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Rat-strain differences in recovery following peripheral-nerve allotransplantation.

The rat model is commonly utilized in peripheral nerve research. Due to the short length of the rat limb and the animal's inherent neuroregenerative capacity, the timing of assessment of nerve regeneration is critical, and significant differences between groups can be lost if assessment is done too late. Additionally, the comparison of data from different rat-strain combinations has been questioned. This study better defines the time course of recovery after peripheral nerve grafting, and examines differences between Buffalo (BUF), Lewis (LEW), and ACI rats. Tibial-nerve isografts and allografts were performed and harvested at 6, 8, 10, or 14 weeks. Histomorphometry documented a statistically significant difference in the ACI/LEW and LEW/LEW combination at 10 weeks. No strain differences in graft rejection were noted. The optimal time to assess for histomorphometric differences in the ACI/LEW and LEW/LEW combination is at 10 weeks postoperatively.

Animals↗

Cryo-immunogold ultrastructural localization of laminin in adult rat peripheral nerve.

Elucidation of the functional roles of the extracellular matrix component laminin in adult peripheral nerve has been hindered by differing accounts of its ultrastructural localization. This is the first report applying the advantages of the cryo-immunogold technique to laminin localization in peripheral nerve. Laminin labelling was found over the basal lamina and possibly over the immediately subjacent Schwann cell plasma membrane, but specific labelling appeared to be absent from other membranes (including those of non-myelinated axon/Schwann cell clusters) and from endoneurial collagen fibrils. It would appear that the functional roles played by laminin in normal adult peripheral nerve are likely to be mediated via its localization in the basal lamina, rather than through a more widespread distribution within the endoneurium.

Animals↗

Tapping with peripheral nerve block. a role for tactile feedback in the timing of movements.

This study examines the impact of peripheral nerve block, that is, the elimination of tactile feedback on synchronization performance. In a tapping experiment in which subjects were instructed to tap in synchrony with an auditory pacing signal, three different tasks were studied under conditions with and without peripheral nerve block: standard tapping with tactile contact, isometric tapping, and contact-free tapping. In addition, the maximum tapping rate was registered both with and without peripheral nerve block. It was found that the anticipatory error, usually observed in synchronization tasks, was affected by the peripheral nerve block in the standard tapping and the isometric tapping task. In both tasks, local anesthesia led to an increase in asynchrony between the pacing signal and the tap. Performance remained unimpaired in those tasks in which tactile information was assumed to play a minor role (maximum tapping rate and contact-free tapping). The results clearly demonstrate the importance of tactile feedback for the timing of movements. The predictions of a model assuming a strong correlation between the amount of sensory feedback and the size of the negative asynchrony in synchronization tasks were examined and discussed.

Adult↗

[Repair of peripheral nerve defect by xenogeneic acellular nerve basal lamina scaffolds].

OBJECTIVE: To explore the possibility to bridge peripheral nerve defects by xenogeneic acellular nerve basal lamina scaffolds. METHODS: Thirty SD rats were randomly divided into 5 groups; in each group, the left sciatic nerves were bridged respectively by predegenerated or fresh xenogeneic acellular nerve basal lamina scaffolds, autogenous nerve grafting, fresh xenogeneic nerve grafting or without bridging. Two kinds of acellular nerve basal lamina scaffolds, extracted by 3% Triton X-100 and 4% deoxycholate sodium from either fresh rabbit tibial nerves or predegenerated ones for 2 weeks, were transplanted to bridge 15 mm rat sciatic nerve gaps. Six months after the grafting, the recovery of function was evaluated by gait analysis, pinch test, morphological and morphometric analysis. RESULTS: The sciatic nerve function indexes (SFI) were -30.7% +/- 6.8% in rats treated with xenogeneic acellular nerve, -36.2% +/- 9.7% with xenogeneic predegenerated acellular nerve, and -33.9% +/- 11.3% with autograft respectively (P > 0.05). The number of regenerative myelinated axons, diameter of myelinated fibers and thickness of myelin sheath in acellular xenograft were satisfactory when compared with that in autograft. Regenerated microfascicles distributed in the center of degenerated and acellular nerve group. The regenerated nerve fibers had normal morphological and structural characters under transmission electron microscope. The number and diameter of myelinated fibers in degenerated accellular nerve group was similar to that of autograft group (P > 0.05). Whereas the thickness of myelin sheath in degenerated accellular nerve group was significantly less than that of autograft group (P < 0.05). CONCLUSION: The above results indicate that xenogeneic acellular nerve basal lamina scaffolds extracted by chemical procedure can be successfully used to repair nerve defects without any immunosuppressants.

Animals↗

Peripheral nerve surgery--retrospective and contemporary techniques.

The best technique for repairing peripheral nerves is the one that yields the best results with the greatest consistency. Because each repair has different anatomic and physical circumstances associated with it, the best approach is probably the one that best fulfills the needs of a given situation and this must be individualized from one situation to the next.

Age Factors↗

[Rehabilitation of war injuries of the upper extremities with peripheral nerve lesions at the and Praxis Clinic for physical medicine and rehabilitation in Sarajevo].

The war injuries are the most frequent multiple, with the difficult distructions of the tissue and the lesions of the peripheral nerves. By the injuries, the lesions of the nerv system represent the delicate problem for the physical medicine and the rehabilitation during the siege of Sarajevo (1992-1995), in the injuries with the lesions of the peripheral nerves, if they are not treated in the frame of the multiple las urgent, they are postponed the operative treatments longer than three months. This is from the aspect of the successfullness, prognostically and therapeutically, the limiting moment. The successfullness of the operative treatment of the lesions of the peripheral nerves significantly depends on that whether the operation was performed incide tree months. The more difficult consequences in these injuries can appear if simultaneously with the taking care of war injuries does not perform adequately surgical treatment adn the in time physical therapy trough the sufficient long time period. On the four year sample was analyzed the success fullness of the rehabilitation of the injuries of the upper extremities with the lesions of the peripheral nerves. Clinically, uniform, we valorized the success fullness of the treatment of all the patients by the marks from 0.5. In the complete sample the excellent success of the rehabilitation we confirmed in more than a half of patients. The better results show the group of the operated patients, in which is performed neuropathia or neurolisis. The capability of the regeneration of the injured peripheral nerves offers the real possibility for extraordinary recovery also in the most difficult injuries, then the preventions of the significant number of the consequences.

Arm↗

[Recent progress in diagnosis and treatment of the injury to the peripheral nerve].

OBJECTIVE: To investigate the latest development in diagnosis and treatment of the injury to the peripheral nerve. METHODS: The literature at home and abroad was reviewed, and the research findings with clinical experience in diagnosis and treatment for the injury to the peripheral nerve were summarized. RESULTS: The treatment for the total brachial plexus avulsion injury was successfully performed by the extra-plexus nerve transfer. The avulsion of the brachial plexus could be directly repaired by the healthy C7 nerve root transfer through the anterior spinal approach. The forearm flexors could be reinforced by the neurovascularized gracilis transplantation. MRI and CTM were the best methods of early diagnosis for the brachial plexus injury. The pure upper or lower root avulsion of the brachial plexus injuries could be repaired by the intra-plexus nerve transfer, which involved a transfer of part of the ulnar nerve in the arm to the motor nerve of the biceps for C5-C6 avulsion of the brachial plexus,and a transfer of selective fascicles of the healthy C7 nerve root or brachial muscle branch to the flexors muscle fascicles of the median nerve or anterior interosseous nerve. The thoracic outlet syndrome always occurred in this position when the neck muscle fatigue occurred in the typists or the game-players after their longstanding looking forwards. The C5 and C6 roots were rolled by the tendenofibrotic tissue at the origin of the scalenus. After a procaine block, the symptom subsided. Radiation neuropathy was a series of pathological changes caused by overdoses of the radiation therapy. The pathologic findings consisted of a series of vessel damages and final coagulation necrosis, which induced clusters of abnormally-dilated, thin-walled telangiectasias. Radiation neuropathy could be detected by MRI and could be differentiated from tumor. Once the diagnosis was established, the therapy should be begun early, including the systemic use of steroids, anticoagulation, and hyperbaric oxygen. CONCLUSION: Great progress has been made in diagnosis and treatment of the injury to the peripheral nerve, but a further study should be performed to promote regeneration of the nerves and reconstruction of the related functions.

Brachial Plexus↗

Peripheral nerve structures of experimental diabetes rats and the effect of insulin treatment.

The peripheral nerves of alloxan and streptozotocin diabetes rats six months after the induction of diabetes were morphologically investigated. The effect of insulin treatment was also examined. Prominent segmental demyelination and remyelination were observed in both alloxan and streptozotocin diabetes rats by isolated nerve fiber studies. Axonal degeneration and globular swelling were also recognized in some nerve fibers. Transmission electron microscopic findings were characterized by the figures of destructed myelin sheaths and axons. Reduplication and thickening of basal lamina of vasa nervorum were noted in the diabetes rats. Scanning electron microscopy revealed three dimensional architectures of degenerated nerve fibers and rough surface of Schwann cells in the diabetes rats. Insulin treated diabetes rats showed less structural changes of nerve fibers. It was indicated that the peripheral nerve lesions of experimental diabetes rats were caused by metabolic impairment of both axons and Schwann cells. Insulin treatment seemed to be effective on the experimental diabetic neuropathy.

Animals↗

Metabolic abnormalities in diabetic peripheral nerve: relation to impaired function.

An hypothesis is presented relating several well-defined metabolic abnormalities in diabetic peripheral nerve to impaired peripheral nerve function by a sodium-potassium ATPase mechanism. It is proposed that this hypothesis be tested in the most well-defined animal model for human insulin deficiency diabetes currently available--the BB diabetic rat.

Animals↗

Cellular and molecular correlates of the regeneration of adult mammalian CNS axons into peripheral nerve grafts.

Studies of the regeneration of CNS axons into peripheral nerve grafts have provided information crucial to our understanding of the regenerative potential of CNS neurons. Injured axons in the thalamus and corpus striatum produce regenerative sprouts within a few days of graft implantation, apparently in response to living cells in the grafts. The regenerating axons often grow directly towards the grafts, and enter Schwann cell columns where they elongate surrounded by Schwann cell processes. The regenerating CNS axons, and the Schwann cell processes along which they grow, initially express the cell adhesion molecules NCAM, and L1. The axons also express polysialic acid and, unlike regenerating peripheral axons, bind tenascin-C derived from Schwann cells. Wherever peripheral nerve grafts are implanted into the CNS they appear to promote the differential regeneration of CNS axons. Most of the axons which grow into grafts in the thalamus are derived from the thalamic reticular nucleus (TRN), whereas grafts in the striatum promote regeneration of axons from the substantia nigra pars compacta (SNpc) and grafts in the cerebellum promote regeneration from deep cerebellar nuclei (DCN) and brainstem precerebellar neurons. In contrast most thalamocortical projection neurons, striatal projection neurons and Purkinje cells in the cerebellar cortex are poor at regenerating. There are patterns to the expression of regeneration-related molecules by axons injured by nerve grafts in the CNS. Most neurons which regenerate well (e.g. TRN and DCN neurons) upregulate GAP-43, L1 and the transcription factor c-jun in response to a graft, whereas those neurons which do not regenerate well (e.g. Purkinje cells, thalamocortical and striatal projection neurons) do not upregulate these molecules. These observations suggest that some classes of CNS neurons may be intrinsically unable to regenerate axons and the repair of injuries in the brain and spinal cord may consequently require some form of gene therapy for axotomised neurons.

Animals↗

The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic changes.

This paper reviews light- and electron microscopic, histochemical and physiological evidence which demonstrate that peripheral nerve injury in mammals is followed by profound structural and functional changes in the central terminals of the affected primary sensory neurons. Available evidence indicates that at least some of these so-called transganglionic changes are the result of ganglion cell degeneration and death, although other mechanisms are probably in effect as well. Existing data suggest that this ganglion cell death does not effect all types of ganglion cells equally, but do not permit a clearcut answer to the question of which kinds of ganglion cells are affected more than others. Results from studies with microtubule inhibitors and antibodies to nerve growth factor are compatible with the notion that depletion of retrogradely transported trophic factors is involved in the production of certain transganglionic changes. This issue needs further examination, however. Physiological studies indicate marked alterations in certain primary afferent synaptic connections after peripheral nerve lesions. So far, these changes have not been satisfactorily correlated with the structural changes induced by similar lesions. Further studies on the structural and functional response of primary sensory neurons to peripheral nerve injury are likely to contribute to the understanding of the frequent failure to regain normal sensory functions after peripheral nerve lesions in man, as well as of the basic aspects of lesion-induced changes in general in the peripheral and central nervous system.

Acid Phosphatase↗

Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy.

Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt neurons to send out processes in peripheral nerves after axotomy are not well understood. Previously, we have shown oxidized galectin-1 (GAL-1/Ox) promotes initial axonal growth after axotomy in peripheral nerves. However, the mechanism by which GAL-1/Ox promotes axonal regeneration remains unclear and is the subject of the present study. To identify possible target cells of GAL-1/Ox, a fluorescently labeled recombinant human GAL-1/Ox (rhGAL-1/Ox) was incubated with DRG neurons, Schwann cells, and intraperitoneal macrophages from adult rats. Only the cell surfaces of intraperitoneal macrophages bound the rhGAL-1/Ox, suggesting that these cells possess a receptor for GAL-1/Ox. Experiments examining tyrosine phosphorylation revealed that rhGAL-1/Ox stimulated changes in signal transduction pathways in these macrophages. These changes caused macrophages to secrete an axonal growth-promoting factor. This was demonstrated when conditioned media of macrophages stimulated with rhGAL-1/Ox in 48 hr culture strongly enhanced axonal regeneration from transected-nerve sites of DRG explants. Furthermore, activated macrophage-conditioned media also improved Schwann cell migration from the transected-nerve sites. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced galectin-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. Oxidized galectin-1 then stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration.

Animals↗

[Effect of pre-degeneration of peripheral nerves on plasticity of cultivated Schwann cells and their cell number in vitro].

Predegeneration of peripheral nerve grafts is known to improve axonal regeneration in the sciatic nerve of the rat. Predegeneration involves sectioning the donor nerve in situ for a period of time prior to harvesting in order to allow Wallerian degeneration to take place. It is suggested that proliferating Schwann cells are responsible for this regeneration-promoting effect due to an increased production and accumulation of trophic factors. The aim of this study was to evaluate whether the proliferation of Schwann cells is increased after various predegeneration periods and whether predegeneration does affect the production of trophic factors. The rat's sciatic nerve was transsected distal to the spinal ganglion. Predegeneration was allowed to take place for one, two, three and four days and one, two and three weeks, respectively. The nerve was resected and prepared for Schwann cell cultivation. Cells cultivated from the contralateral untreated nerve served as control. S100 immunostaining, nerve-growth factor (NGF), and N-cadherin were used to characterize Schwann cells. Viability was assessed by fluoresceine fluorescence staining. Proliferation index was determined by BrdU DNA incorporation. Cultivation of cells harvested from predegenerated nerves indicated an increased proliferation of Schwann cells compared to the control. Proliferation effects depended on the period of predegeneration. A higher cell yield was obtained as early as 24 hours and up to three weeks after predegeneration. Optimal proliferation was seen after one week of predegeneration. The rapid expansion of Schwann cell populations oppressed the development of contaminating fibroblasts. NGF and N-cadherin were expressed by all S100-positive cells. Predegeneration did not affect viability. The determined high mitotic activity of predegenerated Schwann cells in combination with an early onset of proliferation may explain the regenerating-promoting effect of predegenerated nerve grafts. The expression of both NGF and N-cadherin in the predegenerated cultures indicates a high level of plasticity with dedifferentiation capacity, which in turn promotes neural regeneration. Predegeneration allows a proliferation of Schwann cells without concomitant pharmacological treatment. Thus, predegeneration of peripheral nerves is considered to be a highly efficacious method if a high yield of activated Schwann cells is desired within a short period of time. This may become relevant in the future of repair of peripheral nerve lesions, when autologous Schwann cells with their capacity to provide neurotrophines and cell adhesion molecules are used as cellular prostheses to bridge nerve gaps.

Animals↗

Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve.

The extracellular matrix glycoprotein, fibronectin, is a potent promoter of peripheral neurite outgrowth. Interactions of peripheral neurons with fibronectin have been shown to be primarily mediated by the beta 1 class of integrin heterodimers. In the present study, we have examined the expression and regulation of fibronectin and its integrin receptor, alpha 5 beta 1, in developing and regenerating chick peripheral nerve. We show that fibronectin and alpha 5 beta 1 are expressed at comparatively high levels in developing nerve with alpha 5 beta 1 expression on axons and non-neuronal cells. With nerve maturation, both proteins are less prominently expressed and the cellular pattern of alpha 5 beta 1 expression becomes more restricted. Following lesion of mature nerve, both fibronectin and alpha 5 beta 1 are strongly induced with prominent expression of alpha 5 beta 1 on regenerating neurites and Schwann cells. The elevation in fibronectin levels in the regenerating nerve is highest in the vicinity of the lesion, an area undergoing extensive cellular remodeling including Schwann cell migration and growth cone extension. Our results suggest that fibronectin and its receptor, alpha 5 beta 1, may mediate functionally important interactions in the development and regeneration of peripheral nerve.

Animals↗

Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis.

Although most randomized clinical trials conclude that the addition of continuous peripheral nerve blockade (CPNB) decreases postoperative pain and opioid-related side effects when compared with opioids, studies have included relatively small numbers of patients and the majority failed to show statistical significance during all time periods for reduced pain or side effects. We identified studies primarily by searching Ovid Medline (1966-May 21, 2004) for terms related to postoperative analgesia with CPNB and opioids. Each article from the final search was reviewed and data were extracted from tables, text, or extrapolated from figures as needed. Nineteen articles, enrolling 603 patients, met all inclusion criteria. Inclusion criteria were a clearly defined anesthetic technique (combined general/regional anesthesia, general anesthesia alone, peripheral nerve block), randomized trial, adult patient population (> or =18 yr old), CPNB (or analgesia) used postoperatively (intrapleural catheters were deemed not to be classified as a peripheral nerve catheter), and opioids administered for postoperative analgesia in groups not receiving peripheral nerve block. Perineural analgesia provided better postoperative analgesia compared with opioids (P < 0.001). This effect was seen for all time periods measured for both mean visual analog scale and maximum visual analog scale at 24 h (P < 0.001), 48 h (P < 0.001), and 72 h (mean visual analog scale only) (P < 0.001) postoperatively. Perineural catheters provided superior analgesia to opioids for all catheter locations and time periods (P < 0.05). Nausea/vomiting, sedation, and pruritus all occurred more commonly with opioid analgesia (P < 0.001). A reduction in opioid use was noted with perineural analgesia (P < 0.001). CPNB analgesia, regardless of catheter location, provided superior postoperative analgesia and fewer opioid-related side effects when compared with opioid analgesia.

Analgesics, Opioid↗

[Experimental study on functional rehabilitation of peripheral nerve with electric acupuncture].

OBJECTIVE: To observe the functional rehabilitation of injured peripheral nerve with electric acupuncture. METHODS: Sciatic nerve injury model was established by transection of left sciatic nerve in 60 Wistar rats, which were randomly divided into two groups. The experimental group was treated with electroacupuncture, no treatment in the control group. Change of nerve electrophysiological, power of muscle and sciatic functional index (SFI) were observed. RESULTS: Nerve muscle-action potential (MAP) and motor nerve conduction velocity (MNCV) in the experimental group were better than that of the control group (P < 0.01). The single muscle twitch and tetanization of gastrocnemius muscle were higher in the experimental group too (P < 0.05). SFI were significantly higher in the experimental group (P < 0.05). CONCLUSION: Electric acupuncture therapy can improve functional rehabilitation of injured peripheral nerve.

Acupuncture Therapy↗