Rat Sciatic Nerve Regeneration Research Articles

Possibility of using nerve segments dissected from human cadavers for grafting: Preliminary report

An intercostal nerve obtained from a human cadaver 6 h post-mortem was transplanted into the rat sciatic nerve and nerve regeneration was observed 4 and 8 weeks after surgery. Sciatic nerves from deceased rats up to 2 days post-mortem were also transplanted for comparison. Good nerve regeneration was observed through the human cadaver-derived graft to the distal segment at the medial plantal nerve 8 weeks after surgery. The results of the present study indicate the possibility that nerves from human cadavers can be used for nerve grafting in clinical applications.

Efeitos das células tronco adultas de medula óssea e do plasma rico em plaquetas na regeneração e recuperação funcional nervosa em um modelo de defeito agudo em nervo perfiférico em rato

OBJETIVOS: Foram avaliados os efeitos do uso de células tronco da medula óssea (CTM) e do plasma rico em plaquetas (PRP) na regeneração de nervos periféricos, utilizando um modelo estabelecido de regeneração de nervo ciático em ratos. MÉTODOS: Um defeito nervoso de 10 mm foi reconstruído com a utilização de um tubo de silicone preenchido com CTM, PRP ou ambos. O grupo controle recebeu somente o tubo de silicone. Foi realizado ainda um quinto grupo no qual o intervalo foi reconstruído utilizando o segmento ressecado do nervo. A função motora foi testada seis semanas após a cirurgia utilizando teste de marcha. Após o teste motor, os ratos foram anestesiados, o nervo ciático e o tubo foram ressecados e foi realizada microscopia eletrônica de transmissão. RESULTADOS: A análise quantitativa demonstra uma melhora na recuperação funcional no grupo CTM em comparação com os demais grupos. Regeneração nervosa foi demonstrada no grupo CTM por microscopia eletrônica de trasmissão com uma recuperação praticamente completa da anatomia neural. CONCLUSÃO: Nossos resultados sugerem que o uso de CTM associado com a técnica de tubulização promove uma satisfatória recuperação da função motora e regeneração nervosa.

Os efeitos do ultra-som terapêutico nas lesões por esmagamento do nervo ciático de ratos: análise funcional da marcha

Background: The effects of therapeutic ultrasound irradiation on peripheral nerve regeneration are not well known, particularly regarding functional recovery. However, in rats, footprint evaluation is a well-systematized method for measuring the Sciatic Functional Index (SFI), showing close correlation with morphological regeneration of damaged sciatic nerves. Objective: To analyze the influence of therapeutic ultrasound on sciatic nerve regeneration in rats subjected to controlled crushing. Method: 20 Wistar rats (mean body weight: 300 g) were divided into two experimental groups: 1) crushing only (n=10); 2) crushing followed by ultrasound irradiation (n=10). Under general anesthesia, a 5-mm segment of sciatic nerve proximal to its bifurcation in the right thigh was exposed and crushed with constant loading of 15 kg for 10 minutes, using a specially-built device. Low-intensity pulsed ultrasound irradiation (1:5, 0.4 W/cm2, 1 MHz, 2 minutes) was started on the first postoperative day and administered for ten consecutive days. Footprints were obtained weekly (postoperative weeks 13) using a specially-designed walkway, and evaluated using specifically-developed software, according to a previously-tested method, with automatic SFI calculation. Results: The SFI progressively increased in both groups: Group 2, from 101 in the first week to 59.21 (second) and 26.68 (third), i.e. 73% improvement overall; Group 1, from 98.2 (first) to 79.5 (second) and 44 (third), i.e. 55% improvement overall. The differences between the groups were significant for the second and third weeks (p=0.02 and p=0.002, respectively). Conclusion: Low-intensity therapeutic ultrasound accelerates the regeneration of crushed sciatic nerves in rats, as demonstrated by its functional recovery.

Electrical Stimulation on Rat Sciatic Nerve Regeneration

Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery.Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 μmol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery.In the control versus citicoline-treated rats, SFI was −90 ± 1 versus −84 ± 1 (P < .001), −76 ± 4 versus −61 ± 3 (P < .001), and −66 ± 2 versus −46 ± 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16 400 ± 600 number/mm2 and 5.47 ± 0.25 μm versus 22 250 ± 660 number/mm2 (P < .001) and 6.65 ± 0.28 μm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 ± 0.1) significantly better than that in controls (2.6 ± 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001).Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.

Gene Transfer to Dorsal Root Ganglia by Intrathecal Injection: Effects on Regeneration of Peripheral Nerves

Gene delivery to sensory neurons of the dorsal root ganglion (DRG) offers the prospect of developing new clinical interventions against peripheral nerve diseases and disorders. Here we show that genes can be transferred to rat DRG through lumbar intrathecal injection of delivery vectors into the cerebrospinal fluid. Genes could be transferred to DRG using polyethylenimine (PEI)/DNA complexes, Lipofectamine 2000/DNA complexes, adeno-associated virus vectors, or baculovirus vectors. We also show that nerve growth factor cDNA, delivered through lumbar intrathecal injection of PEI complexes, was able to improve regeneration of transected rat sciatic nerves. These data demonstrate the viability of using an intrathecal gene delivery approach for treating peripheral neuropathies.

Suitable dose of nerve growth factor in the poly d, l-lactic acid/nerve growth factor compound conduit

目的 探讨外消旋聚乳酸/神经生长因子(PDLLA/NGF)复合导管中促进大白鼠神经再生的神经生长因子的合适含量.方法 Wistar雌性大白鼠40只,随机分为5组,每组8只.各组采用PDLLA/NGF复合导管中的NGF含量分别为100u、250u、400u、500u和800u.将每组动物的右侧坐骨神经造成10mm缺损的间隙,分别以不同NGF含量的PDLLA/NGF复合导管桥接缺损.术后6个月检测比较各组坐骨神经的再生情况.结果 NGF含量为400u和500u的PDLLA/NGF复合导管桥接组的神经再生情况显著优于其它3组(P＜0.01或P＜0.05),而该2组间的差异无统计学意义(P＞0.05).其余3组中,NGF含量为800u组的神经再生情况最差.结论 PDLLA/NGF复合导管中NGF的含量为400～500 u左右,对促进大白鼠神经再生最为合适.NGF含量过高反而不利于神经再生。

Effect of FK506 on axonal regeneration of rat sciatic nerve in regeneration chamber: an experimental study

To evaluate the effect of FK506 on expediting nerve regeneration of rat Sciatic Nerve in regeneration chamber and to look for a proper way of its administration to treat peripheral nerve injuries. Sixty adult male SD rats which were randamizely divided into 3 groups received a neurotomy to bilateral sciatic nerves, then we reconnected the broken nerves with silicon tube to make regeneration chambers. The regeneration chambers were filled with either normal saline (group A and group B) or 1 microg/ml FK506 (group C). The rats of group B also received daily injection of FK506 (1 mg/kg) at the back of the neck for 14 days. Local immunoreaction, weight of fresh gastrocnemius muscles, histological changes and electrophysiology were observed at designate time after neurotomy. At 6 weeks postoperation the extent of local lymphocytes infiltration in group B and C were less than that in group A, all results in group B were much better than that of group A. Results of group C were better than that of group A without significance. (1) Systemic administration of FK506 (1 mg/kg) showed neuroprotective and neurotrophic effect, which can facilitate nerve regeneration and promote functional recovery. (2) Local administration of FK506 (1 microg/ml) showed some extent of neuroprotective effect at early period of nerve injury, but the neurotrophic function is uncertain and still needs to be studied further.

Effect of pulsed magnetic field on regenerating rat sciatic nerve: An in-vitro electrophysiologic study

Some experimental studies report that low-frequency pulsed electromagnetic field (PEMF) stimulation may accelerate regeneration in peripheral nerves. In the present study, effects of PEMF on the regeneration of the crushed rat sciatic nerves were investigated with histological and in-vitro electrophysiological methods (sucrose-gap). After crush injury of the sciatic nerves, rats were divided into 5, 15, 25, 38 day-groups and exposed to PEMF (1.5 h/day, intensity; 1.5 mT, consecutive frequency; 10-10-100 Hz). In the 15th day post crush, compound action potential (CAP) amplitude was measured as 5.5 ± 1 mV (crush group) and 5.4 ± 1.2 mV (crush + PEMF group). In addition, half width of CAP extended ∼ 3 fold in both groups and frequency-dependent amplitude inhibition (FDI) decreased -20% at 100 Hz. In the 38th day, amplitude of CAP, half width of CAP and FDI were measured nearly intact nerve values in both groups. In histological examinations, Wallerian degeneration was observed similar progress between both groups. The results were compared between crush and crush + PEMF groups, it was found that the effect of PEMF was not significant. The authors conclude that PEMF were ineffective on rat sciatic nerve regeneration.

Enhanced rat sciatic nerve regeneration through silicon tubes filled with pyrroloquinoline quinone

Pyrroloquinoline quinone (PQQ) is an antioxidant that also stimulates nerve growth factor (NGF) synthesis and secretion. In an earlier pilot study in our laboratory, Schwann cell growth was accelerated, and NGF mRNA expression and NGF secretion were promoted. The present study was designed to explore the possible nerve-inducing effect of PQQ on a nerve tube model over a 1-cm segmental deficit. An 8-mm sciatic nerve deficit was created in a rat model and bridged by a 1-cm silicone tube. Then,10 mul of 0.03 mmol/l PQQ were perfused into the silicone chamber in the PQQ group. The same volume of normal saline was delivered in the control group. Each animal underwent functional observation (SFI) at 2-week intervals and electrophysiological studies at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment, 12 weeks after tube implantation. Using a digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity and amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the PQQ group and controls (P < 0.05). More mature, high-density, newly regenerated nerve was observed in the PQQ group. We conclude that PQQ is a potent enhancer for the regeneration of peripheral nerves.

Structural and Functional Regeneration of Muscle-Related Axons After Transection and Repair of the Rat Sciatic Nerve Using Nonvascularized Autologous Fascia as a Barrier Between Tibial and Peroneal Nerve Fascicles

Aberrant reinnervation of target organs caused by misdirected axonal growth at the repair site is a major reason for the poor functional outcome usually seen after peripheral nerve transection and repair. This study investigates whether the criss-crossing of regenerating rat sciatic nerve axons between tibial and peroneal nerve fascicles can be reduced by using non-vascularized autologous fascia as a barrier. The left sciatic nerve was transected and repaired at midthigh as follows: epineurialy sutures (Group A); fascicular repair of tibial and peroneal nerve fascicles (Group B); fascicular repair of tibial and peroneal nerve fascicles separating the two fascicles by non-vascularized autologous fascia (Group C). In the control Group D, only the left tibial fascicle was transected and repaired. Five months postoperatively, the outcome of regeneration was evaluated by histology, by retrograde tracing, and by assessment of the contraction force of the gastrocnemius and tibial anterior muscles. The tracing experiments showed that muscle reinnervation was less abnormal in Group C than in Groups A and B. However, muscle contraction force was not better in Group C than in Groups A and B. With respect to the peroneal nerve innervated muscle, the contraction force in Group C was significantly lower than in Group B. The histologic picture indicated that this inferior result in Group C was due to nerve compression caused by fibrotic scar tissue at the site of the fascia graft. Results of this study show that a non-vascularized autologous fascial graft used as a barrier between two sutured nerve fascicles in adjacency reduces criss-crossing of regenerating axons between the fascicles, but causes significant nerve compression.

Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve

We have developed an alginate gel crosslinked with covalent bonds for regeneration of dermis, nerve, and bone. Recently, a novel matrix (H/A gel) which consists of heparin and alginate covalently crosslinked with ethylenediamine, was designed. It can stabilize and release biologically active basic fibroblast growth factor (bFGF) for 1 month, which is one of the heparin-binding growth factors. In the present report, we examined the effect of this novel H/A gel on nerve regeneration in the rat sciatic nerve. In this study, regenerated axons in H/A gel with bFGF grew faster than in ordinary alginate gel with bFGF in the early stage. Myelinated fibers showed a tendency to increase in diameter toward the normal size in the later stage. Nerve bundles in the implantation exhibited minimal fibrosis and good vascularization. H/A gel with bFGF exhibited better-developed vascularization than ordinary alginate gel with bFGF. These findings suggested that H/A gel with bFGF could serve not only as an efficient cellular scaffold, but also as a stabilizing matrix for bFGF for peripheral nerve regeneration.

The role of a barrier between two nerve fascicles in adjacency after transection and repair of a peripheral nerve trunk

Aberrant reinnervation of target organs caused by misdirected axonal growth at the repair site is a major reason for the poor functional outcome usually seen after peripheral nerve transection and repair. The following two studies investigate whether criss-crossing of regenerating rat sciatic nerve axons between tibial and peroneal nerve fascicles can be reduced by using a barrier at the coaption site. The left sciatic nerve was transected and repaired at mid-thigh as follows: epineural sutures (group A, A-II), fascicular repair of tibial and peroneal nerve fascicles (group B, B-II), fascicular repair of tibial and peroneal nerve fascicles separating the two fascicles with a pedicled fat flap (group C), Integra® (group D) or non-vascularized autologous fascia (group C-II). In the control groups E and D-II, only the left tibial fascicle was transected and repaired. Four and 5 months postoperatively, the outcome of regeneration was evaluated by histology, by retrograde tracing, and by assessment of the muscle force of the gastrocnemius and tibial anterior muscles. The tracing experiments showed that specificity of muscle reinnervation significantly improved when a barrier was employed, which significantly or clearly improved muscle twitch tension in groups C and D. However, muscle contraction force was not better when fascia was used as barrier. The histological picture indicated that this inferior result in group C-II was due to nerve compression caused by fibrotic scar tissue at the site of the fascia graft. Results of this study show that a pedicle fat flap and Integra® used as barrier significantly prevent aberrant reinnervation between two sutured nerve fascicles in adjacency resulting in improved motor recovery in rats. Non-vascularized autologous fascia however, reduces also criss-crossing of regenerating axons between the fascicles, but causes significant nerve compression.

Electrophysiology and morphometry of the Aα- and Aβ-fiber populations in the normal and regenerating rat sciatic nerve

We studied electrophysiological and morphological properties of the Aα- and Aβ-fibers in the regenerating sciatic nerve to establish whether these fiber types regenerate in numerical proportion and whether and how the electrophysiological properties of these fiber types are adjusted during regeneration. Compound action potentials were evoked from isolated sciatic nerves 12 weeks after autografting. Nerve fibers were gradually recruited either by increasing the stimulus voltage from subthreshold to supramaximal levels or by increasing the interval between two supramaximal stimuli to obtain the cumulative distribution of the extracellular firing thresholds and refractory periods, respectively. Thus, the mean conduction velocity (MCV), the maximal charge displaced during the compound action potential ( Q max), the mean firing threshold ( V 50), and the mean refractory period ( t 50) were determined. The number of myelinated nerve fibers and their fiber diameter frequency distributions were determined in the peroneal nerve. Mathematical modeling applied to fiber recruitment and diameter distributions allowed discrimination of the Aα- and Aβ-fiber populations. In regenerating nerves, the number of Aα-fibers increased fourfold while the number of Aβ-fibers did not change. In regenerating Aα- and Aβ-fibers, the fiber diameter decreased and V 50 and t 50 increased. The regenerating Aα-fibers' contribution to Q max decreased considerably while that of the Aβ-fibers remained the same. Correlation of the electrophysiological data to the morphological data provided indications that the ion channel composition of both the Aα- and Aβ-fibers are altered during regeneration. This demonstrates that combining morphometric and electrophysiological analysis provides better insight in the changes that occur during regeneration.

Methods for the experimental functional assessment of rat sciatic nerve regeneration

In experimental peripheral nerve studies, the rat sciatic nerve model is widely used to examine functional changes after different surgical repairs or pharmacological treatments, following nerve injury. The number and diversity of tests which have been used to assess functional recovery after experimental interventions often makes it difficult to recommend any particular indicator of nerve regeneration. Functional assessment after sciatic nerve lesion has long been focused on walking track analysis, therefore, this article describes in more detail the method to obtain and measure the walking tracks in order to calculate the sciatic functional index (SFI). However, it is important to note that the validity of the SFI has been questioned by several researchers. In addition, the present review includes other traditional tests described in the experimental peripheral nerve literature regarding the rate of return of motor function and sensation, such as the extensor postural thrust (EPT), nociceptive function, and the gastrocnemius-soleus weight parameters. In the last decade, several authors have designed a series of sensitive quantitative methods to assess the recovery of hind limb locomotor function using computerized rat gait analysis. This study aims to review kinematic measures that can be gathered with this technology, including calculation of sciatic functional index, gait-stance duration, ankle kinematics and toe out angle (TOA). A combination of tests, each examining particular components of recovered sensorimotor function is recommended for an overall assessment of rat sciatic nerve regeneration.

Peripheral nerve regeneration using acellular nerve grafts.

Long gap peripheral nerve injuries usually require a graft to facilitate axonal regeneration into the distal nerve stump. The use of autografts is often limited because of graft availability and donor-site morbidity. We investigated whether acellular nerve allografts would provide an appropriate channel for the promotion and induction of sciatic nerve regeneration in rats. Axons sprouted from the proximal portion and reached the distal portion in the 1 cm-long grafts by 1 month. The number of axons in the regenerated nerves was similar to that of normal nerves at 1 month. Loading the grafts with betaNGF and VEGF increased the number and mean diameter of axons and neovascularization in the regenerated nerves at 1 month. The motor conduction velocity increased over time and reached 63 +/- 10% of that of normal nerves at 6 months. The nerve injuries treated with the acellular grafts had a significant improvement in motor, nociception, and proprioception function compared to untreated nerves. The results from this study suggest that acellular nerve allografts may be a useful biomaterial for functional peripheral nerve regeneration.

Carbon dioxide laser-assisted nerve repair: effect of solder and suture material on nerve regeneration in rat sciatic nerve.

In order to further improve and explore the role of lasers for nerve reconstruction, this study was designed to investigate regeneration of sharply transected peripheral nerves repaired with a CO(2) milliwatt laser in combination with three different suture materials and a bovine albumin protein solder as an adjunct to the welding process. Unilateral sciatic nerve repair was performed in 44 rats. In the laser group, nerves were gently apposed, and two stay sutures (10-0 nylon, 10-0 polyglycolic acid, or 25 microm stainless steel) were placed epi/perineurially. Thereafter, the repair site was fused at 100 mW with pulses of 1.0 s. In the subgroup of laser-assisted nerve repair (LANR), albumen was used as a soldering agent to further reinforce the repair site. The control group consisted of nerves repaired by conventional microsurgical suture repair (CMSR), using 4-6 10-0 nylon sutures. Evaluation was performed at 1 and 6 weeks after surgery, and included qualitative and semiquantitative light microscopy. LANR performed with a protein solder results in a good early peripheral nerve regeneration, with an optimal alignment of nerve fibers and minimal connective tissue proliferation at the repair site. All three suture materials produced a foreign body reaction; the least severe was with polyglycolic acid sutures. CMSR resulted in more pronounced foreign-body granulomas at the repair site, with more connective-tissue proliferation and axonal misalignment. Furthermore, axonal regeneration in the distal nerve segment was better in the laser groups. Based on these results, CO(2) laser-assisted nerve repair with soldering in combination with absorbable sutures has the potential of allowing healing to occur with the least foreign-body reaction at the repair site. Further experiments using this combination are in progress.

Enhancement of rat sciatic nerve regeneration by fibronectin and laminin through a silicone chamber.

In this study, the authors examined the effects of fibronectin and laminin on sciatic nerve regeneration in rats. Sixty-eight Sprague-Dawley rats underwent bilateral sciatic nerve transections and silicone tubulizations, with a 10-mm gap between the proximal and distal nerve stumps. Thirty rats (n=30) received 10 microg of fibronectin injection into the right sciatic nerve chamber, while saline was injected into the left nerve chamber, serving as the control. Another 30 rats (n=30) were given 6 microg of laminin injection into the right nerve chambers and saline into the left chambers. At 1, 3, and 4 months postoperatively, electrophysiologic and histologic examinations, including nerve morphometry, were performed. Eight additional rats, receiving fibronectin (n=4) and laminin (n=4) injections, were used for horseradish peroxidase (HRP) tracing at 3 months postoperatively. Results from the study showed that fibronectin- and laminin-treated groups had significantly higher motor nerve conduction velocity and evoked muscle action potential amplitude of the anterior tibial muscle than the control group (p<0.01). Nerve diameter and the number of myelinated axons from the groups receiving fibronectin and laminin applications were greater than the controls (p<0.01). Also, a greater number of HRP-labeled motor neurons were found in the ventral horns and dorsal root ganglia of the fibronectin- and laminin-treatment groups compared to the controls. The authors conclude that local applications of fibronectin and laminin into the nerve chambers can significantly improve axonal regeneration and maturation of injured rat sciatic nerves.

Thyroid hormones stimulate expression and modification of cytoskeletal protein during rat sciatic nerve regeneration

Peripheral neurons can regenerate after axotomy; in this process, the role of cytoskeletal proteins is important because they contribute to formation and reorganization, growth, transport, stability and plasticity of axons. In the present study, we examined the effects of thyroid hormones (T3) on the expression of major cytoskeletal proteins during sciatic nerve regeneration. At various times after sciatic nerve transection and T3 local administration, segments of operated nerves from T3-treated rats and control rats were examined by Western blotting for the presence of neurofilament, tubulin and vimentin. Our results revealed that, during the first week after surgery, T3 treatment did not significantly alter the level of NF subunits and tubulin in the different segments of operated nerves compared to control nerves. Two or 4 weeks after operation, the concentration of NF-H and NF-M isoforms was clearly increased by T3 treatment. Moreover, under T3-treatment, NF proteins appeared more rapidly in the distal segment of operated nerves. Likewise, the levels of βIII, and of acetylated and tyrosinated tubulin isotypes, were also up-regulated by T3-treatment during regeneration. However, only the tyrosinated tubulin form appeared earlier in the distal nerve segments. At this stage of regeneration, T3 had no effect on the level of vimentin expression. In conclusion, thyroid hormone improves and accelerates peripheral nerve regeneration and exerts a positive effect on cytoskeletal protein expression and transport involved in axonal regeneration. These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.

Role of Macrophage Migration Inhibitory Factor (MIF) in Peripheral Nerve Regeneration: Anti-MIF Antibody Induces Delay of Nerve Regeneration and the Apoptosis of Schwann Cells

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine involved in inflammation and immune responses as well as in cell growth. Although we previously demonstrated the presence of MIF in peripheral nerves, and MIF mRNA expression was up-regulated after axotomy, the role of MIF in nerve injury and regeneration has not been evaluated. To examine the potential role of MIF in nerve regeneration, we locally administered an anti-MIF polyclonal antibody into regenerating rat sciatic nerves using the silicone chamber model. The effect of the anti-MIF antibody on nerve regeneration was evaluated using an axonal reflex test. In addition, we carried out a terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) assay and immunohistochemical analysis of the damaged nerve segments with regard to apoptosis-related proteins such as p53 to evaluate the effects of anti- MIF antibodies on apoptosis during the regeneration process. The regeneration length of the nerve in the anti-MIF antibody-treated group was significantly shorter than that in the non-immune rabbit IgG-treated group at weeks 2, 4 and 6 after surgery. TUNEL assay showed that a large number of apoptotic cells, mostly Schwann cells, were observed in the intratubal and distal nerve segments at weeks 4 and 6 after surgery by the anti-MIF antibody treatment. Consistent with these results, Ki-67-positive cells were significantly decreased by the anti-MIF antibody treatment. Immunohistochemical analyses revealed that p53 and, to a lesser extent, Fas were more up-regulated in the anti-MIF antibody-treated nerves than in the controls. Taken together, these results suggest that MIF plays an important role in acceleration of peripheral nerve regeneration and in prevention of Schwann cell apoptosis, mainly through overcoming the apoptotic effect of p53.

30 mm regeneration of rat sciatic nerve along collagen filaments

This paper describes 30 mm regeneration of peripheral nerve axons along collagen filaments; 31-mm-long collagen filaments or collagen tube were grafted to bridge a 30-mm defect of rat sciatic nerve. The mean number and the diameter of regenerated myelinated axons were 330±227 and 2.7±0.9 μm at the distal end of the collagen-filaments 12 weeks postoperatively; while at the distal end of the tube no axon was found.