Regeneration Of Nerve Fibers Research Articles

Patterns of cutaneous nerve fibre loss and regeneration in type 2 diabetes with painful and painless polyneuropathy.

The determinants and mechanisms of the development of diabetic sensorimotor polyneuropathy as a painful (DSPN+p) or painless (DSPN-p) entity remain unclear. We examined the degree of cutaneous nerve fibre loss and regeneration in individuals with type 2 diabetes with DSPN+p or DSPN-p compared with individuals with recent-onset type 2 diabetes and corresponding healthy volunteers. In this cross-sectional study, skin biopsies taken from the distal lateral calf were obtained from individuals with recent-onset type 2 diabetes (n=32) from the German Diabetes Study, with DSPN+p (n=34) and DSPN-p (n=32) from the PROPANE study, and volunteers with normal glucose tolerance (n=50). Double immunofluorescence staining for protein gene product 9.5 (PGP9.5) (pan-neuronal marker) and growth-associated protein 43 (GAP-43) (nerve regeneration marker) was applied to assess intraepidermal nerve fibre density (IENFD) and length (IENFL) and dermal nerve fibre length (DNFL). DSPN was diagnosed using the modified Toronto Consensus (2011) criteria, while neuropathic pain was assessed using an 11-point Numerical Rating Scale. After adjustment for age, sex, BMI and HbA1c, IENFD and IENFL were reduced for both markers in individuals with recent-onset diabetes and both DSPN groups compared with control participants (all p<0.05), but did not differ between the DSPN groups. The DNFL GAP-43/PGP9.5 ratio was higher in the DSPN+p and DSPN-p groups compared with control participants (1.18±0.28 and 1.07±0.10 vs 1.02±0.10; p≤0.05) and in the DSPN+p group compared with DSPN-p (p<0.05). Correlation analyses showed distinct inverse associations between the DNFL GAP-43/PGP9.5 ratio and PGP9.5 positive IENFD as well as DNFL (IENFD: β=-0.569, DNFL: β=-0.639; both p<0.0001) in individuals with type 2 diabetes, but not in the control group. A similar pattern was found for correlations between the DNFL GAP-43/PGP9.5 ratio and peripheral nerve function tests. Dermal nerve fibre regeneration is enhanced in DSPN, particularly in DSPN+p, and increases with advancing intraepidermal nerve fibre loss. These data suggest that, despite progressive epidermal fibre loss, dermal nerve repair is preserved, particularly in DSPN+p, but fails to adequately counteract epidermal neurodegenerative processes.

Mechanism of ganglioside combined with medical biological adhesive on the regeneration of peripheral nerve after injury

Objective To analysis the mechanism of ganglioside combined with medical biological adhesive on the regeneration of peripheral nerve after injury. Methods Sixty clean grade adult New Zealand white rabbits were selected, either male or female, 10 samples were randomly selected as experimental donors, the sciatic nerve segments were transplanted into the injured sciatic nerve of receiver rabbit, the receiver rabbits were randomly divided into control group and experimental group according to random table, each with 25 rabbits, the corresponding treatment was given to the nerve anastomosis. The levels of nerve conduction function, the morphology of regenerated nerve fibers, the number of myelinated fibers, the diameter of fiber, the thickness of myelin sheath and the diameter of axons, the Guadros index and the micro vascular density (MVD) of rabbits in two groups were detected. Results Compared with rabbit sciatic nerve potential amplitude (4.57±0.61) mV, conduction velocity (22.09±2.59) m/s, conduction latency (2.47±0.35) ms in control group after 12 weeks, levels of rabbit sciatic nerve potential amplitude (5.51±0.74) mV, conduction velocity (28.95±3.27) m/s in the experimental group were higher, conduction latency (2.01±0.26) ms were lower (t/P: 2.401/0.020, 4.028/0.000, 2.584/0.020). Compared with after 4 weeks, the number of myelinated fibers (2 744.38±324.37), fiber diameter (14.29±2.04) μm, the thickness of myelin sheath (7.04±0.89) μm, axon diameter (4.39±0.48) μm, the number of myelinated fibers of 8 weeks (2 043.32±276.58), fiber diameter (11.58±1.48) μm, myelin sheath the thickness of (6.11±0.63) μm, axon diameter (4.15±0.41) μm and the number of myelinated fibers of 12 weeks (1 475.44±206.39), fiber diameter (9.32±1.14) μm, the thickness of myelin sheath (4.29±0.58) μm, axon diameter (3.11±0.36) μm in the control group, levels of 4 weeks the number of myelinated fibers (3 629.72±502.12), fiber diameter (18.47±2.41) μm, the thickness of myelin sheath (9.87±1.36) μm, axon diameter (5.45±0.52) μm, the number of myelinated fibers of 8 weeks (2 704.38±319.47), fiber diameter (16.98±2.24) μm, the thickness of myelin sheath (8.03±1.12) μm, axon diameter (5.09±0.58) μm and the number of myelinated fibers of 12 weeks (2 242.43±279.48), fiber diameter (15.63±2.23) μm, the thickness of myelin sheath (6.82±0.72) μm, axon diameter (4.76±0.49) μm in the experimental group were higher (t/P: 3.628/0.000, 3.832/0.000, 5.408/0.000, 3.243/0.000, 4.265/0.000, 3.669/0.000, 4.927/0.000, 3.660/0.000, 3.242/0.000, 6.171/0.000, 6.703/0.000, 6.647/0.000). Compared with the control group of 4 weeks (0.31±0.04), 8 weeks (0.33±0.04) and 12 weeks (0.35±0.05), the experimental group of4 weeks (0.46±0.06), 8 weeks (0.48±0.06) and 12 weeks (0.52±0.07), and the Guadros index was higher (t/P: 5.095/0.000, 5.095/0.000, 4.841/0.000). Compared with the control group of 8 weeks (12.95±1.71) and 12 weeks (29.49±3.87), The experimental group of 8 weeks (28.64±3.84) and 12 weeks (45.83±6.15) MVD count was higher (t/P: 8.835/0.000, 26.400/0.000). Conclusion Topical application of ganglioside combined with medical biological adhesive can improve the nerve conduction function of peripheral nerve after injury, restore the number and morphology of nerve fibers, prevent muscle atrophy, promote the formation of new blood vessels, so as to promote nerve regeneration. Key words: Ganglioside; Medical biological adhesive; Peripheral nerve regeneration; Mechanism

Repair of nerve injury by implanting prostheses obtained from isogenic acellular nerve segments

IntroductionWhen a nerve section with a significant gap occurs, it is necessary to use a prosthesis to suture it. To date an autologous nerve segment graft appears to be the best treatment; but it has several important disadvantages. Our goal is to study the effectiveness of an isogenic acellular nerve prosthesis comparing a simple suture with tubulisation. Material and methodFour groups of Wistar rats were used. The animals in Group 0 served as donors of nerve segments to graft. Group 1 received the implant with an end-to-end suture. In Group 2, the implant was sutured inside an ɛ-caprolactone tube. Group 3 received it in a polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index and step test in motion), and the regeneration length by histological study of regeneration, after a maximum of 3 weeks. ResultsRegeneration was uneven in the three groups. In all groups, there were implants with regenerated nerve fibres at the maximum studied length (15mm) and others where regeneration was scarce. The mean regeneration length was greater in the direct end-to-end suture group (G1), although the regeneration speed was similar in the three groups. Group 1 showed the highest percentage of regeneration, but the variability of results prevents this difference reaching statistical significance. We found no significant differences between the two groups with polymer tubes. ConclusionFor the implantation of isogenic acellular nerve prosthesis, under our experimental conditions, the direct end-to-end suture was more effective than when it is protected with biopolymer tubes.

Automatic tool for quantification of nerve fibres in corneal confocal microscopy images

SummaryFailure after failure of phase 3 clinical trials in diabetic neuropathy has led to the realisation that potentially effective treatments have failed because of inadequate end‐points in clinical trials. Our pioneering studies showed that corneal confocal microscopy (CCM) had excellent diagnostic potential in diabetic somatic and autonomic neuropathy. We and others subsequently used CCM to diagnose peripheral neuropathies in obesity, impaired glucose tolerance, hereditary neuropathy (CMT1A, Friedreich's ataxia), Fabry's disease, amyloid neuropathy, CIDP, HIV etc. Of significant potential as a surrogate end‐point, we have shown that CCM detects nerve fibre regeneration within 6 months of pancreas transplantation in diabetic patients and after 24 months of an improvement in glycaemic control, blood pressure and lipids, continuous subcutaneous insulin infusion and after bariatric surgery. We have shown nerve repair in several phase 2b trials of ARA290, a peptide derivative of erythropoietin, in patients with sarcoid neuropathy and diabetic neuropathy. We have also shown that CCM detects axonal pathology which relates to the severity of neurological deficits in patients with Parkinson's disease, multiple sclerosis and dementia.

Reparación de lesiones en nervios mediante el implante de prótesis obtenidas de segmentos acelulares de nervio isogénico

IntroductionWhen a nerve section with a significant gap occurs, it is necessary to use a prosthesis to suture it. To date an autologous nerve segment graft appears to be the best treatment; but it has several important disadvantages. Our goal is to study the effectiveness of an isogenic acellular nerve prosthesis comparing a simple suture with tubulisation. Material and methodFour groups of Wistar rats were used. The animals in Group 0 served as donors of nerve segments to graft. Group 1 received the implant with an end-to-end suture. In group 2, the implant was sutured inside an ɛ-caprolactone tube. Group 3 received it in a polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index and step test in motion), and the regeneration length by histological study of regeneration, after a maximum of 3 weeks. ResultsRegeneration was uneven in the three groups. In all groups, there were implants with regenerated nerve fibres at the maximum studied length (15mm) and others where regeneration was scarce. The mean regeneration length was greater in the direct end-to-end suture group (G1), although the regeneration speed was similar in the three groups. Group 1 showed the highest percentage of regeneration, but the variability of results prevents this difference reaching statistical significance. We found no significant differences between the two groups with polymer tubes. ConclusionFor the implantation of isogenic acellular nerve prosthesis, under our experimental conditions, the direct end-to-end suture was more effective than when it isprotected with biopolymer tubes.

Mast cells improve functional recovery of transected peripheral nerve: A novel preliminary study

BackgroundEmployment of regenerative properties of cells at the service of nerve repair has been initiated during recent decades. Effects of local transplantation of bone marrow-derived mast cells on peripheral nerve regeneration were studied using a rat sciatic nerve transection model. Materials and methodsA 10-mm sciatic nerve defect was bridged using a conduit chitosan-based hybrid conduit filled with BMMCs in BMMC group. In positive control group (Pos), the conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied within 12 weeks after surgery. In sham-operated group, the sciatic nerve was only exposed and manipulated. In negative control (Neg) a 10-mm sciatic nerve defect was created and the nerve stumps were sutured to the adjacent muscles. The regenerated nerve fibers were studied functionally, biomechanically, histologically and immunohiscochemically. ResultsFunctional and biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to Pos group (p<0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in Pos group (p<0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in Pos group. ConclusionsBMMCs transplantation could be considered as a readily accessible source of cells that could improve functional recovery of transected sciatic nerve.

Repair of the musculocutaneous nerve using the vagus nerve as donor by helicoid end-to-side technique: an experimental study in rats.

Although several donor nerves can be chosen to repair avulsed brachial plexus nerve injury, available nerves are still limited. The purpose of this study is to validate whether the vagus nerve (VN) can be used as a donor. Eighteen Sprague-Dawley male rats were divided into three groups (n = 6). The right musculocutaneous nerve (McN) was transected with differing subsequent repair. (1) HS-VN group: a saphenous nerve (SN) graft-end was helicoidally wrapped round the VN side (epi-and perineurium was opened) with a 30 ° angle, distal SN end was coapted to the McN with end-to-end repair. (2) EE-PN group: a SN was interpositionally grafted between the transected phrenic nerve (PN) and the McN by end-to-end coaptation. (3) Sham control group: McN was transected and not repaired and postoperative vital signs were checked daily. At three months, electrophysiology, tetanic force, wet biceps muscle weight, and histology were evaluated. Every tested mean value in HS-VN group was significantly greater than the EE-PN or the sham control groups (p < 0.05 or p < 0.005). The mean recovery ratio of regenerated nerve fibers was 96% and, in HS-VN group, the mean recovery ratio of CMAP was 79%. No vital signs changed in any group. There was no statistical difference (p > 0.5) between the mean VN nerve-fiber numbers of the segments proximal (2237 ± 134) and distal (2150 ± 156) to the VN graft-attachment site. Histological analysis revealed no axon injury or intraneural scarring at any point along the VN. This study demonstrated that VN is a practical and reliable donor nerve for end-to-side nerve transfer. © 2017 Wiley Periodicals, Inc.

Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) remains one of the most common and serious complications of diabetes. Currently, pharmacological agents are limited to treating the pain associated with DPN, and do not address the underlying pathological mechanisms driving nerve damage, thus leaving a significant unmet medical need. Interestingly, research conducted using exercise as a treatment for DPN has revealed interleukin-6 (IL-6) signaling to be associated with many positive benefits such as enhanced blood flow and lipid metabolism, decreased chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known solely as a pro-inflammatory cytokine, is now understood to signal as a multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory responses in a context-dependent fashion. IL-6 released from muscle in response to exercise signals as a myokine and as such has a unique kinetic profile, whereby levels are transiently elevated up to 100-fold and return to baseline levels within 4 h. Importantly, this kinetic profile is in stark contrast to long-term IL-6 elevation that is associated with pro-inflammatory states. Given exercise induces IL-6 myokine signaling, and exercise has been shown to elicit numerous beneficial effects for the treatment of DPN, a causal link has been suggested. Here, we discuss both the clinical and preclinical literature related to the application of IL-6 as a treatment strategy for DPN. In addition, we discuss how IL-6 may directly modulate Schwann and nerve cells to explore a mechanistic understanding of how this treatment elicits a neuroprotective and/or regenerative response. Collectively, studies suggest that IL-6, when administered in a low-dose pulsatile strategy to mimic the body’s natural response to exercise, may prove to be an effective treatment for the protection and/or restoration of peripheral nerve function in DPN. This review highlights the studies supporting this assertion and provides rationale for continued investigation of IL-6 for the treatment of DPN.

Management of diabetic neuropathy: the ADA's latest statement fleshes out NICE guidance

Management of diabetic neuropathy: the ADA's latest statement fleshes out NICE guidance

Morphometrical and histological evaluation of the effect of vitamins B1, B6 and B12 on rats sciatic nerve after crush injury

Objectives: To evaluate the effect of vitamins (B1, B6, and B12) on nerve regeneration and recovery after crush injury to sciatic nerve in experimental rats Study Design: Prospective observational study Setting: Department of anatomy, College of medicine,Baghdad University Subjects and intervention: Total 60 Rats ,with ageing(8-12) weeks old of both sex, during 45 days period were included in this study Study period: 15 October 2016 to 30 November 2016 Results: on comparision among different groups ( control and experimental groups ) . Best improvement in group of rats on B12(group D) than other groups on B1(groupB) or B6(group C). B12 group treated with ( 1mg / kg / day ) significantly increased in the MTC when compared to the control , B6 and B1 groups on days 15, 30 and 45 of the study at P≤0.05. Histological analysis by Van Giesons stain,A- all groups control and experimental (B1,B6,B12,A) show degeneration in different areas but less in group B12. B- sciatic nerve fascicles with Schwann cell and fibroblast better organized in group B12 Conclusion: vitamin B12, among different kind of vitamins B, considered as a best vital medication for regeneration and remyelination of damage nerve fibers.

Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury.

Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results.

Impaired Axonal Regeneration in Diabetes. Perspective on the Underlying Mechanism from In Vivo and In Vitro Experimental Studies.

Axonal regeneration after peripheral nerve injury is impaired in diabetes, but its precise mechanisms have not been elucidated. In this paper, we summarize the progress of research on altered axonal regeneration in animal models of diabetes and cultured nerve tissues exposed to hyperglycemia. Impaired nerve regeneration in animal diabetes can be attributed to dysfunction of neurons and Schwann cells, unfavorable stromal environment supportive of regenerating axons, and alterations of target tissues receptive to reinnervation. In particular, there are a number of factors such as enhanced activity of the negative regulators of axonal regeneration (e.g., phosphatase and tensin homolog deleted on chromosome 10 and Rho/Rho kinase), delayed Wallerian degeneration, alterations of the extracellular matrix components, enhanced binding of advanced glycation endproducts (AGEs) with the receptor for AGE, and delayed muscle reinnervation that can be obstacles to functional recovery after an axonal injury. It is also noteworthy that we and others have observed excessive neurite outgrowth from peripheral sensory ganglion explants from streptozotocin (STZ)-diabetic mice in culture and enhanced regeneration of small nerve fibers after sciatic nerve injury in STZ-induced diabetic rats. The excess of abortive neurite outgrowth may lead to misconnections of axons and target organs, which may interfere with appropriate target reinnervation and functional repair. Amelioration of perturbed nerve regeneration may be crucial for the future management of diabetic neuropathy.

Ultrasound-Enhanced Molecular Therapy for Axon Neurogenesis

Between 28M - 55M individuals experience spinal cord injuries (SCIs). In the U.S. alone, this amounts to an estimated 180k-230k individuals. In the central nervous system (CNS) after an injury to a nerve, the environment prevents the healing/regrowth of neurons and myelin, because myelin inhibitors are present, growth factor is not re-expressed, and glial tissue scars very quickly. Knowing that nerves need to be regenerated quickly, research has been done to discover an optimal treatment for nerve regeneration. Unfortunately, no effective method currently exists to stimulate nerve fiber regeneration (i.e., neurogenesis). To address this gap, we propose a non-invasive method to stimulate neurogenesis through low-intensity focused or unfocused ultrasound irradiation. This method is new and has high potential as a transformative rehabilitation approach for people with disabilities due to SCIs. A combination of therapeutic methods that mitigate the inhibitory microenvironment at the site of the injury and restore the regeneration potential of corticospinal axons are required for achieving effective functional recovery after SCI. We developed an in vitro system integrating focused ultrasound (FUS) with neuron axon dynamics for neurogenesis and an approach using a 3D microenvironment. Dorsal root ganglion (DRG) neurons are used for our studies and microsurgically removed at day 15 and E18 Sprague Dawley cortical neurons from BrainBits, LLC. To determine if stimulation of axon growth is occuring, we measure density and growth (distance) using phase contrast imaging and a custom MATLAB code for image analysis. We tested a variety of operating parameters to identify optimal conditions that induce axon neurogenesis by ultrasound. We demonstrated that ultrasound can stimulate DRGs.

VEGF-B promotes recovery of corneal innervations and trophic functions in diabetic mice

Vascular endothelial growth factor (VEGF)-B possesses the capacity of promoting injured peripheral nerve regeneration and restore their sensory and trophic functions. However, the contribution and mechanism of VEGF-B in diabetic peripheral neuropathy remains unclear. In the present study, we investigated the expression and role of VEGF-B in diabetic corneal neuropathy by using type 1 diabetic mice and cultured trigeminal ganglion (TG) neurons. Hyperglycemia attenuated the endogenous expression of VEGF-B in regenerated diabetic corneal epithelium, but not that of VEGF receptors in diabetic TG neurons and axons. Exogenous VEGF-B promoted diabetic corneal nerve fiber regeneration through the reactivation of PI-3K/Akt-GSK3β-mTOR signaling and the attenuation of neuronal mitochondria dysfunction via the VEGF receptor-1 and neuropilin-1. Moreover, VEGF-B improved corneal sensation and epithelial regeneration in both normal and diabetic mice, accompanied with the elevated corneal content of pigment epithelial-derived factor (PEDF). PEDF blockade partially abolished trophic function of VEGF-B in diabetic corneal re-innervation. In conclusion, hyperglycemia suppressed endogenous VEGF-B expression in regenerated corneal epithelium of diabetic mice, while exogenous VEGF-B promoted recovery of corneal innervations and trophic functions through reactivating PI-3K/Akt-GSK-3β-mTOR signaling, attenuating neuronal oxidative stress and elevating PEDF expression.

Effect of hierarchically aligned fibrin hydrogel in regeneration of spinal cord injury demonstrated by tractography: A pilot study

Some studies have reported that scaffold or cell-based transplantation may improve functional recovery following SCI, but no imaging information regarding regeneration has been provided to date. This study used tractography to show the regenerating process induced by a new biomaterial-aligned fibrin hydrogel (AFG). A total of eight canines subjected to SCI procedures were assigned to the control or the AFG group. AFG was implanted into the SCI lesion immediately after injury in 5 canines. A follow-up was performed at 12 weeks to evaluate the therapeutic effect including the hindlimb functional recovery, anisotropy and continuity of fibers on tractography. Using tractography, we found new fibers running across the SCI in three canines of the AFG group. Further histological examination confirmed limited glial scarring and regenerated nerve fibers in the lesions. Moreover, Repeated Measures Analysis revealed a significantly different change in fractional anisotropy (FA) between the two groups during the follow-up interval. An increase in FA during the post injury time interval was detected in the AFG group, indicating a beneficial effect of AFG in the rehabilitation of injured axons. Using tractography, AFG was suggested to be helpful in the restoration of fibers in SCI lesions, thus leading to promoted functional recovery.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects.

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10-30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the 'multiple amplification' phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect.

Short-term observations of the regenerative potential of injured proximal sensory nerves crossed with distal motor nerves.

Motor nerves and sensory nerves conduct signals in different directions and function in different ways. In the surgical treatment of peripheral nerve injuries, the best prognosis is obtained by keeping the motor and sensory nerves separated and repairing the nerves using the suture method. However, the clinical consequences of connections between sensory and motor nerves currently remain unknown. In this study, we analyzed the anatomical structure of the rat femoral nerve, and observed the motor and sensory branches of the femoral nerve in the quadriceps femoris. After ligation of the nerves, the proximal end of the sensory nerve was connected with the distal end of the motor nerve, followed by observation of the changes in the newly-formed regenerated nerve fibers. Acetylcholinesterase staining was used to distinguish between the myelinated and unmyelinated motor and sensory nerves. Denervated muscle and newly formed nerves were compared in terms of morphology, electrophysiology and histochemistry. At 8 weeks after connection, no motor nerve fibers were observed on either side of the nerve conduit and the number of nerve fibers increased at the proximal end. The proportion of newly-formed motor and sensory fibers was different on both sides of the conduit. The area occupied by autonomic nerves in the proximal regenerative nerve was limited, but no distinct myelin sheath was visible in the distal nerve. These results confirm that sensory and motor nerves cannot be effectively connected. Moreover, the change of target organ at the distal end affects the type of nerves at the proximal end.

Tissue-engineered nerve graft with tetramethylpyrazine for repair of sciatic nerve defects in rats

A tissue-engineered nerve with tetramethylpyrazine (TMP) was repaired for sciatic nerve defects in rats. A total of 55 adult Sprague Dawley (SD) rats were classified into 4 groups, with 15 rats in each of groups A, B, and C as well as 10 rats in group D. About 1.5cm of a sciatic nerve of the right hind limb located 0.5cm below the inferior margin of the piriformis was resected to form the defects. Four types of nerve grafts used for bridging nerve defects in the SD rats corresponded to the 4 groups: tissue-engineered nerves with TMP in group A, tissue-engineered nerves without TMP in group B, acellular nerve grafts (ANGs) in group C, and autologous nerves in group D. Twelve weeks post-surgery, the sciatic functional index, nerve conduction velocity, and gastrocnemius wet weight of groups A and D were higher than those of groups B and C (P<0.05). Results of fluorescence microscopy and histological staining indicated that group A performed better than groups B and C (P<0.05). Similarly, the number of horseradish peroxidase-labeled positive cells was significantly larger in group A than in groups B and C. Regenerative nerve fibers were abundant in group A and consisted mainly of myelinated nerve fibers, which were better than those in groups B and C (P<0.05). The study demonstrated that tissue-engineered nerves constructed by ANGs seeded with neural stem cells and combined with TMP can effectively repair sciatic nerve defects in rats.

To reverse or not to reverse? A systematic review of autograft polarity on functional outcomes following peripheral nerve repair surgery.

The literature describing the best clinical practice for proximal-distal autograft orientation, otherwise known as nerve graft polarity, is inconsistent. With existing disparities in the peripheral nerve literature, the clinical question remains whether reversing nerve autograft polarity bears an advantage for nerve regeneration. A comprehensive review of the literature using Embase and PubMed databases (1940-June 2015) was performed to retrieve all original articles on the effects of nerve autograft polarity on nerve regeneration and functional recovery following primary repair of peripheral nerve defects. The initial database search yielded 318 titles. Duplicate exclusion, title review and full text review yielded six articles which directly compared nerve autograft polarity. Histological, morphometric, electrophysiological, and behavioral outcomes were reviewed. All retained articles were animal studies, of which none demonstrated significant differences in outcomes between the normal and reversed polarity groups. A reversed graft may ensure that regenerating nerve fibers are not lost at branching points, however this may not translate into improved function. There is insufficient data to suggest that nerve autograft polarity has an impact on nerve regeneration and functional outcomes.

Study of olfactory ensheathing cells transplantation and treadmill training on improving hindlimb motor function of spinal cord injury rats

To investigate the effects of olfactory ensheathing cells (OECs) transplantation and treadmill training in improving hindlimb motor function of spinal cord injury(SCI) rats and explore its possible mechanism. A total of 80 male SD rats were randomly divided into four groups: media untrained (group A), OECs untrained (group B), media trained (group C) and OECs trained(group D). Each group had 20 rats and all rats were made the model of spinal cord injury. The rats of group C and D underwent treadmill exercise in 3 days after operation, the rats of group B and D underwent OECs transplantation in 7 days after operation (each rat was injected a total of 4 μl, cell concentration was 1.0×10₆/μl), at the same time, the rats of group A received the corresponding dose of saline. Then observed was continued for 4 weeks totally. BBB scores in each group were measured weekly. The expression of Bax, Bcl-2, NF-200 were observed by immunohistochemisty staining. Mallory staining was used to the regeneration of nerve fibers and TUNEL staining was used to observe neuronal apoptosis. (1)The BBB scores in group D in the 4th week was significantly higher than of other three groups(P<0.05). (2)On the Bcl-2 protein expression, there was interaction between OECs and treadmill training, the two mutually reinforcing;while OECs transplantation can significantly reduce the Bax protein expression without significant interaction with treadmill training(P>0.05). TUNEL staining showed that OECs transplantation, treadmill training, the time factor had an interaction and significantly inhibited the apoptosis(P<0.05). (3)It was showed in immunohistochemisty staining of NF-200 and Mallory staining that OECs transplantation, treadmill training with the time factor were an interaction among the three with significant regeneration of nerve fibers(P<0.05). OECs transplantation combined with treadmill training can significantly improve hindlimb motor function of SCI rats, which may be achieved by the following ways. OECs transplantation and treadmill training can collaborate with each other, significantly increasing the expression of Bcl-2 gene, which significantly inhibit neuronal apoptosis;at the same time it can promote neuronal axonal regeneration, increase the number of nerve fibers, and this effect may be more remarkable with time.