Collagen nerve protector in rat sciatic nerve repair: A morphometric and histological analysis

Peripheral nerve repair is often complicated by fibroblastic scar formation, nerve dysfunction, and traumatic neuroma formation. Use of bio‐absorbable protective wraps may improve outcomes of these repairs. This study histologically compared the incidence of neuroma formation, connective tissue proliferation, and axonal regrowth in transected rat sciatic nerves repaired with and without tubular collagen nerve sleeves. Twenty Sprague‐Dawley rats underwent unilateral sharp sciatic nerve transection and microscopic nerve repair with four epineural sutures and were randomly treated with or without an encircling collagen nerve sleeve. Normal nerves from the contralateral sciatic nerve were also examined. At sacrifice three months later, the nerves were evaluated for traumatic neuroma formation, perineural scar formation, and morphometric analysis. Histological examination of normal and repaired nerves by a neuropathologist demonstrated healing, minimal Wallerian degeneration and no traumatic neuroma formation. Distal section analysis (nine nonwrapped, 10 wrapped), revealed no significant differences in total fascicular area, myelinated fibers per nerve, fiber density, myelin area per nerve, myelinated fiber diameter, axon diameter, myelin thickness, or G‐ratio. Significantly greater (P = 0.005) inner epineural connective tissue formation was observed in nonwrapped nerves (0.62 mm² ± 0.2) versus wrapped nerves (0.35 mm² ± 0.16). The ratio of connective tissue to fascicular area was larger in nonwrapped (1.08 ± 0.26) versus wrapped nerves (0.63 ± 0.22) (P < 0.001). This study demonstrated decreased inner epineural connective tissue formation with use of a collagen nerve wrap during primary repair of peripheral nerve transection in a rat sciatic nerve model. © 2010 Wiley‐Liss, Inc. Microsurgery 30:392–396, 2010.     

Conventional versus epineural sleeve neurorrhaphy technique: functional and histomorphometric analysis

Three methods of nerve repair involving the epineural sleeve technique were compared with conventional nerve repair using the rat sciatic nerve transection model in four groups. In group 1, the sciatic nerve was repaired using the conventional epineural technique by placing four sutures. In groups 2, 3, and 4, the epineural sleeve technique was combined with two sutures, fibrin glue, and two sutures with fibrin glue, respectively. Functional recovery was evaluated using walking track analysis, limb circumference, and the severity of toe contracture. Diameter of the sciatic nerve fibers, total number of myelinated fibers, diameter of the myelin sheath, and the axon-to-fiber diameter ratio were measured at 12 weeks. The results showed better functional recovery as well as a higher number of myelinated fibers in groups using the epineural sleeve technique compared with conventional technique ( < 0.05). The addition of fibrin glue, however, did not make any significant difference. The epineural sleeve technique was found to be superior when compared with conventional nerve repair, providing faster functional recovery and improved nerve regeneration.     

Turnover epineural sheath tube in primary repair of peripheral nerves

The epineural repair technique, which is the gold standard of peripheral nerve injuries, is still far from being ideal. The purpose of this study was to investigate the effects of the turnover epineural sheath tube (TEST) when used over the primary nerve repair site to improve nerve regeneration. Twenty-five Wistar rats were divided into three groups and were operated. In the sham control group, the sciatic nerve was dissected from the sciatic notch to its bifurcation and was left intact. In the primary epineural repair group an incision was made on the nerve and it was repaired using six epineural sutures. In the TEST group, after the incision was made the nerve ends were approximated with two epineural sutures. A proximal circular epineural incision was then made to enable the epineurium to be turned and slid over the repair site. Functional recovery was evaluated by walking tract analysis, and the sciatic functional index was calculated. Histomorphometric studies of the sciatic nerves and gastrocnemius muscles were also performed 3 months postoperatively. Three months postoperatively, functional analysis and nerve and muscle histomorphometric studies revealed similar results in the primary repair and TEST groups. There was no significant difference (p > 0.05) between the results of the TEST and the primary nerve repair groups. However, during the microscopic examination, a decrease in both foreign material reaction and an inflammatory response with less fibrosis were observed in the TEST group. The TEST has a nerve-healing property similar to primary epineural repair, with the advantage of a reduced number of sutures, which decreases the fibrosis around the repair site. The TEST is an alternative treatment modality among other techniques, especially for polyfascicular peripheral nerves.     

Epineural sleeve neurorrhaphy: surgical technique and functional results--a preliminary report

This study was conducted to evaluate the effect of epineural sleeve neurorrhaphy on peripheral nerve regeneration. A total of 12 Lewis rats were divided in two groups of 6 rats each. In group 1, the rat sciatic nerve was transected and repaired using the conventional epineural technique with four sutures. In group 2, the epineural sleeve technique was introduced with two sutures only. Functional recovery was evaluated at 1, 2, 4, 8, and 12 weeks by walking track analysis (sciatic function index [SFI]), mean limb circumference ratio, and severity of toe contracture. Although the SFI at 12 weeks revealed no difference between the two groups (+/-88.39 +/- 10.75 conventional group, +/-77.35 +/- 17.06 epineural sleeve group), significant differences in SFIs were detected at 4 and 8 weeks, with better functional recovery in group 2 rats (4 weeks: 125.92 +/- 22.73 conventional group, +/-99.17 +/- 5.45 epineural sleeve group; 8 weeks: +/-96.65 +/- 4.73 conventional group, +/-72.82 +/- 17.11 epineural group; p < 0.05 for both time points). Mean limb circumference ratio was not significant at all time points. At 12 weeks, all animals in the conventional nerve repair group developed severe toe contractures whereas only 2 animals in epineural sleeve repair group had contracture (p < 0.05). In this study, the epineural sleeve technique demonstrated a faster functional recovery when compared with the conventional technique, as confirmed by SFI and toe contracture grading.     

Diverse types of epineural conduits for bridging short nerve defects. An experimental study in the rabbit

In this study the process of peripheral nerve regeneration through an epineural flap conduit was examined using four groups of 126 New Zealand rabbits. There were three study groups (A, B, and C) and 1 control group (D). A 10-mm long sciatic nerve defect was bridged either with 3 variations of an epineural flap (Groups A, B, and C) or with a nerve autograft (Group D). Animals from all groups were examined 21, 42, and 91 days postoperatively to evaluate nerve regeneration employing light microscopy and immunocytochemistry. Nerve regeneration was studied in transverse sections at 3, 6, and 9 mm from the proximal stump. The gastrocnemius muscle contractility was also examined prior to euthanasia at 91 days postsurgery in all groups using electromyography. Immunohistochemical, histochemical and functional evaluation showed the presence of nerve regeneration resembling the control group D, especially in group A, where an advancement epineural flap was used. In this experimental model an epineural flap can be used to bridge a nerve defect successfully.     

Effects of tension at the site of coaptation on recovery of sciatic nerve function after neurorrhaphy: evaluation by walking-track measurement, electrophysiology, histomorphometry, and electron probe X-ray microanalysis.

The effects of tension at the site of coaptation on recovery of sciatic nerve function after neurorrhaphy were studied by evaluating walking-track measurements, nerve conduction velocity measurements, histomorphometry, and electron probe X-ray microanalysis. Forty adult male Lewis rats underwent right sciatic nerve (SN) transection followed by one of four different nerve repair procedures (N = 10 rats per group). In Group 1, the gap was repaired by end-to-end epineural coaptation. In Group 2, a 5-mm segment of SN was resected, and the defect was repaired under high tension by epineural neurorrhaphy. In Group 3, a 5-mm segment of SN was resected, and the defect was repaired with a 5-mm interposition nerve graft. In Group 4, a 5-mm segment of SN was resected. Then, to lessen the tension that follows neurorrhaphy, an anchoring suture was added. Finally, end-to-end coaptation was performed. Walking-track analysis showed better functional recovery in Group 1 than in Group 2, and better recovery in Group 3 than in Group 2. Group 4 showed a tendency toward better recovery comparing with Group 2. Electron probe X-ray microanalysis revealed higher Na, Cl, and K peaks in axoplasm accompanied by increase in the endoneural fluid pressure (EFP) in Group 2 than those of Group 1. This higher level of Na, Cl and K may be due to impairment of axonal sodium and potassium transport mechanism in Group 2. Increase in EFP may affect nerve regeneration.     

Effect of platelet-rich plasma on peripheral nerve regeneration

Activated platelets release various growth factors, some of which are recognized to improve nerve regeneration. This study evaluated the effect of platelet-rich plasma (PRP) in end-to-end neurorrhaphy. A total of 45 Wistar rats were used, with the initial five used for PRP preparation. The right hind limbs were used as experimental, with the left as control. The animals were treated in five groups. Group A (n = 4): The right sciatic nerve was dissected only from the sciatic notch to the bifurcation. In all other groups, the nerve was sharply transected and repaired with: group B (n = 8): two sutures; group C (n = 8): six sutures; group D (n = 10): two sutures and PRP; and group E (n = 10): six sutures and PRP. Groups D and E were compared with groups B and C, respectively. Group E had a shorter latency time in electromyography ( P < 0.01) and a thicker myelin layer in the histological evaluation ( P < 0.003) in comparison with group C. These positive effects of PRP were not detected in the nerves were repaired with two sutures. In this animal model, the application of PRP to the repair site helped to improve remyelinization of the sciatic nerve in rats when the epineural repair was done with six sutures.     

Repair of peripheral nerve defects with epineural sheath grafts

In this study, we investigated the potential of using a detubulized flat epineural sheath for bridging nerve gaps as an alternative to nerve autografting. Nerve gaps were created by removing a 1.2-cm segment of sciatic nerves. Later, the epineurium was incised longitudinally, and after fascicle removal, a flat rectangular epineural sheath was created. Five experimental groups (6 rats each) included: autograft and no treatment controls and epineural sheath groups repaired with 1 strip, 2-strip, and full epineural sheath grafts. Assessments performed at 3, 6, and 12 weeks included functional (pinprick, toe-spread), neurosensory (somatosensory-evoked potentials), and histomorphometric evaluations. The functional results of toe-spread, somatosensory-evoked potentials, and histomorphometric data revealed comparable outcomes between autograft, 2-strip, and full sheath grafts, indicating adequate nerve regeneration. Thus, the new epineural sheath graft technique introduced in this study can be considered as an alternative method to standard nerve autografting technique.     

Reliability of sciatic function index in assessing nerve regeneration across a 1 cm gap

To evaluate the validity of sciatic function index as a reliable functional parameter in assessing regeneration of rat sciatic nerve through a 1 cm gap, we undertook the following investigation. Sixty-three adult male Sprague-Dawley rats were assigned to four groups for repair of a 1 cm gap created in the right rat sciatic nerve; 19 rats were repaired with amniotic collagen conduits, 20 with nerve autograft, and 17 with silicone tubes. In seven rats, the gap was not repaired and served as a control. Functional recovery was assessed by de-Medinaceli SFI and by clinical observations, compared with quantitative and qualitative histological results at 4, 10, and 17 weeks postoperatively. The SFI results did not correlate with the histological findings and clinical observations over the observation period in all groups.     

Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats

OBJECT: Peripheral nerve repair surgery is still replete with challenges. Despite technical improvements in microsurgery, classic methods of nerve repair have failed to provide satisfactory results. The purpose of this study was to investigate the effects of amniotic fluid from humans on peripheral nerve scarring and regeneration in rats. METHODS: Forty adult Sprague-Dawley rats were used in this study. After the right sciatic nerve in each rat was transected and repaired using an epineural suture procedure, the nerves were divided into two groups according to the solution applied around the repair site: experimental group, 0.3 ml human amniotic fluid (HAF); and control group, 0.3 ml saline. Macroscopic and histological evaluations of peripheral nerve scarring were performed 4 weeks postsurgery. Nerves treated with HAF demonstrated a significant reduction in the amount of scar tissue surrounding the repair site (p < 0.05). No evidence of a reaction against HAF was noted. Functional nerve regeneration was measured once every 2 weeks by using a sciatic function index until 12 weeks postsurgery. Functional recovery in nerves treated with amniotic fluid occurred significantly faster than that in nerves treated with saline (p < 0.05). Peripheral nerve regeneration was evaluated histomorphologically at 12 weeks postsurgery. Nerves treated with amniotic fluid showed significant improvement with respect to the indices of fiber maturation (p < 0.05). CONCLUSIONS: Preliminary data show that HAF enhances peripheral nerve regeneration. The preventive effect of HAF on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.     

The reduction of extraneural scarring with buccal mucosa graft wrapping around the sciatic nerve: an experimental study in a rat model

Background: The postoperative development of epineural and extraneural scar tissue adversely affects peripheral nerve surgery outcomes. Although several surgical methods, pharmacological agents, and chemical materials have been used to prevent epineural scar formation in both clinical and experimental models, the results are still unsatisfactory. The purpose of this study was to investigate the efficacy of buccal mucosa graft (BMG) wrapping on epineural scarring in an adult rat model.

Methods: Bilateral sciatic nerves were carefully exposed in 24 adult Sprague-Dawley rats, and a circumferential segment of epineurium (0.5?cm) was excised from both nerves. The epineurectomised left nerve segment was wrapped with a BMG (experimental side), while the right nerve segment did not receive any surgical procedure other than the epineurectomy, and served as the control side. To perform gross and histopathological examinations, 12 randomly selected rats were euthanised at 4 weeks postoperatively, and the remaining rats were euthanised at 8 weeks.

Results: The left sciatic nerve that was wrapped with a BMG following epineurectomy showed significantly less nerve adhesion at 8 weeks (p?=?.018), and less epineural scar tissue at both 4 (p?=?.014) and 8 weeks (p?=?.025). Inflammation of the BMG-wrapped nerves was increased at 4 weeks (p?=?.029), but not at 8 weeks.

Conclusion: BMG wrapping decreases postoperative adhesion and scar tissue formation of epineurectomised healthy nerves, despite the presence of increased inflammation in the early postoperative period.     

异体神经段皮下包埋对坐骨神经再生影响的研究

目的　探讨异体周围神经段皮下包埋对坐骨神经再生的影响。　方法　 Wistar大鼠 30只 ,雄性。 6只为供体 (C组 ) ,余随机分为两组。实验组 (A组 ) 12只 ,于右大腿后侧皮下行异体坐骨神经 (15 mm)包埋 ,2周后取出 ,修整为 10 mm的片段移植于左侧新鲜的坐骨神经缺损处 (10 m m)。对照组 (B组 ) 12只 ,于右腿相应部位皮肤切口直接缝合 ,左侧新鲜坐骨神经 (10 mm)原位吻合。术后 2、4、8和 14周行组织学观察 ,14周作电生理测定和电镜观察。　结果　术后 2周 ,A组炎性反应稍重于 B组 ;至 4周时两组的炎性反应程度相似 ,近端少许胶原纤维增生 ;8周时两组的炎性反应基本停止 ,胶原纤维增生稍明显 ;14周时两组神经外膜构成完整 ,束膜、内膜结构无明显差异。再生大量的有髓神经纤维及少量的无髓神经纤维。髓鞘结构完整。再生轴突数目、面积差异无统计学意义 ,束膜厚度、分布及范围相似。运动神经传导速度、峰值及潜伏期差异无统计学意义 (P>0 .0 5 )。　结论　皮下包埋的异体周围神经段虽有一定的炎性反应 ,但仍具有与自体神经移植相似的神经再生引导作用。     

Assessment of effects of pinealectomy and exogenous melatonin administration on rat sciatic nerve suture repair: an electrophysiological,electron microscopic,and immunohistochemical study

Summary Background. Collagen scar formation at the cut end of a nerve, an important problem in clinical practice for neurosurgeons in peripheral nerve surgery, obstructs sprouting of axons into appropriate distal fascicles, and thereby limits nerve regeneration. Researchers attempt to control collagen accumulation in the formation of neuroma by various physical and chemical methods, but these have yielded only limited functional success. This is the first experimental study investigating the effects of melatonin (MLT) on nerve repair and neuronal regeneration in rat sciatic nerve suture repair.Methods. The hypothesis that exogenous MLT administration may inhibit the formation of neuroma in peripheral nerve surgery was investigated in rat sciatic nerve model. In this study, a total of 80 rats were used for control groups (Groups Ia, Ib, IIa, and IId), MLT group (Group Ic), surgical pinealectomy (Px) groups (Groups IIb and IIc), and group of MLT treatment following Px procedure (Group IIe). All animals underwent a surgical intervention consisting of bilateral sciatic nerve section and primary suture repair. At 8 weeks after repair, the animals were killed following completion of recording of nerve action potentials (NAPs). Then, unilateral sciatic nerve specimens including the suture repair region were carefully removed and the excised segments were processed for electron microscopy examination. Afterwards, contralateral sciatic nerve specimens from two animals from each group were removed and stained for immunohistochemical analysis.Results. Results of morphometric analysis revealed that Px procedure caused an elevation of collagen content of the sciatic nerve and macroscopic neuroma formation, and that there was a statistically significant reduction in collagen content of the same region in pinealectomized animals treated with MLT (p<0.001). Accordingly, electrophysiological findings demonstrated that the stimulus intensities required to excite a NAP response were increased in surgical Px group, but the presence of a reduced threshold response was found in the group treated with MLT following Px procedure (p<0.01). Immunohistochemical staining for Type I collagen and Type III collagen was markedly more intense in the epineurium of animals after Px. Virtually no or only weak staining was observed in animals in control groups and the MLT treatment group. Results of immunohistochemical analysis revealed that surgical Px procedure caused a strong immunoreactivity for Type I collagen and Type III collagen in all connective tissue planes of the nerve, especially in the epineurium, and there was a statistically significant reduction in immunoreactivity of the repair region in animals receiving MLT treatment after Px procedure (p<0.001).Conclusion. This study demonstrates that exogenous MLT administration significantly inhibits collagen accumulation in the formation of neuroma in the suture repair site and thereby improves nerve regeneration. From a clinical standpoint, the positive effect of MLT administration on neuroma formation and nerve regeneration seems a particularly attractive treatment option. Therefore, we believe that nerve repair with addition of MLT may be a worthwhile option in addition to other treatment modalities in case of MLT deficiency, such as aging. However, further experimental and clinical studies using functional analysis warranted to confirm this result in future.     

The epineural sleeve technique for nerve graft reconstruction enhances nerve recovery

The purpose of the study was evaluation of nerve recovery following epineural sleeve technique for graft reconstruction in rat sciatic nerve. This technique provides the epineural sleeve to cover and separate the site of coaptation. Animals were divided into three groups: CNG-conventional nerve grafting, ESN-epineural sleeve from recipient nerve stumps, ESG-epineural sleeve from graft. Nerve regeneration was evaluated by pin-prick, toe-spread test, walking track analysis and somatosensory-evoked potentials (SEP), gastrocnemius index (GI), and histomorphometric evaluation. Most parameters (SFI, SEPs, and GI) showed significantly better nerve recovery for ESN group when compared to conventional CNG group. Also ESG group revealed better result for SFI. Better functional results for ESN and ESG groups were further confirmed by histomorphometric analysis: higher axon density and diameters as well as thicker myelin sheath. Epineural sleeve graft technique may be promising method with potential application for nerve reconstructive procedures. Better functional nerve recovery can be anticipated.     

Functional recovery of transected nerves treated with systemic BDNF and CNTF

The purpose of this study was to investigate the effect of systemic co-injections of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringer's solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:35–41, 1998.     

Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts

Aim of the study: Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. Materials and Methods: Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 μL phosphate buffered saline and the ALLO/SVF group received 100 μL SVF (2.25 ± 0.45 × 10⁷ cells) locally where the grafting was performed. Results: Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Conclusions: Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection.     

Photochemical tissue bonding: a promising technique for peripheral nerve repair

BACKGROUND: Photochemical tissue bonding (PTB) is a novel tissue repair technique that uses visible light and a photosensitizing dye to crosslink proteins on tissue surfaces. This technique has been successfully demonstrated in a number of tissue repair models. An ideal nerve repair technique would be atraumatic and avoid placement of foreign bodies at the repair site. The epineurium is suited to photochemical repair as it is thin, translucent and has a relatively high collagen content. This study was designed to determine if PTB could be successfully applied in a peripheral nerve repair model. MATERIAL AND METHODS: Forty Sprague Dawley rats underwent transection of the sciatic nerve. Animals were then randomized to four treatment groups; epineurial suture repair, epineurial cuff with PTB, epineurial cuff alone, and no repair. Functional recovery was assessed at 10 day intervals using walking track analysis and sciatic function index calculations. At 90 days postoperatively animals were sacrificed and sciatic nerves harvested for histology and histomorphometry. RESULTS: Functional recovery in the suture repair and epineural cuff with PTB groups were not significantly different (-70.6 +/- 17.8 versus -76.9 +/- 10.3, P = 0.64) at 90 days postrepair. Histology showed good axonal regeneration with all repair techniques. Histomorphometric analysis found no significant difference between the repair groups. CONCLUSIONS: This study illustrates that peripheral nerves can be successfully repaired using a photochemical tissue bonding technique with results similar to those achieved with the current gold standard. With further development and refinement PTB may prove a useful tool in peripheral nerve repair.     

犬化学去细胞神经同种异体移植的早期观察

目的：以化学去细胞同种异体神经，移植修复犬粗大神经的长段缺损，观察早期功能恢复及神经再生。方法：去细胞神经移植组和自体神经移植组各3犬，分别桥接坐骨神经5.0cm缺损。术后3个月观察其运动功能及神经再生。结果：实验组和对照组在术后功能恢复；移植段内新生神经纤维、新生血管及许旺细胞；吻合口远端有髓神经纤维等方面非常相似。结论：化学去细胞神经作为同种异体神经移植物，在修复粗大和长段神经缺损时不会被宿主排斥和吸收，其早期功能恢复及神经再生与自体神经移植无明显差别。     

Effects of Insulin-like Growth Factor-1 in Motor Nerve Regeneration After Nerve Transection and Repair vs. Nerve Crushing Injury in the Rat

Summary  Despite highest standards in nerve repair, functional recovery following nerve transection still remains unsatisfactory. Non-specific re-innervation of target organs are regarded as one reason for a poor functional outcome. Insulin-like growth factor-1 (IGF-1) has demonstrated promoting effects on sciatic nerve regeneration after crushing injury. Similarly, IGF-1 has shown a direct inductive effect on motoneuron growth associated protein-43 (GAP-43) which is believed to play a role in axon guidance during development.  Based on this fact we have examined the trophic effects of recombinant human IGF-1 on peripheral motor nerve regeneration following transection and epineural repair in rats median nerve. RhIGF-1 (0.5 mg/kg/rat) was administered subcutaneously to the neck of the repaired side for 14 days postoperation. Accuracy of re-innervation of the flexor carpi radialis muscle motoneuron pool was studied by sequential retrograde double labelling technique. Motor recovery was tested with the grasping test. No significant differences between experimental and control animals in accuracy of re-innervation and in recovery of muscle power could be demonstrated. Non-specific re-innervation of the flexor carpi radialis muscle was found in 23.2% in the experimental group and in 24.2% in the control group. These results demonstrate that systemically applied rhIGF-1 failed to improve functional motor recovery after nerve transection and repair in the rat as it was demonstrated after nerve crushing injury in several studies. Furthermore, systemically applied IGF-1 did not improve accuracy of re-innervation after axotomy and repair in adult rats.     

Specificity of Reinnervation and Motor Recovery after Interposition of an Artificial Barrier Between Transected and Repaired Nerves in Adjacency – An Experimental Study in the Rat

Summary  Non-specific re-innervation of target organs caused by misdirected axonal growth at the repair site is regarded as one reason for a poor functional outcome after peripheral nerve transsection and repair. This study investigates the rate of aberrant re-innervation and its influence on motor recovery in the rat sciatic nerve using artificial sheets as barrier between tibial and peroneal nerves.  The sciatic nerve was transsected and repaired as follows: epineural sutures (A×6), fascicular repair of tibial and peroneal nerves respectively (B×8), and the same as in group B, but separating both nerves using an Integra?-sheet with silicone (C×8), or Integra? without silicone (D×8). As control, solely the tibial nerve was transsected and repaired (E×5).  Final investigations after 4 months revealed that in group C, 50% of the Integra?-silicone sheets were dislocated. No dislocation was found in group D. Muscle contraction force of the gastrocnemius muscle was significantly higher in group E as compared to all other groups. However although not significant, group D showed a consistently higher muscle contraction force than groups A, B, and C. Histology in groups A, B, and C with dislocated sheets demonstrated multiple axons growing from the tibial to the peroneal nerve and vice versa. In groups D and E, no such axonal growth was visible. These findings were confirmed by a significantly higher rate of specific re-innervation of the soleus muscle using sequential retrograde double labelling technique.  Results of this study suggest that an artificial sheet such as Integra? bears the potential of preventing aberrant re-innervation between repaired adjacent nerves resulting in improved motor recovery. Clinically, this technique may be of importance for brachial plexus, sciatic nerve, and facial nerve repair.