Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nerve Regeneration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Functional, electrophysiologic, and morphometric evaluation of nerve regeneration from coaptation on regenerated nerve fibers: experimental study in rabbits.

The importance of a sufficient number of nerve fibers at a proximal coaptation site is indisputable for the successful repair of nerves; however, the quality of nerve fibers required at this site has yet to be defined. The present study deals with the question of whether it is necessary to trim nerves back to unaffected neuronal tissue or whether the coaptation on recently regenerated nerve fibers, commonly believed to produce a poor quality of repair can, in fact, produce adequate nerve regeneration. Twenty New Zealand White rabbits received a standardized crush lesion on the peroneal nerves of both hind legs. Four weeks later, the nerves of the left hind legs (n = 20) were transected 10 mm distal to the previous crush lesion and coapted to the freshly regenerated nerve fibers. For comparison, on 10 right hind legs, the nerves were transected at the site of previous crushing (Group A, superimposition) or 10 mm proximal to the site of crushing on unscathed nerve fibers (Group B). Eleven weeks later, the quality of nerve regeneration was assessed by the toe-spreading reflex, electrophysiologic data, muscle weight, and histomorphologic evaluation. In the animals of Group A, the quality of nerve regeneration following coaptation on the regrown axons did not differ in any of the examined parameters from the quality of nerve fibers outgrown from the site of the superimposed lesion. Both lesions led to a completely functional reinnervation. Also in Group B, nerve action potential recording and histologic data on both sides did not reveal a significant difference between the number and maturation of nerve fibers equidistant from the suture site, shortly before muscle entrance. With this coaptation model, it could be demonstrated in the peroneal nerve of rabbits, that coaptation to recently regenerated nerve fibers leads to a significant functional regeneration.

Anastomosis, Surgical↗

Poly lactic acid--caprolactone copolymer tube with a denatured skeletal muscle segment inside as a guide for peripheral nerve regeneration: a morphological and electrophysiological evaluation of the regenerated nerves.

A biodegradable copolymer of poly L-lactic acid and epsilon-caprolactone (PLAC) was manufactured into a tube, in which a denatured skeletal muscle segment was placed longitudinally. This model tube was implanted as a guide to promote nerve regeneration across a 5 cm gap in the rabbit sciatic nerve. Five months after implantation, good nerve regeneration was found throughout the graft and in the distal host nerve. The population (29.6/16 x 10(2) microm(2)) of regenerated nerves in the graft was higher than that of the contralateral normal sciatic nerve (18.0/16 x 10(2) microm(2)). Regenerated nerve fibers extended to the distal host nerve. The number of myelinated fibers was 13.7/16 x 10(2) microm(2) at a level 1.5 cm from the distal suture. The diameters (below 2 microm) of most regenerated myelinated (nerves in the graft and in the distal host nerve were much smaller than those (6-8 microm) of normal nerves. Electrophysiological evaluation showed that the hindlimb muscle (gastrocnemius) was innervated by motor nerves in all animals 5 months after implantation. These results indicate that the PLAC tube with a denatured muscle segment inside provided good conditions for nerve fiber regrowth. The PLAC tube is thought to protect the denatured muscle segment from rapid dissociation in the host tissue.

Absorbable Implants↗

Nerve regeneration in cornea after penetrating keratoplasty in rabbit, with special reference to relationship between regenerating nerves and basal laminae.

The pattern of nerve regeneration in the grafted rabbit cornea was investigated by electron microscopy. Grafted corneas were excised 2, 7, 14 and 28 days after grafting, and processed for observation by conventional electron microscopy. In the normal, unoperated cornea Schwann cell basal laminae are, unlike those of ordinary peripheral nerves, discontinuous and fragmentary on the fibers coursing through the corneal stroma. In the early stage of regeneration, while numbers of regenerating axons extended through the Schwann cell columns of regenerating axons extended through the Schwann cell columns in the grafts, many other regenerating axons elongated as single fibers through the corneal stroma outside the Schwann cell columns. These single naked axons were later enveloped by Schwann cell cytoplasm, contributing to the overall dense irregular pattern of regenerated nerves in the grafted cornea. It was thought that the regenerating axons can extend throughout the stroma without the guidance of basal lamina tubes, making the corneal stroma a favorable environment for nerve regeneration.

Animals↗

Nerve regeneration across a 25-mm gap bridged by a polyglycolic acid-collagen tube: a histological and electrophysiological evaluation of regenerated nerves.

In the study reported here we have examined the nerve regeneration that occurs over a 25-mm gap using a novel biodegradable nerve guide tube. The tube was a composite of polyglycolic acid (PGA) mesh coated with collagen which was filled with neurotrophic factors. The left sciatic nerve of ten adult cats was dissected. The stumps were connected by the tube, and fixed gap. Histological examinations carried out 4-16 months after implantation of the tube revealed regeneration of well vascularized nerve tissue. Regeneration of both myelinated, unmyelinated axons and Schwann cells was confirmed by electron microscopy 5 months after surgery. Following injection of horseradish peroxidase (HRP) into a site peripheral to the regenerated segment of the sciatic nerves, motoneurons in the ventral horn of the spinal cord, afferent terminals in the medial portion of the dorsal column of the medulla oblongata, and sensory afferent nerve terminals in the dorsal horn of the spinal cord were labelled. Electrophysiological examinations revealed restoration of evoked electromyograms and sensory evoked potentials (SEPs) recorded from the cerebral cortex as well as the spinal cord. We also found that some of the regenerated motor axons exhibited branching in the regenerated segments. In two cases, a single motoneuronal axon from the regenerated side projected to both flexors and extensors, simultaneously. Our results indicate that the PGA-collagen composite tube is a promising tool for use as a nerve guide tube in peripheral nerve regeneration.

Animals↗

Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves.

We evaluated peripheral nerve regeneration across an 80-mm gap using a novel artificial nerve conduit. The conduit was made of a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers. Twelve beagle dogs underwent implantation of the nerve conduit across an 80-mm gap in the left peroneal nerve. In four other dogs used as negative controls, the nerve was resected and left unconnected. Histological observation showed that numerous unmyelinated and myelinated nerve fibers, all smaller in diameter and with a thinner myelin sheath than normal nerve fibers, regrew through and beyond the gap 12 months after implantation. The distribution of the regenerated axonal diameters was different from that of the normal axonal diameters. Compound muscle action potentials, motor evoked potentials, and somatosensory evoked potentials were recorded in most animals 3 months after implantation. Peak amplitudes and latencies recovered gradually, which indicating the functional establishment of the nerve connection with the target organs. In addition to the ordinary electrophysiological recoveries, potentials with distinct latencies originating from Aalpha, Adelta and C fibers became distinguishable at the 6th lumbar vertebra following stimulation of the peroneal nerve distal to the gap 12 months after implantation. The pattern of walking without load was restored to almost normal 10-12 months after implantation. Neither electrophysiological nor histological restoration was obtained in the controls. Our nerve conduit can guide peripheral nerve elongation and lead to favorable functional recovery across a wider nerve gap than previously reported artificial nerve conduits.

Animals↗

Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves during IGF-supported nerve regeneration.

Nerve regeneration is augmented by neurotrophic activity, which has long been known to be increased in lesioned nerves. Of identified soluble nerve-derived neurotrophic factors, to date only insulin-like growth factors (IGFs) have been observed to increase the rate of axon regeneration in peripheral nerves. We report that IGF-I and IGF-II mRNA contents were significantly increased (P < 0.0005) distal to the site of crush in rat sciatic nerves, and decreased following axon regeneration. In transected nerves in which axon regeneration was prevented, IGF mRNAs remained elevated. IGF-I mRNAs per mg tissue were increased more in lesioned nerves than denervated muscles, whereas IGF-II mRNAs were increased more in denervated muscles than lesioned nerves. This suggested that IGF-I and IGF-II each play distinct regulatory roles during regeneration. These data bolster the hypothesis that increased IGF mRNA content in nerves supports the rate of nerve regeneration in mammals.

Animals↗

Biomaterials and strategies for nerve regeneration.

Nerve regeneration is a complex biological phenomenon. Once the nervous system is impaired, its recovery is difficult and malfunctions in other parts of the body may occur because mature neurons do not undergo cell division. To increase the prospects of axonal regeneration and functional recovery, researches have focused on designing "nerve guidance channels" or "nerve conduits." When developing ideal tissue-engineered nerve conduits, several components come to mind. They include a biodegradable and porous channel wall, the ability to deliver bioactive growth factors, incorporation of support cells, an internal oriented matrix to support cell migration, intraluminal channels to mimic the structure of nerve fascicles, and electrical activities. This article reviews the factors that are critical for nerve repair, and the advanced technologies that are explored to fabricate nerve conduits. To more accurately mimic natural repair in the body, recent studies have focused on the use of various advanced approaches to create ideal nerve conduits that combine multiple stimuli in an effort to better mimic the complex signals normally found in the body.

Animals↗

Recovery of denervated muscle receptors following treatments to accelerate nerve regeneration.

Nerve regeneration promoters offer the possibility of enhancing recovery following nerve injury by increasing the numbers of regenerating axons and decreasing the period of tissue denervation. To date, recent studies have concentrated on evaluating the action of such promoters on the nerve itself and on the restoration of motor function. This study examines afferent regeneration by evaluating the recovery of muscle spindles and tendon organs after nerve injury and treatment with alpha-melanocyte stimulating hormone or nerve stimulation. Treatment was found to be effective in enhancing short-term recovery after nerve-crush injury in terms of increasing the rate of functional and morphological recovery. Following nerve section, there was an increase in the number of reinnervating axons compared with control values.

Animals↗

Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts.

Previous reports suggest that nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. We compared rabbit facial nerve regeneration in 10-mm silicone tubes prefilled with NGF or cytochrome C (Cyt C), bridging an 8-mm nerve gap, to regeneration of 8-mm autologous nerve grafts. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than Cyt C-treated controls. Morphometric analysis at the middle of the tube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and Cyt C-treated implants. However, when the numbers of myelinated fibers in 5-week regenerates were compared to those in their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than Cyt C-treated implants (46% versus 18%, respectively). The number of regenerating myelinated axons in the autologous nerve grafts at 5 weeks was significantly greater than the number of myelinated axons in the silicone tubes. However, in the nerve grafts the majority of the axons were found in the extrafascicular connective tissue (66%). The majority of these myelinated fibers did not find their way into the distal nerve stump. Thus, although the number of regenerating myelinated axons within the nerve grafts is greater than that of axons within silicone tube implants, functional recovery of autologous nerve graft repairs may not be superior to that of intubational repairs.

Animals↗

Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys.

OBJECTIVE: Nerve regeneration through cold preserved nerve allografts is demonstrated, and treatment of nerve allografts with FK506 induces better regeneration than other immunosuppressants. We study nerve regeneration through cold preserved nerve allografts temporarily treated with FK506 and compare it with the regeneration obtained using classic nerve autografts in a facial paralysis model in monkeys. METHODS: A trunk of the facial nerve on both sides was transected in eight monkeys and immediately repaired with a 3 to 4 cm nerve autograft or allograft. FK506 was administered to the animals of the allograft group for 2 months, and nerve allografts were cold preserved for 3 weeks. At periods of 3, 5, and 8 months after surgery, quantitative electrophysiological assessment and video recordings were performed. At the end of the study, quantitative analysis of neurons in the facial nucleus was carried out, and axons were stereologically counted. RESULTS: After the regenerative period, neuronal density was higher in the autograft group. However, distal axonal counts were similar in both groups. Serial electrophysiological recordings and histology of nerve allografts showed that the grafts were partially rejected after cessation of the immunosuppressant. CONCLUSION: The regeneration through nerve allografts temporarily treated with FK506 does not achieve the electrophysiological results and neuronal counts achieved with nerve autografts, but axonal collateralization in the allografts induces a similar activation of mimic muscles.

Animals↗

Nerve growth factor: increased angiogenesis without improved nerve regeneration.

Nerve growth factor (NGF) and laminin are important factors for neural development and regeneration. We examined the effects of increasing the local concentration and duration of action of NGF and laminin on peripheral nerve regeneration in the adult mouse sciatic nerve. A Silastic (silicone rubber) channel with intraluminal NGF solution was secured between transected nerve ends. The second channel tested, formed from a polysaccharide called chitosan, was prepared with NGF and laminin in the channel walls and provided a sustained release of NGF. At six weeks post-implantation, no improvement in nerve regeneration was identified in those channels prepared with NGF when comparing electromyographic thresholds (microA), maximum potentials (mV), nerve diameter, myelin sheath thickness, myelinated axon counts, or diameter. However, increased angiogenesis was demonstrated within the chitosan and Silastic channels prepared with NGF compared to those channels without NGF. Silastic exhibited minimal inflammation. Chitosan was associated with inflammation in many nerve channels.

Animals↗

Effects of insulin-like growth factor-1 in motor nerve regeneration after nerve transection and repair vs. nerve crushing injury in the rat.

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

Animals↗

4-Methylcatechol, an inducer of nerve growth factor synthesis, enhances peripheral nerve regeneration across nerve gaps.

The effect on peripheral nerve regeneration of 4-methylcatechol (MC), which is a potent inducer of nerve growth factor (NGF) synthesis in vitro and in vivo, was examined in a sciatic nerve-lesioned animal model. The sciatic nerve of adult male Wistar rats was transected and both of the cut ends were then inserted into sterile silicone tubes that were subsequently attached to an intervening silicone chamber. After surgery, the rats were injected i.p. every day for 2 weeks with MC. Two weeks after surgery, the density of nonmyelinated axons within the chamber was significantly increased in the MC-treated group compared with that in the control group. Five weeks after surgery, both the number and the diameter of myelinated axons within the chamber of the MC-treated group were significantly larger than those of the control group. When the chamber was filled with anti-NGF antibody solution, most of the MC effect was blocked. These results suggest that MC stimulates de novo synthesis of NGF (and/or NGF-related molecules), which results in the enhancement of sprouting and maturation of peripheral axons.

Animals↗

The effect of irradiation on nerve regeneration.

Nerve grafts were performed on rat sciatic nerves at varying intervals after the graft bed had been irradiated. The functional repair was assessed electrophysiologically. Five groups of animals were used with the pre-operative interval varying from 1 to 8 weeks. No difference was found in the success of the nerve graft in any group.

Action Potentials↗

Evaluation of peripheral nerve regeneration by nerve growth factor locally administered with a novel system.

An experimental model is presented for the local administration of neurotrophic substances at the site of peripheral nerve lesion. The model consists of a subcutaneously implanted silicone reservoir and a connecting tube with its distal end facing the severed and repaired nerve. Wistar rats (n = 180) were divided into two groups: a control group (saline-treated) (n = 90) and an NGF-treated group (n = 90). After sciatic nerve axotomy, an epineural repair was performed. NGF or saline were injected daily into the subcutaneous reservoir for the first 4 weeks after axotomy and weekly single dose between the 8th and 12th weeks. Both groups were divided into three subgroups of 30 animals each. The animals were sacrificed at 4, 8 and 12 weeks. Myelinated and non-myelinated axonal and thickness of myelin sheaths were quantified at the tibialis branch 25 mm distal to the nerve repair site. Axonal counts showed statistically significant differences between the treated and control groups at 4, 8 and 12 weeks. Finally, at 4 weeks the myelinated axons in the NGF group had significantly thicker myelin sheaths than in the control group. In comparison with other models of administration of different neurotrophic agents, NGF delivered through this system demonstrates a significant capacity for improving nerve regeneration without the problems inherent in multiple anesthesia, device exchange, or short half-life of the NGF single-dose administration.

Animals↗

[Optic nerve regeneration by nerve transplantation].

The optic nerve fibers of adult mammals, once injured, can not regenerate spontaneously. However, from recent studies it has become clear that when their extracellular environment is replaced with that of the peripheral nervous system, namely surrounded with Schwann cells, they can regenerate their axons through the grafted nerve. Previous studies on the optic nerve regeneration by peripheral nerve transplantation have been done mostly in rats or hamsters. With an expectation of clinical application in future, we studied the optic nerve regeneration of adult cats because a great deal of knowledge on the optic nerve fibers and retinal ganglion cells had been accumulated. From recent series of studies we have obtained following results. 1. Retinal ganglion cells that regenerated axons constitute 2--4% of the total population, and among several types of ganglion cells, alpha cells have the greatest capacity for axonal regeneration. The ability of alpha cells for axonal regeneration is related to their relative resistance to axotomy. 2. Retinal ganglion cells with regenerated axons preserve their original dendritic fields, but their axons are thinner than normal, and mostly unmyelinated. 3. Single unit activities recorded from teased fibers of regenerated axons revealed that the units have mostly normal receptive field properties, enabling us to classify them into Y, X or W cells. 4. Amplitude reduction of pattern reversed electroretinogram (ERG) after the optic nerve section was slowed, to some extent, by the peripheral nerve transplantation. How we can reconnect these regenerated optic nerve fibers to the target neurons in the central visual system is a matter for future study.

Animals↗

Nerve regeneration and Schwann cell basal lamina: observations of the long-term regeneration.

Nerve segments approximately 6-7 mm long were excised from the predegenerated sciatic nerves of mice, and treated 5 times by repetitive freezing and thawing to kill the Schwann cells. Such treated nerve segments were grafted into the original place, being in contact with the proximal stump of the sciatic nerve. The animals were sacrificed 2, 3, 5, 7 and 10 days, 2, 3, 5 and 8 weeks after the grafting. The grafts were examined at the middle level, i.e., about 3-4 mm distal to the proximal end of the graft, by light and electron microscopy. Within 2-3 days after the grafting, the dead Schwann cells were disintegrated into fragments and gradually phagocytized by macrophages. However, the basal laminae of the Schwann cells remained as empty tubes (basal lamina scaffolds). The notable finding was that the regenerating axons always grew through these basal lamina scaffolds. New Schwann cells seemed to migrate along these axons from the proximal stumps. The number of axons growing through the basal lamina scaffolds gradually increased with time. These axons were surrounded in a bundle by Schwann cells. About 1 week after the grafting, axons began to be segregated into smaller bundles by Schwann cells. Axons with a relatively large diameter (about 2 microns) tended to be sorted out and surrounded by their own Schwann cells. The myelination began about 2 weeks after the grafting on such large diameter axons. The basal lamina scaffolds, through which the regenerating axons had grown, were gradually disintegrated into fragments by the expansive forces due to the increase in number and volume of the regenerating axons and Schwann cells. Groups of axons, which had been derived from the same basal lamina scaffolds, were enclosed with the cells resembling perineurial epithelial cells. These perineurial epithelial cells proliferated and further separated groups of axons into smaller ones or even into single axons. The number of myelinated axons increased with the advancement of regeneration. These results show that the basal lamina scaffolds of Schwann cells serve as efficient conduits for the elongation, maintenance and maturation of regenerating axons.

Animals↗