Why It Is Necessary to Use the Entire Root rather than Partial Root When Doing Contralateral C7 Nerve Transfer: Cortical Plasticity Also Matters besides the Amount of Nerve Fibers.

Previous studies suggested that the mode of donor transection is a critical factor affecting the efficacy of the contralateral C7 (CC7) nerve transfer. Nevertheless, the mechanism underlying this phenomenon remains elusive. The aim of this study was to investigate the relationship between the division modes of the CC7 nerve and cortical functional reorganization of Sprague-Dawley rats. We hypothesized that different methods of CC7 nerve transection might induce differences in cortical functional reorganization, thus resulting in differences in surgery efficacy. BDNF, TNF-α/IL-6, and miR-132/134 were selected as indicators of cortical functional reorganization. No significant differences in all these indicators were noted between the entire group and the entire root+posterior division group (P > 0.05). BDNF and miR-132/134 levels in the entire group and the entire root+posterior division group were significantly increased compared with their levels in the posterior group and the blank control group (P < 0.001). In all groups, BDNF, TNF-α/IL-6, and miR-132/134 levels in both hemispheres initially increased and subsequently decreased until week 40. In conclusion, this study provided the evidence of dynamic changes in BDNF, TNF-α/IL-6, and miR-132/134 in the cortex of rats after CC7 nerve transfer using different transecting modes, demonstrating that different CC7 nerve divisions might result in different surgical effects through modulation of cortical reorganization.

[Restoration of damaged cortical pathways by neural grafting]. / Restauration des voies corticales lésées par greffe de neurones.

The motor cortex plays a central role in the control, planning, and execution of voluntary motor commands in mammals. The loss of cortical neurons is a common feature of many neuropathological conditions such as traumatic and ischemic lesions or several neurodegenerative diseases. Cell transplantation presents a promising therapeutic strategy to overcome the limited abilities of axonal regrowth and spontaneous regeneration of the adult central nervous system. In this review, we will present a historical review of brain transplantation and the current state of research in the field of cortical transplantation.

Corneal Neurotization With a Great Auricular Nerve Graft: Effective Reinnervation Demonstrated by In Vivo Confocal Microscopy.

PURPOSE: We describe the first case of minimally invasive corneal neurotization with the great auricular nerve (GAN) to treat unilateral neurotrophic keratopathy. We assessed corneal sensation and reinnervation by esthesiometry and confocal microscopy over 12 months of follow-up, and we provide a detailed description of the surgical technique. METHODS: Corneal neurotization was successfully achieved with the ipsilateral GAN in a 58-year-old woman. Cochet-Bonnet esthesiometry and in vivo confocal microscopy were performed before and after corneal neurotization, to monitor the recovery of corneal sensation and corneal reinnervation by subbasal nerve fibers. RESULTS: Neurotrophic keratopathy was a complication of the surgical treatment of meningioma. Before surgery, the patient had no corneal sensation or corneal innervation. Six months after surgery, confocal microscopy confirmed regrowth of a large number of nerve fibers in the subepithelial space of the cornea. Nine months after surgery, a central esthesiometry score of 10-mm was attained. CONCLUSIONS: Corneal neurotization leads to reinnervation of the cornea and recovery of ocular sensation in adults. The GAN is suitable for use in corneal neurotization because of its anatomical proximity and the low level of associated morbidity. Confocal microscopy demonstrated the occurrence of corneal reinnervation, which preceded the recovery of corneal sensation.

Reparación de lesiones en nervios mediante el implante de prótesis obtenidas de segmentos acelulares de nervio isogénico / Repair of nerve injury by implanting prostheses obtained from isogenic acellular nerve segments

Introducción. Cuando se produce una sección nerviosa con separación significativa de los cabos es necesario utilizar una prótesis, a modo de puente, para suturarlos. La mejor prótesis es un segmento de nervio autógeno, pero presenta importantes inconvenientes. Nuestro objetivo es comparar la eficacia de la sutura simple con la tubulización para el implante de una prótesis de nervio isogénico descelularizado. Material y método. Se utilizan 4 grupos de ratas Wistar. Grupo 0: animales donantes de nervio ciático. Grupo 1: recibió el implante con sutura término-terminal. Grupo 2: recibió el implante dentro de un tubo de ??-caprolactona. Grupo 3: lo recibió en un tubo de poliláctico-co-glicólico. Se evaluó la función motora (índice ciático) y la extensión de la regeneración (estudio histológico) a las 3 semanas del implante. Resultados. La regeneración ha sido irregular en los 3 grupos experimentales. En todos hay implantes en los que las fibras nerviosas regeneran la longitud máxima estudiada (15mm) y otros en los que la regeneración es muy escasa. La longitud media de regeneración es mayor en el grupo de sutura directa (G1), aunque la velocidad es similar en los 3. El grupo 1 muestra el mayor porcentaje de regeneración, aunque la variabilidad de los resultados impide que esta diferencia alcance significación estadística. No hemos hallado diferencias significativas entre los dos grupos con tubos de diferentes polímeros. Conclusión. Para implantar prótesis de nervios isogénicos descelularizados es más eficaz, en nuestras condiciones experimentales, la sutura término-terminal que los tubos de polímeros biocompatibles (AU)

Introduction. When 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 method. Four 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 ??-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. Results. Regeneration 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. Conclusion. For 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 (AU)

Autologous nerve implantation into denervated monkey skin promotes regeneration of Meissner's corpuscle.

BACKGROUND: The aim of this study was to observe the effects of autologous nerve implantation into the denervated finger flap on the regression and regeneration of sensory nerve endings and Meissner's corpuscles. MATERIAL/METHODS: Bilateral nerves of fingers were separated: one was removed and the other was implanted into the denervated finger in the implantation group. In the non-implantation group, both nerves were removed. The ventral skin of fingers was collected for immunohistochemistry and electron microscopy 3, 6, 9 and 12 months after surgery. RESULTS: The nerve endings in the Meissner's corpuscles began to degenerate 3 months after denervation. The elementary structure of Meissner's corpuscles was not significantly altered. Nerve fibers were present around the Meissner's corpuscles, accompanied by growing into its inward. The axons in the denervated nerve disappeared and the Meissner's corpuscles began to atrophy at month 6. More regenerated nerve fibers were observed after nerve implantation, including intensive and thick fibers, accompanied by reinnervation of Meissner's corpuscles. More nerve fibers and a higher proportion of myelinated nerve fibers were noted at month 9 in the implantation group, and the reinnervation was present in the majority of Meissner's corpuscles. Naive myelinated nerve fibers appeared at the caudal end of Meissner's corpuscles. The nerve fibers in the Meissner's corpuscles increased to the normal level at 12 months after nerve implantation. CONCLUSIONS: The implanted nerve regenerated a large amount of free nerve endings, which helped to regenerate simple Meissner's corpuscles via governing previously degenerated corpuscles.

Plexiform neurofibroma of the upper limb / Neurofibroma plexiforme de membro superior

The authors present an unusual case of plexiform neurofibroma affecting the upper limb in a patient diagnosed with type 1 neurofibromatosis. Tumor resection was performed on the median nerve. The patient showed maintenance of limb function and remission of symptoms of pain after four years of follow-up.

Os autores apresentam um caso incomum de neurofibroma plexiforme acometendo o membro superior, com diagnóstico de neurofibromatose do tipo 1. Realizou-se a ressecção do tumor no nervo mediano. A paciente evoluiu com manutenção da função do membro e remissão dos sintomas de dor após seguimento de quatro anos.

Nerve endoneurial microstructure facilitates uniform distribution of regenerative fibers: a post hoc comparison of midgraft nerve fiber densities.

Despite their inferiority to nerve autograft, clinical alternatives are commonly used for reconstruction of peripheral nerve injuries because of their convenient off-the-shelf availability. Previously, our group compared isografts with NeuraGen(®) (Integra, Plainsboro, NJ) nerve guides, which are a commercially available type I collagen conduit and processed rat allografts comparable to Avance(®) (AxoGen, Alachua, FL) human decellularized allograft product. From this study, qualitative observations were made of distinct differences in the pattern of regenerating fibers within conduits, acellular allografts, and isografts. In the current post hoc analysis, these observations were quantified. Using nerve density, we statistically compared the differential pattern of regenerating axon fibers within grafts and conduit. The conduits exhibited a consistent decrease in midgraft density when compared with the isograft and acellularized allografts at two gap lengths (14 mm and 28 mm) and time points (12 and 22 weeks). The decrease in density was accompanied by clustered distribution of nerve fibers in conduits, which contrasted the evenly distributed regeneration seen in processed allografts and isografts. We hypothesize that the lack of endoneurial microstructure of conduits results in the clustering regenerating fibers, and that the presence of microstructure in the acellularized allograft and isografts facilitates even distribution of regenerating fibers.

Nerve grafts with various sensory and motor fiber compositions are equally effective for the repair of a mixed nerve defect.

Autologous, cellular nerve grafts are commonly used to bridge nerve gaps in the clinical setting. Sensory nerves are most often selected for autografting because of their relative ease of procurement and low donor site morbidity. A series of recent reports conclude that sensory isografts are inferior to motor and mixed nerve isografts for the repair of a mixed nerve defect in rat. The aim of the present study was to determine if the disparity reported with cellular graft subtypes exists for detergent decellularized, chondroitinase ABC processed nerve grafts. We hypothesized that processing removes or neutralizes the inferior properties attributed to sensory nerve grafts. Saphenous (cutaneous branch), femoral quadriceps (muscle branch) and tibial (mixed trunk) nerve grafts 5 mm in length were used in tensionless reconstruction of syngenic rat tibial nerves. Nerve regeneration through the grafts and into the recipient distal nerve was evaluated 21 days after grafting by two methods, toluidine blue staining of semi-thin sections (myelinated axons) and neurofilament-immunolabeling (total axons). Contrary to previous reports using this grafting scheme, we found no significant difference in the myelinated axon counts for the three cellular graft subtypes. Moreover, total axon counts indicated cellular saphenous nerve grafts were more effective than the quadriceps and tibial nerve grafts. A similar though less pronounced trend was found for the decellularized processed grafts. These findings indicate that nerve graft composition (sensory and motor) has no substantial impact on the short-term outcome of nerve regeneration in a mixed nerve repair model.

[Effects of tripterygium glycoside on apoptosis of the skeletal muscle after nerve allograft].

OBJECTIVE: To explore the effect of tripterygium glycoside (TG) on the skeletal muscle atrophy and apoptosis after nerve allograft. METHODS: Twenty Wistar male rats were adopted as donors, weighing 200-250 g, and the sciatic nerves were harvested. Fifty SD male rats were adopted as recipients, weighing 200-250 g. Fifty SD rats were made the models of 10 mm right sciatic nerve defect randomly divided into five groups (n=10): group A, group B, group C, group D and group E. groups A and B received fresh nerve allograft, groups C and D received sciatic nerve allograft pretreated with TG, and group E received autograft. The SD rats were given medicine for 5 weeks from the second day after the transplantation: groups A and E were given physiological saline, groups B and D TG 5 mg/(kg x d), and group C TG 2.5 mg/(kg x d). At 3 and 6 weeks, respectively, after nerve transplantation, general observation was performed; the structure of skeletal muscles was observed by HE staining; the diameter of skeletal muscles was analyzed with Image-Pro Plus v5.2; the ultrastructure of skeletal muscles was observed by TEM; the expressions of Bax and Bcl-2 were detected by immunohistochemical staining; and the apoptosis of skeletal muscles was detected by TUNEL. RESULTS: All rats survived to the end of the experiment. In general observation, the skeletal muscles of SD rates atrophied to different degrees 3 weeks after operation. The muscular atrophy in group A was more serious at 6 weeks, and that in the other groups improved. The wet weight, fiber diameter and expression of Bcl-2 in group A were significantly lower than those in groups B, C, D and E (P < 0.01); those in groups B, C and D were lower than those in group E (P < 0.05); and there were no significant differences among groups B, C and D (P > 0.05). The apoptosis index and expression of Bax in group A were significantly higher than those in groups B, C, D and E (P < 0.01); those in groups B, C and D were higher than in group E (P < 0.05); and there were no significant differences among groups B, C and D (P > 0.05). Three weeks after nerve allograft, under the light microscope, the muscle fibers became thin; under the TEM, the sarcoplasmic reticulum was expanded. Six weeks after nerve allograft, under the light microscope, the gap of the muscle fibers in group A was found to broaden and connective tissue hyperplasia occurred obviously; under the TEM, sarcomere damage, serious silk dissolution and fragmentary Z lines were seen in group A, but the myofibrils were arranged tidily in the other groups, and the light band, dark band and sarcomere were clear. CONCLUSION: TG can decrease the skeletal muscle atrophy and apoptosis after nerve allograft. The donor's nerve that is pretreated with TG can reduce the dosage of immunosuppressant for the recipient after allograft.

[A long-term study of regeneration of mechanical sensory fibers after free nerve transplantation to the rabbit reconstructed penis].

OBJECTIVE: To explore the regeneration of mechanical sensory fibers after free nerve transplantation. METHOD: Neuroelectrophysiological technique (single nerve fiber recording) was used to test the regeneration rate of mechanical sensory fibers, the proportion of rapidly and slowly adapting receptors, the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers. The regeneration pattern of the mechanoreceptors after free nerve transplantation to the rabbit reconstructed penis was also analyzed. RESULTS: 9 months after operation, the number of regenerated mechanical sensory fiber was almost normal. The regenerated rapidly adapting receptors had a higher proportion with higher mature degree than the regenerated slowly adapting receptors. 9 months after nerve transplantation the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers remained below normal. CONCLUSION: After free nerve transplantation to the rabbit reconstructed penis, the function of both rapidly and slowly adapting sensory nerve fiber partially recovered, but in different extent.

Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats.

Previous studies have indicated that the nigrostriatal dopaminergic (DA) pathway can be reconstructed in hemiparkinsonian rats with a bridge transplantation technique involving fetal ventral mesencephalic transplants and glial cell line-derived neurotrophic factor. In this study, we examined if the nigrostriatal pathway can be restored by combining peripheral nervous tissue with the fetal ventral mesencephalon transplants. Adult rats were injected with 6-hydroxydopamine into left median forebrain bundle. Those with marked rotational behavior, which has been previously shown to indicate complete DA dennervtion, were used for transplant treatments. One month after the lesion, fetal ventral mesencephalic cells were transplanted into the nigral region followed by nigral-striatal grafting of peripheral nerves as a bridge. The bridging nerves (sciatic or intercostals) were pretreated with basic fibrous growth factor (nerve+bFGF+) or Hank's saline (nerve+bFGF-). We found that (a) animals receiving transplants of VM and bFGF+ nerve had a reduction in rotational behavior; (b) animals receiving bFGF-- nerve bridge only had a partial improvement in rotation. Reinnervation of tyrosine hydroxylase (TH)-immunoreactive (ir) fibers into the striatum was found in both of the above groups with more innervation in the former than in the latter. No TH-ir fibers in lesioned striatum or reduction in rotational behavior were found in animals receiving VM only, or VM plus bFGF. Taken together, our data indicate that peripheral nerve, with the aid of bFGF, greatly facilitates the reconstitution of the TH pathway from nigra to striatum and improves motor function in hemiparkinsonian rats.

[An effect of the peripheral nerve allograft with subcutaneous preservation at different times on the nerve regeneration].

OBJECTIVE: To study an effect of the peripheral nerve allograft with subcutaneous preservation at different times on the sciatic nerve regeneration in rats. METHODS: Fifty-five Wistar rats were used in this experiment, which were randomly divided into the following 5 groups: the experimental groups (Groups A, B, C, 10 rats), the control group (Group D, 10 rats), and the donor group (Group E, 15 rats). In the experimental groups, a 15-mm segment of the sciatic nerve harvested from the donors was separately inserted into the subcutaneous compartment on the left thigh after the 1-week (Group A), 2-week (Group B), and 3-week (Group C) preservation; the segment of the sciatic nerve in the subcutaneous compartment was removed and transplanted into a 10-mm defect of the right sciatic nerve, which was made immediately. In Group D, a 10-mm sciatic nerve defect was made and immediately repaired in situ on the right thigh. The function of the sciatic nerve was evaluated by the sciatic functional index (SFI) at 2, 4, 6, 8, 10 and 12 weeks after operation. The histological and electrophysiological examinations were performed at 12 weeks after operation. RESULTS: After operation, SFI decreased gradually at 12 weeks after operation, SFI in Groups A and D was at the minimal level and had a significant difference compared with that in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. A large number of the myelinated nerve fibers and a small number of the unmyelinated nerve fibers were regenerated in Groups A and D. The number and the structure of the regenerated nerve were similar to the normal ones. The number and the size of the regenerated axon had a significant difference compared with those in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. The conduction velocity and the latent period of the motor nerve had significant differences between Groups A and D and Groups B and C (P < 0.05), and there was no significant difference between Group A and Group D. CONCLUSION: The nerve allograft with a 1-week subcutaneous preservation can promote nerve regeneration better.

Physiological and clinical advantages of median nerve fascicle transfer to the musculocutaneous nerve following brachial plexus root avulsion injury.

OBJECT: Loss of biceps muscle function is a significant disability after brachial plexus root avulsion injuries. Nerve grafting techniques to reestablish anatomical and functional continuity between the spinal cord and the avulsed root have not proven successful. Using nerve transfers for functional restoration of root avulsion injuries appears to be effective and has physiological advantages for reducing regeneration distances. Since the early 1990s, the Oberlin technique of transferring ulnar nerve fascicles to the motor branch of the musculocutaneous nerve has been the preferred operative technique for reinnervation and restoration of biceps muscle function. In the current study the authors examine the efficacy of an alternative technique using median nerve fascicles transferred to the musculocutaneous nerve to reinnervate the biceps muscle. METHODS: Forty consecutive patients with combined C5-6 brachial plexus root avulsions were evaluated pre- and postoperatively according to the British Medical Research Council Motor Grading Scale. Personal interviews concerning quality of life (QOL) after surgery were conducted and scored based on standards set by the World Health Organization. All patients showed some degree of improvement in biceps muscle function. Thirty-six (90%) of the 40 patients regained movement against gravity. The patients had a 77% improvement in overall QOL after the surgery; most notably, 92% of the patients reported their lack of need for medication and 75% a significant lessening of postoperative pain. Redirection of part of the healthy median nerve resulted in no measurable functional deficits, and only 28 patients reported minor sensory disturbances in the first web space for an average of 3 months after surgery. CONCLUSIONS: Median nerve fascicle transfer resulted in a significant improvement in biceps muscle function with an acceptable level of morbidity and should be considered an effective, and in many cases preferable, alternative to ulnar nerve fascicle transfer.

FK506 and anti-CD40 ligand in peripheral nerve allotransplantation.

PURPOSE: Immunomodulatory agents are often combined in organ transplantation to minimize toxicity and enhance therapeutic effect. We hypothesized that combining low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration through peripheral nerve allografts while preserving immune unresponsiveness. METHODS: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506 (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25 mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were performed. RESULTS: Animals receiving low-dose FK506 with anti-CD40L mAb exhibited robust nerve regeneration comparable to the isograft and high-dose FK506 allograft groups. Nerve density was significantly increased in the low-dose FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-gamma production was markedly elevated in untreated allografts compared to all other treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose FK506 alone group and suppressed in all remaining groups. CONCLUSION: When combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without disrupting immune unresponsiveness.

Morphological variations in brachial plexus of beagle dogs: evaluation of utility as sources of allogeneic nerve grafts.

Basic studies were carried out to apply frozen allogeneic nerve grafts in dogs after wide-ranging defects of the brachial plexus due to surgical resection of tumor. In this study, morphological variations in branching patterns of the brachial plexus were examined in ten beagle dogs, to evaluate whether the brachial plexus might represent a useful source of allogeneic nerve grafts. Spatial relationships between the axillary lymph node, which had the possibility of carcinomatous metastasis, and the musculocutaneous (MC) nerve, which was important for the function of the forelimbs, were also investigated. In all ten cases examined, the brachial plexus received ventral roots from the fifth cervical nerve to the first thoracic nerve. No significant variation in the branching pattern was found in any nerve except the phrenic, MC and dorsal thoracic nerves. Four communicating branches were observed and had some morphological variations which might be negligible for nerve grafting. Considering previous physiological and anatomical reports, the most important nerve to be reunited in graft operations for functional recovery is the radial nerve. The MC nerve and median or ulnar nerve should also be considered as possibilities for reuniting. Distances between the axillary lymph nodes and the MC nerve ranged from 11.2 mm to 21 mm (mean +/- SD: 16.1 +/- 2.3 mm). In conclusion, it was suggested that morphological variations in the brachial plexus were technically acceptable to apply allogeneic nerve grafts at least in beagle dogs.

How do transplanted olfactory ensheathing cells restore function?

In this article, we review our work on regeneration of the corticospinal tract in rats following a lesion at upper cervical level. We outline the rationale for using olfactory ensheathing cells, and summarize the evidence for regeneration and functional recovery. The present interpretation on the mechanisms of functional recovery is partly hypothetical, and we emphasize where further experimental evidence is needed.