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PubMed1987

Tissue culture observations relevant to the study of axon-Schwann cell interactions during peripheral nerve development and repair.

During peripheral nerve development the Schwann cell population is expanded so that adequate numbers are available for ensheathment of both nonmyelinated and myelinated nerve fibres. As ensheathment of these fibres progresses each axon--Schwann cell unit becomes surrounded by a basal lamina, providing a unique microtubular framework within the peripheral nerve trunk. Tissue culture studies of pure populations of neurones and Schwann cells cultured separately and in combination indicate that a surface component on the axon provides a mitogenic signal to Schwann cells requiring cell-cell contact. Biochemical, electron microscopic and immunocytochemical analyses of these cultures indicate that Schwann cells in contact with axons are able to generate a basal lamina (containing type IV collagen, laminin and heparan sulphate proteoglycan) and fibrous collagen, without the aid of other cells, and that axonal contact is required for deposition of the basal lamina. The role of Schwann cells and the extracellular matrix they synthesize and organize, as well as the role of the other known products of the Schwann cells in the process of peripheral nerve regeneration, are discussed. It is suggested that the large numbers and advantageous position of the Schwann cells, as well as their ability to provide their own surfaces, a basal lamina and multiple secretory products, may account for their extraordinary ability to foster nerve fibre regeneration.

Animals↗
PubMed2000

[Free nerve transplants in the reconstruction of secondary defects of the peripheral nerves of the hand].

BACKGROUND: Peripheral nerve of the hand significantly participate ub the physiological functions of the hand. A defect in the area of the peripheral nerve therefore represents a problem, the solution of which is in the field of microsurgical reconstruction. The study deals with the possibility of microsurgical reconstruction by use of free nerve draft. SUBJECTIVE: Clinical observation of patients after microsurgical reconstruction of the hand peripheral nerve defect. MATERIAL AND METHODS: 34 patients after lesions of the median nerve, ulnar nerve and mutual impairment of both nerves. The evaluation according the known and spread system system of Medical Research Council, Seddon 1954. RESULTS: We have achieved very good results after isolated lesions of the median nerve, while the results in this, as well a in other groups are better in younger patients and in patients, in whom the devastation of tissue was not too great. Standard results were achieved in the group with isolated injury of the ulnar nerve and the worst results in a small group of concommitant impairment of both median and ulnar nerves. CONCLUSIONS: The results indicate that this method is unambiquously appropriate in such a complicated clinical picture. Our results are in accord with the data from other literature sources. MEANING FOR PRACTICE: Inevitability of specialized centres which would deal with this problem thus reducing the necessity of secondary reconstruction operations and naturally the reduction of financial expenditure or social support provision.

Adolescent↗
PubMed1997

A slowly penetrating interfascicular nerve electrode for selective activation of peripheral nerves.

To meet the future needs of functional electrical stimulation (FES) applications, peripheral nerve electrodes must be able to safely, selectively, and independently stimulate small subpopulations of the axons within a common nerve trunk. A new electrode has been designed to place contacts outside of the perineurium, but within the epineurium of the nerve. This slowly penetrating interfascicular nerve electrode (SPINE) combines the safety and simplicity of extraneural cuff electrodes with the intimate interface of intrafascicular wire and probe electrodes. We briefly discuss a mathematical method of quantifying performance of nerve electrodes based on the functional output of the intact neuromuscular system. The quantification involves three variables: 1) the functional recruitment trajectory (FRT), 2) functional overlap (O), and 3) overall functional selectivity (lambda). Second, we present results from six acute SPINE implants on the feline sciatic nerve. Quantification of stimulation results demonstrate interfascicular stimulation is functionally different than extraneural stimulation in 32 of 38 trials. In 19 of 28 trials, interfascicular stimulation is functionally selective based on depth of penetration and 52 of 58 trials demonstrate selectivity based on the side of the penetrating element. Third, tissue sections show that the SPINE electrode penetrates into the nerve within 24 h without evidence of edema or damage to the perineurium.

Animals↗
PubMed1982

Stereoscopic observation of the microvasculature of peripheral nerves.

The microvasculature of peripheral nerves in dog and human samples was studied by an injection replica scanning electron microscope (SEM) method. The three-dimensional relationship of epineural and intraneural vessels was well demonstrated by this method. Epineural vessels were made of both longitudinal arterioles and venules and also a close meshwork of capillaries. In the intraneural microvasculature, longitudinal arterioles and venules made up the perineural vessels, and grouped capillaries corresponded to the fine vasculature of intrafascicular vessels. Between epineural and intraneural vessels, there was little anastomosis but nutrient arteries ran through the epineural vasculature into the intraneural vessels. There was little interconnection of vessels among the intraneural vasculature. It was postulated that the close meshwork of the epineural layer can resist pressure from outside the peripheral nerves but that longitudinal venules seemed to be affected by pressure and tension at the localized area.

Animals↗
PubMedDate not supplied

[Regeneration and repair of peripheral nerves: clinical implications in facial paralysis surgery].

Peripheral nerve lesions are one of the most frequent causes of chronic incapacity. Upper or lower limb palsies due to brachial or lumbar plexus injuries, facial paralysis and nerve lesions caused by systemic diseases are one of the major goals of plastic and reconstructive surgery. However, the poor results obtained in repaired peripheral nerves during the Second World War lead to a pessimist vision of peripheral nerve repair. Nevertheless, a well understanding of microsurgical principles in reconstruction and molecular biology of nerve regeneration have improved the clinical results. Thus, although the results obtained are quite far from perfect, these procedures give to patients a hope in the recuperation of their lesions and then on function. Technical aspects in nerve repair are well established; the next step is to manipulate the biology. In this article we will comment the biological processes which appear in peripheral nerve regeneration, we will establish the main concepts on peripheral nerve repair applied in facial paralysis cases and, finally, we will proportionate some ideas about how clinical practice could be affected by manipulation of the peripheral nerve biology.

Facial Paralysis↗
PubMed2001

Ambulatory surgery for multi-ligament knee reconstruction with continuous dual catheter peripheral nerve blockade.

PURPOSE: Major reconstructive surgery of the knee traditionally requires an extended hospital stay for pain management. Continuous peripheral nerve blockade is an alternative method of pain control but is seldom used in the ambulatory setting. This case illustrates the use of lumbar plexus and sciatic nerve peripheral catheters for major knee surgery using intermittent bolus dosing for outpatient analgesia. CLINICAL FEATURES: A 20-yr-old male presented for multi-ligamentous knee reconstruction (posterior collateral ligament and revision anterior collateral ligament and lateral collateral ligament). Anesthesia was managed with a lumbar plexus and a sciatic nerve peripheral catheter and a light general anesthetic. Post-operative analgesia was provided with a 12-hr infusion of 0.2% ropivacaine in an over night recovery care centre. Subsequent catheter dosing was performed as an outpatient, twice a day using 0.2% ropivacaine, 10 ml in each catheter (four injections total). This provided 96 hr of analgesia and low supplemental opioid use. CONCLUSION: The use of a lumbar plexus and sciatic nerve peripheral catheter offered an alternative to conventional pain control that worked well in the ambulatory setting. By providing prolonged unilateral lower limb analgesia, extensive knee surgery was performed that would normally require a hospital stay for pain control. Using a bolus dosing method the risk of local anesthetic complications occurring outside of the hospital with a continuous infusion was minimized.

Adult↗
PubMed1997

M. leprae binds to a 28-30-kDa phosphorylated glycoprotein of rat peripheral nerve.

To understand Mycobacterium leprae-peripheral nerve interaction, we have investigated the binding of M. leprae to rat peripheral nerve proteins in an in vitro model using 32P-phosphorylated proteins of the peripheral nerve. Intact M. leprae binds to a major phosphorylated protein of 28-30 kDa and, to a minor extent, to a few proteins of molecular weight 45-55 kDa. This binding was more specific for M. leprae since only insignificant binding was observed with other bacteria, such as M. bovis or Escherichia coli. M. leprae did not show binding to several phosphorylated proteins of the rat brain. The 28-30-kDa binding protein of the rat peripheral nerve was found to be a glycoprotein by concanavalin A-Sepharose column chromatography.

Animals↗
PubMed2002

The effects of rapamycin in murine peripheral nerve isografts and allografts.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.

Animals↗
PubMed2001

Synthesis of leukemia inhibitory factor in injured peripheral nerves and their cells.

The time and site of induction of leukemia inhibitory factor mRNA in injured rat sciatic nerves and its regulation in Schwann cells and fibroblasts from neonatal rat nerves were investigated. Leukemia inhibitory factor mRNA is induced at the lesion site within 6 h of sciatic nerve transection but only after 24 h in the more distal segments. In vitro, interleukin-1beta increases the concentration of leukemia inhibitory mRNA in nerve fibroblasts but not in Schwann cells. Changes in leukemia inhibitory factor mRNA concentration in injured nerves and peripheral nerve cells are similar to those for nerve growth factor mRNA.

Animals↗
PubMed2004

Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-deficient mice.

In myelinated axons, voltage-gated sodium channels specifically cluster at the nodes of Ranvier, while voltage-gated potassium channels are located at the juxtaparanodes. These characteristic localizations are influenced by myelination. During development, Nav1.2 first appears in the predicted nodes during myelination, and Nav1.6 replaces it in the mature nodes. Such replacements may be important physiologically. We examined the influence of the paranodal junction on switching of sodium channel subunits using the sulfatide-deficient mouse. This mutant displayed disruption of paranodal axoglial junctions and altered nodal lengths and channel distributions. The initial switching of Nav1.2 to Nav1.6 occurred in the mutant optic nerves; however, the number of Nav1.2-positive clusters was significantly higher than in wild-type mice. Although no signs of demyelination were observed at least up to 36 weeks of age, sodium channel clusters decreased markedly with age. Interestingly, Nav1.2 stayed in some of the nodal regions, especially where the nodal lengths were elongated, while Nav1.6 tended to remain in the normal-length nodes. The results in the mutant optic nerves suggested that paranodal junction formation may be necessary for complete replacement of nodal Nav1.2 to Nav1.6 during development as well as maintenance of Nav1.6 clusters at the nodes. Such subtype abnormality was not observed in the sciatic nerve, where paranodal disruption was observed. Thus, the paranodal junction significantly influences the retention of Nav1.6 in the node, which is followed by disorganization of nodal structures. However, its importance may differ between the central and peripheral nervous system.

Amino Acid Sequence↗
PubMed1990

Effects of topically administered nerve growth factor on axonal regeneration in peripheral nerve autografts implanted in the spinal cord of rats.

The effect of exogenous nerve growth factor (NGF) on axonal regeneration into autologous peripheral nerve (PN) grafts implanted to the spinal cord (SC) of rats was assessed by retrograde labeling of the parent soma of the regenerating axons with horseradish peroxidase. NGF was delivered at the graft site over periods of 15 and 30 days by using indwelling osmotic minipumps. In control rats, the minipumps were filled with saline. At 15 days after grafting in the NGF-treated rats, the mean number of SC as well as dorsal root ganglion (DRG) neurons that regenerated their axons into the peripheral nerve grafts was increased 55.3 and 26.4 times, respectively, as compared to the control group values. At 30 days, SC and DRG neurons in the NGF-treated group were 10.9 and 3.1 times greater than in the control group. In the NGF-treated group, the regenerating SC neurons were located within a range of 7 to 13 mm from the graft site as compared to 1 to 7 mm in the control group. Finally, the analysis of the soma diameters of the regenerating neurons showed that NGF enhanced and maintained with time the regenerative response from small-sized DRG neurons. Therefore, NGF is thought to promote directly the regenerative potential of SC as well as DRG neurons and to exert an indirect glial cell-mediated effect at the SC-graft interface.

Animals↗
PubMed1998

Schwann cells, neurotrophic factors, and peripheral nerve regeneration.

The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)-beta and their distant relative, glial cell line-derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors.

Animals↗
PubMed2004

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.

Animals↗
PubMed1998

Peripheral nerve reconstruction using freeze-thawed muscle grafts: a comparison with group fascicular nerve grafts in a large animal model.

There is evidence to suggest that the 'freeze-thawed muscle graft' may function as an alternative to established methods of nerve reconstruction. Using a large animal model we compared this method with group fascicular nerve grafting in peripheral nerve reconstruction. We excised a 3 cm segment of right median nerve in 10 anaesthetized sheep. The resulting gaps were repaired with either group fascicular cable grafts (GFCGs) or freeze-thawed muscle grafts (FTMGs). After six months the right (grafted) and left (control) median nerves of each sheep were exposed and assessed for nerve blood flow, nerve conduction velocity and morphological indices of recovery. Nerve blood flow was reduced by 40% in those repaired with FTMGs. All the repaired nerves contained a population of significantly smaller nerve fibres and displayed a reduced peak nerve conduction velocity. Those repaired with FTMGs (mean velocity 30.96 m/s) had a peak velocity significantly faster than the GFCG group (mean 13.16 m/s). This study shows that peripheral nerve reconstruction with freeze-thawed muscle grafts compares well with repair using nerve grafts.

Animals↗
PubMedDate not supplied

Peripheral nerve regeneration, repair, and grafting.

Peripheral nerve injuries are a major source of chronic disability. Advances in microsurgery and a better understanding of nerve healing have greatly improved the outcomes of nerve repair in the past two decades. This paper reviews the current thoughts on peripheral nerve regeneration and repair. Controversial topics such as the timing of nerve repair, new techniques of nerve repair (fibrin glue, lasers, and tubulization), nerve grafting, and the treatment of neuroma are discussed. A general approach to postoperative care is presented and shown to be governed by an understanding of not only nerve healing but tissue healing in general. A summary of current clinical results of upper extremity nerve repairs is given to provide benchmarks of practice for hand therapy units to achieve and supersede.

Hand Injuries↗
PubMedDate not supplied

Long-term peripheral nerve stimulation for painful nerve injuries.

BACKGROUND: Although peripheral nerve stimulation (PNS) has been used in the treatment of pain since 1965, only a few follow-up studies have been published. The aim of the present retrospective study was to carefully assess the long-term efficacy and safety of PNS in the treatment of painful nerve injuries. METHODS: Patients suffering from intractable pain due to peripheral nerve injuries underwent PNS after careful selection. Long-term results were evaluated based upon patients' reports of pain intensity on a visual analog scale (VAS) and their consumption of analgesics. Two categories of results were chosen: good, referring to 50% or more relief of pain with abstinence from analgesic medications; and poor, with less than 50% improvement. RESULTS: Of 154 referred patients, 46 (26 women and 20 men) were found suitable for PNS. Four etiologic factors were identified, the most common being nerve lesion following an operation in the region of the hip or knee. Other etiologies included entrapment neuropathy, pain following nerve graft, and painful neuropathy following a traumatic injection. The follow-up period was 3-16 years. Of the 46 patients who underwent surgery, the results were classified as good in 36 (78%) patients and as poor in 10 (22%) patients. Overall, pain intensity dropped from a VAS of 69 +/- 12 before surgery to 24 +/- 28 postoperatively (P < 0.001). CONCLUSIONS: PNS can produce good pain relief in the majority of carefully selected patients suffering from isolated painful neuropathies.

Adult↗
PubMed2003

Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.

Prolonged delivery of neurotrophic proteins to the target tissue is valuable in the treatment of various disorders of the nervous system. We have tested in this study whether sustained release of nerve growth factor (NGF) within nerve guide conduits (NGCs), a device used to repair injured nerves, would augment peripheral nerve regeneration. NGF-containing polymeric microspheres fabricated from a biodegradable poly(phosphoester) (PPE) polymer were loaded into silicone or PPE conduits to provide for prolonged, site-specific delivery of NGF. The conduits were used to bridge a 10 mm gap in a rat sciatic nerve model. Three months after implantation, morphological analysis revealed higher values of fiber diameter, fiber population and fiber density and lower G-ratio at the distal end of regenerated nerve cables collected from NGF microsphere-loaded silicone conduits, as compared with those from control conduits loaded with either saline alone, BSA microspheres, or NGF protein without microencapsulation. Beneficial effects on fiber diameter, G-ratio and fiber density were also observed in the permeable PPE NGCs. Thus, the results confirm a long-term promoting effect of exogenous NGF on morphological regeneration of peripheral nerves. The tissue-engineering approach reported in this study of incorporation of a microsphere protein release system into NGCs holds potential for improved functional recovery in patients whose injured nerves are reconstructed by entubulation.

Absorbable Implants↗
PubMed2001

[Morphological changes and quantitative DNA analysis of Schwann cells in peripheral nerves after high voltage electrical injury].

OBJECTIVE: To explore the characteristics and the mechanism of the injury of Schwann cells and nerve fibres of the peripheral nerves inflicted by high voltage electricity. METHODS: Rabbits injured by high voltage electricity were employed as the model. Thirty rabbits were randomly divided into control (9) and experimental (21) groups. The dynamic quantitative DNA analysis and the change of the morphology and structure of the sciatic nerve were observed with LM and EM on 0, 3, 7, 10, 14 and 21 postburn days (PBDs), respectively. RESULTS: There was continuous degeneration of the axon and medullary sheath of sciatic nerve tissue and its neogenesis was inhibited. The DNA synthesis in Schwann cell initiated on 3 postburn day (PBD). The distribution of the current was heterogeneous on the cross section of peripheral nerve fibres. CONCLUSION: The obvious features of peripheral nerve injured by high voltage electricity included delayed initiation of the DNA synthesis of Schwann cell and the secondary necrosis and inhibition of neogenesis process of Schwann cell.

Animals↗