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PubMed1975

Peripheral nerve injury as a complication of axillary arteriography.

Five patients with peripheral nerve injury after axillary arteriography are presented. The clinical and electromyographic pictures of this complication are described. In 4 patients the brachial plexus was damaged due to haematoma or pseudoaneurysm-formation at the site of the arterial puncture. The grave prognosis for this complication is illustrated on the basis of the literature and our cases. Since it is concluded that the prognosis is better if rapid surgical correction of the complication is performed, certain steps to prevent the disabling outcome are proposed.

Adolescent↗
PubMed2000

Guided regeneration with resorbable conduits in experimental peripheral nerve injuries.

Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Artificial conduits can be constructed from biodegradable polymers. Lactic/caproic acid copolymers and polyphospazenes are biocompatible materials with a slow resorption rate. Conduits made from either poly-[1-lactide-co-6-caprolatone] or poly-[bis-(ethylalanate)-phosphazene] were assessed for use as guides for nerve regeneration in experimental animals. Under general anesthesia and by using a microsurgery technique both sciatic nerves were exposed in 2 groups of 9 Wistar rats. On the right side, a 10 mm segment of the nerve was removed, and the defect was then repaired using a conduit. On the left side, the same defect was bridged using as an autograft the nerve segment, which had been removed from the right sciatic nerve. Histological and electron microscopy investigations were performed after 30, 90 and 180 days and showed the gradual degradation of both types of conduits without any evidence of local toxicity. The regeneration of the nerve fibers in the lumen was not significantly different from that shown by the autologous grafts. Likewise, no differences were found at 180 days in the functional recovery of the nerve (evoked muscle action potential). Both conduits were found to be effective for guided nerve regeneration. Poly-[1-lactide-co-6-caprolactone] tubes were easier to insert, while polyphosphazene conduits allowed the use of neurite-promoting factors.

Animals↗
PubMed1982

Regenerative processes in peripheral nerve injury: a new method for their evaluation.

The objective of this study was to evaluate a new quantitative electrophysiologic method and instrumentation for assessing the regenerative process in peripheral nerve injuries. The method was based on spectrum analysis of myoelectric signals. Myoelectric data were obtained longitudinally from affected muscles of the upper limb in patients with traumatic brachial plexus injuries, and quantitatively subjected to on-line analysis. Bipolar surface recordings were made during voluntarily mediated motor unit activity at both a low level of activity (nonfatiguing state) and a maximal level (fatiguing state). The results over time for the low-level activity have shown a significant increase in mean frequency of the myoelectric signal in some muscles, a significant decrease in other muscles, and no change in still other muscles. A significant increase in amplitude was observed in every instance. During the maximal level of activity there was a reduction in mean frequency and the amount of reduction was shown to increase over time. The results are useful in indicating the occurrence of peripheral sprouting, axonal regrowth, of central reorganization, and in indicating improved metabolic activity in a muscle. It is concluded that the method is reliable in the study of the regenerative process.

Electrophysiology↗
PubMed2002

Spinal norepinephrine release from nitric oxide species is not increased following peripheral nerve injury in rats.

Alpha(2)-Adrenergic agonists increase the synthesis of nitric oxide (NO) in the spinal cord in both in vitro slice perfusion and in vivo microdialysis. In the normal condition, inhibition of NO synthase (NOS) has little effect on antinociception from alpha(2)-adrenergic agonists. However, following peripheral nerve injury, NOS inhibitors completely block the antihypersensitivity effects of alpha(2)-adrenergic agonists. It is possible that this increased reliance on NO may reflect a positive feedback release of norepinephrine (NE) stimulated by NO conjugates. For example, both S-nitroso-l-cysteine (SNC) and 6-NO(2)-norepinephrine (6-NO(2)-NE) release NE in rat spinal synaptosomes in a concentration-dependent manner and both are formed in spinal cord in vivo. In the current study, we tested whether SNC and 6-NO(2)-NE induced spinal NE release is increased in animals with peripheral nerve injury compared to normals. Crude spinal cord synaptosomes were prepared from nerve ligated and normal rats, loaded with [(3)H]NE and incubated with SNC or 6-NO(2)-NE. In a separate experiment, spinal cords from both groups were sonicated and the amount of NE measured using HPLC. NE release stimulated by SNC or 6-NO(2)-NE in lumbar dorsal spinal cord tissue did not differ between normal and nerve ligated groups. This suggests that increased spinal NE release from locally produced SNC or 6-NO(2)-NE is not the mechanism underlying the reliance of alpha(2)-adrenergic agonists on NO following peripheral nerve injury. Increased NE content and trend towards greater NE uptake in nerve injured spinal cord are consistent with increased noradrenergic innervation density of the spinal cord following peripheral nerve injury.

Animals↗
PubMed1998

Expression of nerve growth factor in the dorsal root ganglion after peripheral nerve injury.

Nerve growth factor (NGF) is believed to play a critical role in altering the phenotypic and functional properties of dorsal root ganglion (DRG) cells after a pathological insult. The present study examined NGF protein levels and NGF immunoreactivity (NGF-IR) in the DRG at multiple time points following peripheral nerve injury. The NGF protein level in the ipsilateral DRG decreased dramatically at 6 h after the injury, but recovered to an almost normal level at 2 days. In accordance with the NGF level, the proportion of NGF-IR neurons also showed a significant decrease at 6 h after the injury, but recovered to the normal level at 3 days. In addition, NGF-IR can also be found in satellite cells at a time point of 3 days after the injury. These data suggest that there is an increase in synthesis of NGF within the DRG after peripheral nerve injury, which contributes to the recovery of NGF levels. The newly synthesized NGF may play important roles in the reactions of DRG neurons to peripheral nerve injury.

Animals↗
PubMed1992

Spatiotemporal increases in epidermal growth factor receptors following peripheral nerve injury.

Non-neuronal cells of peripheral nerve respond to axonal injury with a series of cellular changes that facilitate neuronal regeneration. To characterize the potential role of the epidermal growth factor (EGF) family of proteins in this response, we monitored the expression of EGF receptor mRNA and protein in the injured rat sciatic nerve. EGF receptor mRNA is synthesized in both primary cultured fibroblasts and Schwann cells, and Schwann cells express EGF receptor-like immunoreactivity. In situ hybridization and immunocytochemistry revealed that EGF receptor mRNA and protein are expressed in Schwann cells and fibroblasts of the sciatic nerve in vivo, and that receptor levels increase following nerve injury. Thirty-six hours postlesion, EGF receptors were expressed in gradients along the nerve both proximal and distal to the lesion, with the highest levels localized adjacent to the transection site. By 72 hr, receptor levels were maintained in a gradient in the proximal segment, but were uniformly increased throughout the portions of the distal segment that were analyzed. These changes were similar to those observed for low-affinity NGF receptor mRNA and protein, with transection causing increased expression in both Schwann cells and fibroblasts. Northern blots confirmed that primary cultured fibroblasts express low-affinity NGF receptor mRNA. To determine whether spatiotemporal gradients were a general characteristic of the nerve injury response, we monitored expression of the mRNA encoding the major myelin protein P0. Levels of P0 mRNA decreased initially in cells immediately adjacent to the transection site and, by 72 hr, were uniformly decreased throughout the distal segment. These data suggest that members of the EGF family of proteins may play a role in the peripheral nerve response to injury, and demonstrate a generalized gradient of cellular responses that commence at the transection site and progress distally in the nerve in the absence of intact axons.

Animals↗
PubMed2005

Electrophysiologic evaluation of peripheral nerve injuries in children following the Marmara earthquake.

The aim of this study was to investigate the clinical, demographic, and electromyographic (EMG) characteristics of 12 earthquake victims in the pediatric age group and to compare the findings with those of the adult group. Following the 1999 Marmara earthquake, 75 subjects with suspected peripheral nerve injury were referred to our EMG laboratory for evaluation. In the pediatric age group, five patients had a history of short-term temporary trauma and seven had a history of being trapped under the debris for 4 to 10 hours and sustaining long-term trauma. Five patients had developed compartment syndrome and one had developed crush syndrome. The EMG examinations revealed peripheral nerve injury findings in all patients. The brachial plexus was damaged in 2 patients, and 19 peripheral nerves were damaged in 10 patients. Peroneal and posterior tibial nerves were predominantly affected. Regeneration was detected in all of the patients with brachial plexus damage at a mean follow-up of 3.5 months and in 62.5% of patients with peripheral nerve damage at a mean follow-up of 7.7 months. Being buried under the debris, compartment syndrome, peripheral nerve injuries in the lower extremities, and total axonal damage in the first EMG examinations were found to be higher in the pediatric age group. Regeneration findings were found at similar rates in both groups, with the brachial plexus being the most favorable. When it is considered that the regeneration process lasts 15 to 18 months and EMG findings mostly show pathologies in the form of neuropraxia and axonotmesis, we think that the prognosis of our patients will be good.

Adolescent↗
PubMed2003

Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury.

Over a half a century of research has confirmed that neurotrophic factors promote the survival and process outgrowth of isolated neurons in vitro. The mechanisms by which neurotrophic factors mediate these survival-promoting effects have also been well characterized. In vivo, peripheral neurons are critically dependent on limited amounts of neurotrophic factors during development. After peripheral nerve injury, the adult mammalian peripheral nervous system responds by making neurotrophic factors once again available, either by autocrine or paracrine sources. Three families of neurotrophic factors were compared, the neurotrophins, the GDNF family of neurotrophic factors, and the neuropoetic cytokines. Following a general overview of the mechanisms by which these neurotrophic factors mediate their effects, we reviewed the temporal pattern of expression of the neurotrophic factors and their receptors by axotomized motoneurons as well as in the distal nerve stump after peripheral nerve injury. We discussed recent experiments from our lab and others which have examined the role of neurotrophic factors in peripheral nerve injury. Although our understanding of the mechanisms by which neurotrophic factors mediate their effects in vivo are poorly understood, evidence is beginning to emerge that similar phenomena observed in vitro also apply to nerve regeneration in vivo.

Animals↗
PubMed1998

p75 and TrkA neurotrophin receptors in human skin after spinal cord and peripheral nerve injury, with special reference to sensory corpuscles.

Human skin, including nerves and sensory corpuscles, displays immunoreactivity (IR) for low- (p75) and high-affinity (TrkA-like) receptors for nerve growth factor (NGF), the best characterized member of the family of neurotrophins. This study was designed to analyze the changes induced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to nerves and sensory corpuscles. Skin biopsy samples were obtained from 1) the hand and toes of normal subjects, 2) below the level of the lesion of patients with spinal cord injury affecting dorsal and lateral funiculi, 3) the cutaneous territory of entrapped peripheral nerves (median and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalin-fixed and paraffin-embedded, cut in serial sections, and processed for immunohistochemistry using antibodies against human p75 and TrkA proteins. The percentage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis. Spinal cord severance causes a decrease in p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands), both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory of entrapped nerves. Finally, in subjects with sectioned-grafted nerves, p75 IR was found close to controls in nerves, reduced in Meissner corpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA-like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups. Present results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of axonal continuity independently of possible restoration of axonal integrity due to grafts; 2) expression of TrkA-like IR in nerves and sensory corpuscles is sensitive only to nerve transection; 3) the corpuscular Schwann-related cells are the only cells involved in the above modifications, the perineurial cells remaining unchanged; 4) the expression of p75 and TrkA-like IR by Merkel cells is independent of normal innervation; 5) an adequate innervation of the skin seems to be necessary for the expression of p75 but not TrkA-like in nonneuronal cells, especially in the epidermis. A role for NGF in the maintenance of epidermis integrity is discussed.

Adult↗
PubMed2001

Results of surgical treatment of peripheral nerve injuries in upper extremities.

OUTLINE: This study presents the results of surgical treatment of nerves in upper extremities performed in our clinic over 15 years, from 1985 to 1999. Basic lines of surgical treatment of various injuries of nerves in upper extremities are presented and evaluated in the study. SYNOPSIS AND METHODS: 140 nerves in 123 patients were treated within this period. 95 reconstruction operations were performed by a microtechnique in 95 patients. All reconstruction surgeries were performed in cases characterized by complete and persisting neurological deficit and by the absence of action potentials in relevant nerves. In 42 patients, 45 nerves were reconstructed by an autotransplant. In 53 patients, reconstruction surgery was performed by suture of peripheral nerve that included treatment of 65 nerves. In this group, 10 patients were treated by suturation of 2 nerves and 3 nerves were suturated in one patient. In 28 patients, external neurolysis was the final surgical therapeutic treatment. In this group, neurolysis of 2 nerves was performed in 2 patients. The presence of action potential was always an important criterion in the determination of the type of surgical intervention. The analysis of the effectiveness of surgical intervention was performed with respect to: the period elapsed between injury and operation, age of the patient, character of injury, location of injury, category of injured nerve, type of surgical intervention. RESULTS: The best results were observed for external neurolysis and for n. medianus. Evaluation of the effectiveness of neural suture did not reveal any significant differences between neural grafts and classical suture. Similar results were obtained for surgical treatment of isolated nerve injuries and for cases involving the reconstruction of more than one nerve. Good or excellent results were typical for early treatment, for distal injuries and for clean incised wounds, especially in young patients. CONCLUSION: Early surgical revision combined with neurolysis and reconstruction surgery (if necessary) are crucial factors determining the outcome of operation in indicated cases. With respect to reconstruction operations we did not observe any significant difference between classical suture and suture using nerve graft.

Adult↗
PubMed2002

Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury.

Injured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration.

Animals↗
PubMed2007

Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury.

Peripheral nerve injury is often followed by the development of severe neuropathic pain. Nerve degeneration accompanied by inflammatory mediators is thought to play a role in generation of neuropathic pain. Neuronal cell death follows axonal degeneration, devastating a vast number of molecules in injured neurons and the neighboring cells. Because we have little understanding of the cellular and molecular mechanisms underlying neuronal cell death triggered by nerve injury, we conducted a proteomics study of rat 4th and 5th lumbar (L4 and L5) dorsal root ganglion (DRG) after L5 spinal nerve ligation. DRG proteins were displayed on two-dimensional gels and analyzed through quantitative densitometry, statistical validation of the quantitative data, and peptide mass fingerprinting for protein identification. Among approximately 1,300 protein spots detected on each gel, we discovered 67 proteins that were tightly regulated by nerve ligation. We find that the injury to primary sensory neurons turned on multiple cellular mechanisms critical for the structural and functional integrity of neurons and for the defense against oxidative damage. Our data indicate that the regulation of metabolic enzymes was carefully orchestrated to meet the altered energy requirement of the DRG cells. Our data also demonstrate that ligation of the L5 spinal nerve led to the upregulation in the L4 DRG of the proteins that are highly expressed in embryonic sensory neurons. To understand the molecular mechanisms underlying neuropathic pain, we need to comprehend such dynamic aspect of protein modulations that follow nerve injury.

Analysis of Variance↗
PubMed2006

Upper limb tremor induced by peripheral nerve injury.

We report a patient with proximal right upper limb tremor, secondary to direct peripheral nerve lesion caused by prior thoracic surgery. Electromyography demonstrated neurogenic abnormalities and tremor in muscles innervated by the thoracodorsal and long thoracic nerves. Somatosensory evoked potentials, transcranial magnetic stimulation, and MRI of the cervical and thoracic spine were normal. Tremor persisted in REM and non-REM sleep. These findings suggest a peripheral generator.

Arm↗
PubMed2001

Use of enhanced stimulation voltage to determine the severity of compressive peripheral nerve injury.

BACKGROUND: The aim of this study was to investigate whether enhanced stimulation voltage could be a predictor of the extent of injury in acute compressive peripheral nerve trauma. METHODS: The femoral nerves were exposed on both sides, in 11 anesthetized rabbits. Supramaximal stimulation voltage was used to produce a maximal-amplitude compound muscle action potential (CMAP) from the quadriceps femoris muscle. Afterward, the left femoral nerve was clipped for 1 minute, and the right femoral nerve for 5 minutes to produce an acute compressive injury. Immediately after removal of the clip, the proximal and distal sides of the clippage site were stimulated by gradually increased voltage until CMAPs were obtained. The same procedure was repeated at the 30th and 60th minutes. The ratio of the CMAP amplitudes obtained from proximal and distal stimulation was measured to establish a classification. RESULTS: The stimulation voltages and amplitudes of the CMAPs before clippage were similar with the after-clippage values obtained from distal stimulation (p > 0.05), but the after-clippage values obtained from proximal stimulation were different in both sides (p < 0.05). Doubled stimulation voltage was enough to obtain CMAPs on the left side, but eightfold the initial level was required on the right side. The amplitude ratios recovered to preinjury levels in all of the subjects on the left side, but only two showed recovery on the right side (p < 0.001). Histopathologically, there was axonal compression without discontinuity on the left side, whereas the fibers were dispersed on the right side. CONCLUSION: Stimulation voltage was found to discriminate the severity of the lesion in experimental peripheral nerve injury. Proximal to distal amplitude ratio seems to be a prognostic factor when the injury is less severe.

Action Potentials↗