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Mechanical properties of acellular peripheral nerve.

BACKGROUND: Acellular nerve has been used in experimental models as a peripheral nerve substitute. Our objective was to determine the difference in tensile strength between fresh and chemically treated acellularized peripheral nerve. MATERIALS AND METHODS: F344 rat sciatic nerves were either fresh or acellularized and tested either whole (Part A) or transected and repaired (Part B). For all constructs, the mean ultimate stress, mean ultimate strain, Young's modulus, and total mechanical work to fracture were calculated. The average ultimate strains for Groups A-1 and A-2 were 0.480 +/- 0.117 and 0.810 +/- 0.114, respectively. The Young's moduli in Groups A-1 and A-2 were 576 +/- 160 and 580 +/- 150 kPa, respectively. In Groups A-1 and A-2, the normalized work to failure was 0.35 +/- 0.14 and 1.11 +/- 0.38 N. The specimens in Group B-1 withstood an average ultimate stress of 780 +/- 280 kPa. The specimens in Group B-2 withstood an average ultimate stress of 405 +/- 20 kPa. RESULTS: The average ultimate strains for Groups B-1 and B-2 were 0.319 +/- 0.087 and 0.266 +/- 0.019, respectively. The Young's moduli in Groups B-1 and B-2 were 4,030 +/- 1360 and 2,290 +/- 280 kPa, respectively. The normalized work to failure in Groups B-1 and B-2 was calculated as 0.22 +/- 0.04 and 0.11 +/- 0.02 N. CONCLUSIONS: Although adequately robust for reconstructive procedures, the acellular peripheral nerve had decreased tensile strength compared with fresh nerve either when tested whole or when transected and repaired.

Animals↗

Blood-flow measurements of injured peripheral nerves by laser Doppler flowmetry.

The effects of injury on peripheral nerve blood flow were studied, using a Laserflo blood perfusion monitor. A total of 11 nerves were studied, five normal and six injured nerves in four patients. Two of the patients had lacerating brachial plexus injuries, and two other patients had compressive neuropathies of their ulnar nerves at the elbow. All of the readings were taken intraoperatively while the patients were undergoing exploration and repair under general anesthesia. Measurements of the damaged nerves were taken serially from the site of injury proximally and distally, by approximating a flexible metric ruler to the dorsal aspect of the nerve along the same axis. In the acutely lacerated injured nerves (3 to 7 days), the measurements were taken at 1, 5, 10, and 20 mm. The maximal amount of retraction in any of the nerves was 1 cm; thus, the overall architecture of the nerves was maintained. In the compressed nerves, measurements were taken at 1, 2 and 3 cm proximal and distal to the medial epicondyle. Measurement of normal undamaged nerves was performed at six different sites along the same axis of the nerve. The averaged results indicate that the normal blood flow ranged from 47 ml/100 g/min to 63 ml/100 g/min, with a mean of 56 ml/100 g/min. In the injured nerves, blood flow was most depressed at sites closest to the laceration, and increased consistently and progressively at sites distant from the injury in both directions.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

What governs the size of the retraction gap in divided peripheral nerves.

The retraction gap in severed peripheral nerves form a part of the critical gap distance. It thus contributes to determining its size. The extent of retraction of severed nerves is variable and depends on joint movements. However, the individual distributions of the retraction gap are more or less constant and remain unaffected in various joint positions. The mean gap size is related to the level of nerve section and it becomes smaller as one moves distally. The degree of retraction increases in a wider, and decreases in a narrower section of the course of the nerves. In consequence of the existing attachments of each nerve to its bed there is inhibition of retraction, but much freer retraction is possible when these attachments are eliminated.

Animals↗

Peripheral nerve lesions: the neuropharmacological outlook.

A review is presented of compounds with trophic effects on the peripheral nervous system. A distinction should be made between three types of effect: enhancement of neurone survival, stimulation of regeneration and induction or stimulation of collateral sprouting. On the basis of data currently available, laminin and insulin-like growth factor I are the most promising substances for regeneration of peripheral nerve lesions. Future investigations of laminin should provide an answer to the query whether local administration facilitates sprouts to cross the gap between proximal and distal nerve stumps. Further experiments are required on effects of systemic administration of IGF-I in animal models of peripheral nerve lesions before investigations can be initiated in man.

Animals↗

Progressive axonopathy: an inherited neuropathy of boxer dogs. Quantitative and morphometric analysis of the peripheral nerve lesion.

Previous studies have described and illustrated the lesions in the peripheral nerves in progressive axonopathy, an inherited neuropathy of Boxer dogs. The present paper assesses these changes using quantitative techniques. Cervical and lumbar nerve roots and tibial, phrenic and medial cutaneous radial nerves have been studied in affected and age-matched normal dogs aged 2 months to 3 years. The dorsal and ventral nerve roots, and to a lesser extent the proximal nerves, contain a proportion of swollen myelinated axons whereas in the middle and distal nerves the larger diameter fibres fail to develop to their expected maximum calibre. The unmyelinated axons remain the same size as those in normal dogs. Myelin sheath changes, with attenuation or loss of the sheath and/or remyelination, become increasingly prevalent through the course of the disease, always maintaining a proximal to distal decrease in their frequency. Quantification indicates that, particularly in the ventral roots, many axons have disproportionately thin sheaths with shortened internodes. Axonal degeneration and regeneration increase in frequency in the distal nerves as the disease progresses. The cervical ventral roots prove an exception in that they contain large numbers of regenerating clusters at most stages. It is suggested that in progressive axonopathy an axonal transport failure may occur in the roots leading to the axonal swellings, as a result of which a developmental hypoplasia occurs in the more distal, larger diameter fibres. The prominent, but unevenly distributed, myelin sheath changes indicate a severe disturbance in axon-sheath cell inter-relationships.

Animals↗

Peripheral nerve injury and regeneration.

The process of nerve regeneration has been studied extensively by traditional morphological methods, but it is only recently that has been possible to identify more precisely the contribution of different nerve subpopulations. By studying different models of nerve repair and regeneration, it is becoming apparent that other tissue components are contributing to the overall process. When muscle grafting is carried out to repair an injured nerve, the regenerating axons are migrating in parallel with Schwann cells to bridge the nerve gap. The presence of Schwann cells is essential for a successful nerve regeneration, most probably because their production of different neuronal trophic factors. This pattern is also repeated when fibronectin mats are used for nerve repair, indicating the possibility to use this new synthetic matrix for clinical application. If the target organ is analysed after nerve repair, the recovery of all nerve components is evident. However, the process occurs at different times in separate skin compartments, and the regeneration of the autonomic innervation appears to be preceded by that of the sensory nerves. When looking at cutaneous nerve regeneration following different type of injury, a common pattern of events becomes apparent. In skin flaps, nerve regeneration begins from the skin surrounding the wound edge, or from the pedicle, and sensory nerves are the first to penetrate into the flap. Angiogenesis precedes reinnervation of the flap, and initially regenerating fibres appear to be associated with newly formed blood vessels. This pattern is evident also in full-thickness wounds and in suction blisters, where only the more superficial cutaneous layer is disrupted. Furthermore, the presence of keratinocytes appears to exert a directional influence on both regenerating blood vessels and nerves, which follow the regenerating keratinocytes when reepidermalisation is taking place. These results would indicate that there is a close relationship between nerve fibres and blood vessels during regeneration, with a substantial contribution to the process from other tissue components and soluble factors from the surrounding environment.

Animals↗

Electrical injuries to peripheral nerves.

As people come frequently into contact with electrical power sources, electrical injuries to peripheral nerves are commonly seen. The authors first review the parameters determining the severity and distribution of electrical injury to nerve tissue. These include tissue resistance, tissue susceptibility, current pathway, type of current, current density, duration and size of electrical contact. Subsequently, the pathophysiology of electrical injuries to nerve tissue is reviewed. Such injuries can be the result of thermal damage, vascular impairment, histological or electrophysiological changes in peripheral nerves, or direct mechanical trauma. Each of these types of injuries causes, specific lesions. As these lesions, especially delayed peripheral neurologic injury, can cause medico-legal problems, it is important to emphasize that electroneuromyography must be performed as early as possible.

Burns, Electric↗

[Functional capacity after peripheral nerve lesion: significance of pain syndromes].

INTRODUCTION: The loss of functional capacity by peripheral nerve lesion is easy to be estimated: A certain neurologic dysfunction results in a characteristic reduction of the former individual capacity. In contrast, the effect of accompanying pain to every-day life and working ability is not known exactly. In this study, we compared the results of judgement in nerve lesions under the circumstances of additional pain syndromes. METHODS: From January 1994 until December 1998 we saw 57 patients with peripheral nerve lesions, part of them with an additional pain syndrome. Beside conventional neurological examination a detailed pain analysis has been done. RESULTS: Lesions of the median or ulnar nerves showed regularly disturbances in neurological functions (10/14 for the median nerve, 13/16 for the ulnar nerve). Astonishing is the fact, that serious pain after nerve lesion only occurs in cases of partial nerve lesion. We saw neuralgias in 6 patients with ulnar neuropathy, in three cases of median nerve lesions we could see severe neuralgia (causalgia we found in 3 cases of ulnar neuropathy, in 6 cases after Median Nerve lesion). Patients with a lesion of the central plexus brachialis showed in 10 of 11 cases an additional pain syndrome. Other nerves have been affected more rarely. For the judgement of the loss of earning capacity we saw an additional pain related diminuition of at least 10% compared to those patients without pain problems. CONCLUSIONS: The common grading scales for peripheral nerve lesions are not suitable in cases accompanied by an additional pain syndrome. Beside a functional deficit the effect of severe pain in these patients has to be estimated. On an average, patients with additional pain-problems get a 10% extended loss of earning capacity, even more in particular cases.

English Abstract↗

Peripheral nerve extract promotes long-term survival and neurite outgrowth in cultured spinal cord neurons.

The hypothesis that peripheral, skeletal muscle tissue contains a trophic factor supporting central neurons has recently been investigated in vitro by supplementing the culture medium of spinal cord neurons with muscle extracts and fractions of extract. We extended these studies asking whether or not a trophic factor is present in peripheral nerves, the connecting link between muscle and central neurons via which factors may be translocated from muscle to neurons by the retrograde transport system. Lumbar, 8-day-old chick spinal cords were dissociated into single cells and then cultured in the presence of peripheral nerve extract. Cytosine arabinoside was added to inhibit proliferation of nonneuronal cells. In the presence of nerve extract, spinal cord neurons survived for more than a month, extended numerous neurites, and showed activity of choline acetyltransferase. In the absence of extract, neurons attached and survived for a few days but then died subsequently in less than 10 days. Neurite outgrowth did not occur in the absence of extract. Withdrawal of extract from the medium of established neuronal cultures caused progressive loss of both cells and neurites. Other tissues also contained neuron supporting activity but less than that found in nerve extract. These studies indicate that peripheral nerves contain relatively high levels of spinal cord neuron-directed trophic activity, suggesting translocation of neurotrophic factor from muscle to central target neurons. The neurotrophic factor has long-term (weeks) effects, whereas short-term (days) survival is factor independent.

Animals↗

Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats.

The purpose of this study was to evaluate the degree of functional recovery in adult rats with completely transected spinal cord following experimental treatment regimens that include implantation of peripheral nerve segments and local application of acidic fibroblast growth factor (aFGF). Rats were randomly divided to five groups: (1) spinal cord transection, (2) spinal cord transection and aFGF treatment, (3) spinal cord transection and peripheral nerve grafts, (4) spinal cord transection, aFGF treatment, and peripheral nerve grafts, and (5) sham control (laminectomy only). The locomotor behavior of all rats was analyzed by the Basso, Beattie and Bresnahan (BBB) open field locomotor test over the six months survival time. Immunohistochemisty for neurofilament protein, and somatosensory (SSEP) and motor evoked potentials (MEP) were used to evaluate axon growth across the damage site following the different treatments. The results show four principal findings: (1) Only the combination of peripheral nerve grafts and aFGF treatment improved hindlimb locomotor function after spinal cord transection. (2) The SSEP and MEP demonstrated electrophysiological evidence of both sensory and motor information crossing the damaged site, but only in the combined nerve grafts and aFGF treatment rats. (3) Immunostaining demonstrated neurofilament positive axons extending through the graft area and into distal end of spinal cord, but only in the group with combined nerve grafts and aFGF treatment. (4) Retransection of group 4 rats eliminated the behavioral recovery, MEP, and SSEP responses, indicating that the improvement of hindlimb locomotor activity came from supraspinal control. These results demonstrate the ability of the repair strategy combining peripheral nerve grafts and aFGF treatment to facilitate the regeneration of spinal ascending and descending tracts and also recovery of motor behavior following spinal cord injury.

Animals↗

Intrathecal morphine reduces allodynia after peripheral nerve injury in rats via activation of a spinal A1 adenosine receptor.

BACKGROUND: The degree to which intrathecally administered morphine can alleviate hypersensitivity in animals after peripheral nerve injury is controversial, and the mechanisms by which morphine works in these circumstances are uncertain. In normal animals, morphine induces adenosine release, and in vitro data suggest that this link is disrupted after peripheral nerve injury. Therefore, using a controlled, blinded study design, the authors tested intrathecal morphine efficacy in rats with peripheral nerve injury and the role of spinal A1 adenosine receptors in the action of morphine. METHODS: Male rats underwent intrathecal catheter implantation and lumbar spinal nerve ligation, resulting in hypersensitivity to tactile stimulation of the paw. Intrathecal morphine alone or with naloxone or the specific A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyxanthine (DPCPX), was administered, and withdrawal threshold to von Frey filament application to the hind paw was determined. RESULTS: Intrathecal morphine (0.25-30 microg) dose-dependently reversed mechanical hypersensitivity after spinal nerve ligation, with an ED50 of 0.79 microg. The effect of morphine was blocked by intrathecal naloxone. Intrathecal DPCPX alone had no effect on withdrawal threshold after spinal nerve ligation but completely reversed the effect of morphine, with an ID50 of 5.6 microg. CONCLUSIONS: This study is in accord with two recent reports that support short-term efficacy of intrathecal morphine to reverse hypersensitivity to mechanical stimuli in animal models of neuropathic pain. Despite previous studies demonstrating that morphine releases less adenosine after peripheral nerve injury, the current study suggests that the antihypersensitivity effect of morphine in these conditions is totally reliant on A1 adenosine receptor activation.

Animals↗

Mutual dependence of murine fetal cutaneous regeneration and peripheral nerve regeneration.

Mammalian fetal cutaneous wounds made at certain developmental stages show complete regeneration. It is reported that wound healing in both adult and fetal skin is disrupted by denervation. Furthermore, fetal cutaneous regeneration has unique aspects such as epidermal wrinkle texture regeneration and dermal regeneration that depend on developmental stage. Therefore, we have examined the relationship of fetal cutaneous regeneration with denervation. We made cutaneous wounds on fetal mice at various developmental time points including embryonic days (E)13, E15, and E17, and compared the regenerating patterns of peripheral nerves in the skin. We found that when the fetuses are wounded at an early stage of development, peripheral nerves regenerate quicker than at later stages of development when peripheral nerve regeneration is delayed. Next, we denervated the intercostal nerves and made wounds at the denervated sites on E13 and E15. We found that epidermal wrinkling and dermal regeneration were disrupted by denervation. These findings indicate that components of fetal cutaneous regeneration and peripheral nerve regeneration are mutually dependent.

Animals↗

Long-term pain control by direct peripheral-nerve stimulation.

In 1970, we began implanting electrodes for prolonged stimulation of injured peripheral nerves to reduce chronic pain. Thirty-eight peripheral nerves in thirty-five patients have been stimulated with electrodes for a period ranging from four to nine years. Nineteen electrode systems were implanted in the upper extremity (eleven on the median nerve, six on the ulnar nerve, one on the median and ulnar nerves, and one on the median and radial nerves), with successful relief of pain in 52..6 per cent of the patients. Sixteen stimulators have been implanted on the sciatic nerve with a success rate for pain relief of 31 per cent. Failures in the lower extremity were found primarily in lesions of the posterior tibial nerve at the ankle. We speculate that the stress of weight-bearing and the anatomical position of the posterior tibial nerve may partially account for this rate of failure. Use of the electrode-implant systems required careful preoperative assessment by an experienced team, meticulous technique, and a mechanical system that tolerates stress. The location and characteristics of the lesion affect the response to electrical stimulation.

Adult↗

Vascular endothelial growth factor expression in peripheral nerves and dorsal root ganglia in diabetic neuropathy in rats.

Vascular alterations of peripheral nerves occuring after mechanical injury or in metabolic disorders are well described. It is thought that vascular endothelial growth factor (VEGF), a potent growth factor for angiogenesis, also plays an important role for regeneration of nervous tissue. We used a rat model of type I diabetes (streptozotozin-induced) with sensory neuropathy and with chronic hyperglycemia over 12 weeks. A monoclonal antibody to VEGF was used for immunohistochemistry of sciatic nerves and dorsal root ganglia (DRG). Intense VEGF staining was detected in cell bodies and nerve fibers of animals with chronic diabetes. Healthy control groups expressed no or very little VEGF and animals treated with insulin to prevent neuropathy and severe hyperglycemia showed significantly lower immunostaining for VEGF. After application of nerve growth factor (NGF), which is known to improve axonal and Schwann cell regeneration, a markedly decreased expression of VEGF was seen in diabetic animals. In contrast, enhanced VEGF staining was noted in NGF-treated healthy controls of the same age and body weight as the diabetic rats. Similar findings were made in diabetic animals treated with both, insulin and NGF. We conclude that functional alteration of peripheral nerves causes up-regulation of VEGF in Schwann cells and neurons. With functional restitution of nervous tissue, i.e. under insulin and/or NGF treatment VEGF expression decreases significantly. Additionally, NGF may stimulate VEGF in normal controls. The production of VEGF may play a role in complete nerve regeneration and its regulation may reflect the functional state of peripheral nerves.

Animals↗

Computer-aided localisation of peripheral nerve lesions.

The clinical localisation of peripheral nerve lesions can sometimes be difficult, particularly following injury to the brachial plexus when multiple lesions are often present. In this situation, computers may be of assistance in interpreting the complicated patterns of clinical findings. This paper describes the evaluation of a computer program that uses a simulation model of the consequences of nerve injury, based on a representation of the relevant anatomy. A retrospective study of 26 patients with upper limb nerve lesions was carried out. The computer program compared favourably with three clinicians in interpreting the findings correctly. It is suggested that this approach may be transferable to other applications.

Arm↗