retraction, atrophic nasal conchae with total loss of the septal cartilage, and a large loss of septal bone. Three nasal mucosa biopsies were acquired and the authors proceeded to carry out complete nasal reconstruction using external cranial table and rib cartilage. Histopathologically, a lesion was noted that was compatible with angiocentric lymphoma, for which treatment was administered according to this type of illness. The authors point out the importance of establishing an adequate diagnosis in the face of an apparently obvious clinical case, present cross-disciplinary treatment, and discuss the study protocol that should be used for this type of pathology. They present their reconstructive technique of the nasal structure using a combination of bone tissue and cartilage, the results, and the current state of the patient.     

外源性神经生长因子对外周神经侧枝发芽GAP-43表达的调控

目的：通过对神经侧支发芽过程中外源性神经生长因子对生长相关蛋白-43（gr owt h associ at ed pr ot ei n-43,GAP-43）的调控,探讨神经侧支发芽再生的机制。方法：SD大鼠共40只,建立胫腓神经端侧吻合模型,随机分为神经生长因子（nervegr owt h f act or,NGF）组和生理盐水（SAL）组,各组又分为1周、2周、4周和8周组。切取吻合近端和远端神经纵切片标本,进行GAP-43的免疫组织化学反应,并结合计算机图像分析进行反应强度的半定量分析。结果：NGF组GAP-43表达显著增高。结论：应用NGF可以促进端侧吻合后神经侧支发芽。     

Recovery after delayed nerve repair: influence of a pharmacologic adjunct in a primate model.

Inhibition of calpains in skeletal muscle by the tripeptide, leupeptin, after median-nerve transection in the mid-forearm and a delayed nerve repair of 3-weeks duration, was studied in a primate (Cebus apella) model. Results indicated that leupeptin facilitates axon regrowth and neuromuscular recovery after delayed nerve repair. Toxicologic testing showed that leupeptin, administered at 18 mg/kg intramuscularly, twice daily for 24 weeks after delayed nerve repair, did not adversely affect hematology, clotting, blood chemistry, or echocardiogram profiles. These data indicate that leupeptin is an effective and safe adjunct to delayed nerve repair.     

Functional assessment of misdirected axon growth after nerve repair in the rat

Age, late repair, loss of nerve tissue, tension, and other factors are now known to influence axon regeneration and the quality of recovery after nerve repair. Many of the factors cannot be controlled by surgery. However, a few important ones depend on surgical technique, and some could be minimized, e.g., suture with tension, scarring due to foreign material, and misdirected axon growth. In this study, the authors tried to assess the functional consequences of misdirected axon growth in the sciatic nerve of the rat. They used a strainless coaptation nerve-repair technique with bioabsorbable plate support (polylactic acid), permitting them to study only the consequences of misdirected axon growth, without tension or suture in the area of nerve repair. Sixty rats were divided into three groups. In Group 1, 20 sciatic nerves were repaired without rotation of the distal nerve stump. In Group 2, 20 sciatic nerves were repaired with a 90-degree rotation of the distal nerve stump. In Group 3, 20 sciatic nerves were repaired with a 180-degree rotation of the distal nerve stump. Functional analyses were performed with the sciatic functional index. The results showed the poor consequences of incorrect nerve-end alignment in nerve repair (p < 0.05). Nerve repair with bioabsorbable plate support is known to allow good stump coaptation, without tension and without foreign material. The authors suggest an adaptation or modification of this technique, which might minimize misdirected axon growth, one of the factors whose effects can be mitigated by surgical technique.