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Clustering of slowly adapting type II mechanoreceptors in human peripheral nerve and skin.

The intrafascicular organization of human peripheral nerves was studied with percutaneous microneurography in the median, radial and peroneal nerves with one-surface or two-surface thin diameter concentric needle electrodes. Data from 33 recording sites containing 47 slowly adapting type II (SAII) units were analysed. At many sites two, sometimes even three, neighbouring SAII units were recorded from the explored nerve fascicle and they had adjacent or even overlapping cutaneous receptive fields. Among pairs of SAII units found at the same site, one unit often had ongoing discharge, whereas the other was silent under resting conditions. The neighbouring SAII units were optimally activated by stretching the skin in different directions. Stretching the same skin area in different directions produced different unit recruitment. Clustered SAII units were often found in sites where Pacinian afferents and skin sympathetic activity were also recorded. No significant difference was observed in the degree of grouping of SAII units either between recordings obtained with one-surface versus two-surface electrodes or between glabrous and hairy skin. The data do not support the notion that myelinated fibres are randomly organized in peripheral nerve fascicles. Instead, the findings suggest that SAII units tend to be clustered in human peripheral nerves. Furthermore, the response of groups of SAII units to skin stretch suggests that they play a role in proprioception. Dual channel recordings with two-surface concentric needle electrodes may provide a novel approach to study fibre organization in human peripheral nerves and the behaviour of groups of nerve fibres.

Adaptation, Physiological↗

CNS axonal regeneration with peripheral nerve grafts cryopreserved by vitrification: cytological and functional aspects.

To test cool-warm protocols for storing peripheral nerves, 4-cm-long-nerve segments were removed from the hindleg of adult rats and cryopreserved using a vitrification solution (or cryoprotective mixture) containing a mixture of polyalcohols (2,3-butanediol, 1,2-propanediol, polyethylene glycol, and Belzer U.W. medium). Schwann cell viability and morphology were studied with regard to the effect of (i) cryoprotective mixture concentration (100, 50, and 30% diluted in human serum albumin at 4%), (ii) duration of exposure (10, 15, or 30 min in a single step) of nerves to the cryoprotective mixture, (iii) cooling rate (F1/F2, F3, and F4: 3, 12, and 231 degrees C/min, respectively), and (iv) type of replacement of cryoprotectant (T1, one step; or T2, perfusion) after warming. Nerves exposed 10 min to cryoprotective mixture 50% (2,3-butanediol, 1.926 mol.liter-1; 1,2-propanediol, 3.063 mol.liter-1; polyethylene glycol, 0.084 mol.liter-1; and Belzer U.W., 22.4 mosm-1) and cooled-warmed with the F2/F3/F4-T2 protocols contained live and correctly cryopreserved Schwann cells. The capacity of these cryopreserved nerve segments (n = 6) to be subsequently repopulated by regenerating axons from central neurons was compared to that of fresh nerves when used as peripheral nerve autografts implanted within the spinal cord at the level of the descending respiratory pathways. All cryopreserved nerve grafts were successfully reinnervated by regenerated central axons. Unitary spontaneous action potentials propagated along these axons were assessed by recording the discharge of tested nervous filaments (T) from the grafts in artificially ventilated and paralyzed animals. Out of 535 T, 32 (6 +/- 1.2%) presented spontaneous unitary activity with respiratory (R, n = 2) and nonrespiratory (NR, n = 30) pattern of discharge. The T mean number, the occurrence rate referenced to the total number of T (R/T, NR/T, and R + NR/T) and the mean number of spontaneous units (R, NR, R + NR) were compared to those of fresh spinal peripheral nerve grafts. Except for T, cryopreserved peripheral nerve grafts contained statistically significantly (P < 0.05) less spontaneous R and NR unitary activity, which represented, respectively, 6.2 +/- 6.2 and 26.8 +/- 5.7% of that found in the control group. These data indicate that nerves cryopreserved with the protocols described above contain viable Schwann cells which constitute a suitable support to induce regeneration of central fibers. The effectiveness of nerve cryopreservation by vitrification is discussed with regard to Schwann cell viability following cool-warm protocols and to subsequent reinnervation of the cryopreserved peripheral nerve grafts.

Animals↗

Point mutation of neu oncogene in animal peripheral nerve sheath tumors.

Thirty-four peripheral nerve sheath tumors of four domesticated animal species were characterized and assayed for point mutation of the neu oncogene. Based on their morphoimmunophenotype, 32 tumors were classified as schwannomas. Schwannoma morphology was characterized by the presence of Antoni type A and B pattern and immunoreactivity for S-100 protein and vimentin. Two anaplastic and metastatic tumors originating from spinal cord root, immunonegative for S-100 protein and positive for vimentin, were classified as malignant peripheral nerve sheath tumors (MPNSTs). Four malignant schwannomas and two MPNSTs expressed a point mutation of the neu oncogene by the polymerase chain reaction-restriction fragment length polymorphism method. The finding of neu oncogene mutation could be a useful diagnostic genetic marker in the malignant form of peripheral nerve sheath tumors in animals.

Animal Diseases↗

Tension and creep phenomena in peripheral nerve.

Tension introduced into peripheral nerves during their surgical repair may reduce the success of this procedure. Two mechanical factors are important; the tension required to effect a repair, and the rate at which this tension changes after surgery. These two factors have been investigated in the rat sciatic nerve. The results show an increasing resistance to elongation of the nerves with increasing tension. Under a constant elongation the tension in the nerves reduces by about 30 per cent in the first 10 minutes and by a small amount in the following 20 minutes.

Animals↗

Thermographic presentation of cutaneous sensory and vasomotor activity in the injured peripheral nerve.

Impaired function of cutaneous segments of monkey peripheral nerves experimentally blocked by lidocaine anesthesia was clearly visualized by means of elevated temperature measurements obtained on computerized color telethermography. Mean temperature elevations in the segments of anesthetized primate nerves were 2.40 degrees C at the ulnar segment 17 minutes after nerve block, and 1.20 degrees C at the peroneal nerve at 20 minutes. The vasomotor activity of specific nerves, recorded after local anesthesia and displayed by color telethermographic imaging, corresponded to the distribution of sensory segments identified by more cumbersome means. Telethermography is therefore shown to be a useful tool, both qualitatively and quantitatively, in mapping cutaneous distribution of peripheral nerves and for evaluation of peripheral nerve injuries.

Animals↗

Progress in peripheral nerve reconstruction.

The development of peripheral nerve surgery over the past 15 years has been fascinating to watch. Significant improvements have been achieved by the wide application of techniques which were developed before this period. New approaches may revolutionize the tactics of nerve repair in the near future.

Humans↗

Nerve suture without tension, a method for repairing transected peripheral nerves.

An analysis of primary epineural end to end sutures of transsected peripheral nerves, operated upon before 1970, showed good motor and sensory function in only 60%. With the new perineural suturing technique without tension and if necessary by using autologous nerves for bridging large nerve defects the good results raised to 87%.

Humans↗

Occurrence of an insulin-like peptide in extracts of peripheral nerves of th cat and in extracts of human vagal nerves.

Biopsies from various peripheral nerves were collected from living cats. The biopsies were extracted with acid ethanol and the insulin-like immunoreactivity (ILI) content of the extracts determined with radioimmunoassay. The vagal, sciatic and radial nerves contained on the average 90, 3 and 28 ng of ILI per gram nerve tissue (wet weight), respectively. In the sympathetic trunc no ILI was found. In order to partly purify and characterize the nerve ILI extracts these were run on an HPLC system. the ILI coeluted with standard bovine insulin. The same amounts of ILI were found in the nerve extracts whether run on the HPLC system or not. It can be concluded that all of the immunoreactive material of the nerve extracts corresponds to insulin or to a peptide very similar to insulin. In two cats the radial and sciatic nerves were ligated for 24 h. Two to ten times more ILI occurred in biopsies taken proximal to the site of ligation than in those from corresponding distal biopsies, indicating that the insulin-like material is transported distally within the nerves. ILI was found in extracts from vagal nerves taken from 3 days old human autopsy material. Also this human ILI coeluted with the bovine insulin standard in the HPLC system.

Animals↗

[Effects of ischemia on peripheral nerve evoked potential. Experimental and clinical study].

The association between impaired circulation and peripheral nerve disorders has been recognized for many years. Although many experimental and clinical studies have been carried out on the "ischemic neuropathy", the routine examination to certify it may have not yet been established. Peripheral nerve evoked potential measurement has been used to evaluate the function of the peripheral nerve directly. Some electrophysiological findings concerning nerve ischemia were reported. Most authors reported decreased amplitude, slowed conduction rate, and increased refractory period. But a transient increase in amplitude during ischemia is a characteristic phenomenon in the peripheral nerve as well as in spinal cord evoked potential, as reported by the author previously. Since the purpose ot this study was whether this phenomenon could be a indicator of some kind of pathological condition of the peripheral nerve, experimental and clinical studies were designed to obtain the conditions required for the observation of this phenomenon and to establish a practical method for the differentiation of ischemic neuropathy from other ones. Twenty cats were used in the experimental study. The blood supply to the nerve was controlled by tightening a noose around the base of the ascending aorta. In the clinical studies, sixteen healthy subjects 11 diabetics, 3 patients with arteriosclerosis obliterans, and 3 patients with malignant RA were examined. Since a transient reduction in threshold was observed during ischemia simultaneously with a transient augmentation in amplitude, the latter was assumed to be due to the former. In the animal experiment, the amplitude did not increase further even during complete obstruction of the ascending aorta following a 10-minute partial obstruction of the blood supply. In the clinical studies, the augmentation of amplitude during ischemia was statistically higher in healthy persons than in the patients mentioned above. The requisites for observing the transient augmentation in amplitude were: (1) complete ischemia of the peripheral nerve; optimally ten minutes of ischemia, (2) submaximal stimulation; optimally the strength of stimulation with which the amplitude of the evoked potential became 1/3 of the maximum and (3) maintenance of the blood supply to the peripheral nerve before ischemia. The nerve should not be ischemic before complete ischemia or application of the tourniquet.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

An experimental model of peripheral nerve adhesion in rabbits.

We studied the effects of peripheral nerve adhesion in a rabbit sciatic nerve model. After nerve exposure, its adventitial layer was sutured with 8-0 nylon to the nerve bed, which had been cauterised to promote adhesion. Nerve kinematics, electrophysiology, blood flow and histology were assessed. Rabbits in which Fontana's bands were visible as normal through the epineurium, classified as a nonadhesion group (group I), lacked intraneural fibrosis. In this group, nerve conduction and nerve blood flow were well maintained. Rabbits in which Fontana's bands could not be seen were classified as the adhesion group (group II). This group was classified into two levels pathologically; thickening of epineurium and perineurium was observed but no endoneurial fibrosis (group IIa), and endoneurial fibrosis (Wallerian degeneration, myelin sheath thinning and fibrosis between nerve fibers) was noted (group IIb). Compound muscle action potentials (CMAP) were reduced in amplitude and blood flow was significantly decreased at adhesion sites in group IIb. In conclusion, adhesion of peripheral nerve to surrounding tissues results in fibrosis in the nerve that contributes to peripheral nerve dysfunction.

Action Potentials↗

[Experimental study on tension and stretching to peripheral nerve].

As to the suturing large peripheral nerve defects under tension, several questions have not yet been answered. How long is the critical gap for functional recovery, and how can these gaps be overcome? In order to resolve these questions, an experimental study was undertaken using sciatic nerves of the 83 mongrel adult dogs. A Two Stage Procedure for the neurorrhaphy was invented to overcome the large nerve defect. This method consists of the following two stages. The first stage operation is done by gradual approximation of both stumps against tension with a single and thick suture material. The second stage operation is done three weeks following the first stage operation, consisting of epineural suture under the microscope after refreshment of both stumps. The longest nerve defect in which axonal regeneration was accomplished by this Two Stage Procedure ranged 5 cm (proximal: 5.2% elongation, distal: 12% elongation) in the sciatic nerve of dogs.

Animals↗

Peripheral nerve injuries in children.

Recovery after peripheral nerve injuries in children is more complete than in adults and is inversely related to the age of the patient. The prognosis for the return of sensation following laceration of the median, ulnar, or digital nerve depends upon recovery of two point discrimination (in millimeters approximately equal to the child's age) at the time of nerve repair. The better results in children probably reflect the greater adaptability of the immature central nervous system to the nerve injury. Operative exploration of an open wound when there is a potential for nerve injury in an uncooperative child is the only sure way of determining the status of the nerves. Primary repair of cleanly divided nerves in tidy wounds is advocated if it can be done competently. Secondary repair is indicated for avulsion injuries, gunshot wounds, crush injuries, and human or animal bites. Delicate, atraumatic technique and accurate repair of the divided nerve are stressed. The more exacting technique of funicular repair may yield better results. Interfascicular cable grafting is a new and useful alternative to extensive mobilization in closing nerve gaps. Nonoperative treatment of nerve injuries associated with closed fractures is advocated unless there are no signs of nerve regeneration in two to three months. Obstetrical brachial plexus injuries of the upper plexus carry a better prognosis than lower plexus or total plexus injury. Early range of motion exercises to prevent contractures are stressed. Maximal recovery takes place within two years. The acute nerve compression syndrome should be considered an emergency and may require surgical decompression if it is severe and if rapid return of function does not occur following reduction of the fracture.

Adolescent↗

On sampling and sampling errors in histomorphometry of peripheral nerve fibers.

Histomorphometrical assessment of regenerated peripheral nerves is a very common goal of many studies in experimental microsurgery. In this paper, the main critical issues in nerve fiber sampling for quantitative morphological assessment are addressed. The equal opportunity rule, i.e., the basic paradigm of random sampling, is described, together with an explanation of how sampling errors, in the selection of histologic fields and of the nerve fibers inside them, can produce a bias in quantitative estimates. Finally, some practical suggestions on how to cope with the most common sampling errors are provided, in order to help researchers obtain reliable histomorphometrical data on peripheral nerve fibers.

Humans↗

The structure and composition of peripheral nerves and nerve roots in the Sprawling mouse.

Peripheral nerves and lumbar nerve roots of Sprawling, a neurological mutant mouse, were examined with light and electron microscopy. The peripheral nerves and the dorsal roots were thin and grey and were composed predominantly of small myelinated and unmyelinated axons. No evidence of axonal or myelin degeneration was found. Quantitative studies showed a marked reduction in the total number of myelinated axons with preponderance of those of 2-5 micron in diameter or less, most marked in the dorsal roots in which there was also an increase in the proportion of axons which were unmyelinated. In the ventral roots there was a deficiency in the contribution formed by myelinated axons of small calibre, probably indicating a deficiency of gamma fibres. Examination of the myelinated axons in nerves and roots showed a normal relationship between fibre size and internodal lengths and number of myelin lamellae. The findings suggest that the genetic defect in Sprawling is responsible for a failure of myelination of sensory axons. The deficiency of large sensory axons and of small motor axons can be correlated with the deficiency of muscle spindles.

Animals↗

Subclinical peripheral nerve involvement in patients with rheumatoid arthritis.

OBJECTIVE: Clinical involvement of the peripheral nervous system is uncommon in rheumatoid arthritis (RA); the most common disorders are multiple mononeuritis, sensorimotor neuropathy, and entrapment neuropathy. This study was undertaken to investigate the occurrence of electrophysiologically evident peripheral nerve involvement in RA patients without a clinical history of peripheral nerve involvement. METHODS: Forty RA patients were examined neurologically and electrophysiologically, and sural nerve biopsies were performed in 4. RESULTS: No patient reported symptoms or signs of peripheral nerve involvement. Twenty-six patients (65%) exhibited electrophysiologic findings consistent with a sensorimotor neuropathy (in 2 of them a carpal tunnel syndrome was also present), while 3 patients showed isolated carpal tunnel syndrome. There was a moderate loss of myelinated fibers in 3 of the 4 nerve biopsy samples, and all showed an increased number of endo- and perineurial vessels and some signs of axonal degeneration. CONCLUSION: Patients with RA may have electrophysiologic and histologic findings of peripheral nerve damage, even in the absence of clinical evidence of peripheral nerve involvement.

Adult↗

Development of neuropathic pain in the rat spared nerve injury model is not prevented by a peripheral nerve block.

BACKGROUND: The mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. One hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. The aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model. METHODS: Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. After sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. Development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n = 12) and in controls (n = 11). RESULTS: Bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. Once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups. CONCLUSIONS: Peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. It is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.

Animals↗

Expression of cholinesterase in the Schwann cells of peripheral nerves during development.

In peripheral nerves of mouse embryos Schwann cells exhibit a high activity of unspecific cholinesterase. At first (day 12 of embryonic development) this enzyme occurs in the nuclear envelope and in the granular endoplasmic reticulum. Thus, it is possible to differentiate between Schwann cells and fibroblasts which lack cholinesterase. Later on (day 16) the cholinesterase has shifted to the cell membrane of the Schwann cells. However, only that part of the plasmalemma which encircles single axons and the mesaxons exhibits an irregular deposition of the reaction end product. In newborns the first loops of the just formed myelin sheath are still stained. With maturation of the myelin sheath the enzyme activity disappears. The functional role of cholinesterase is unclear. Possible roles are discussed. The expression of cholinesterase in Schwann cells depends on the integrity of the axons. After a few hours, the cultivation of amputated limbs results in a reduction of the enzyme activity. After 1 day in culture cholinesterase disappears totally.

Animals↗

AChE-positive fiber growth after hippocampal fimbria transection and peripheral nerve homogenate implantation.

Gelfoam treated with peripheral nerve homogenate was implanted into a site of hippocampal fimbria transection in the adult rat to assess whether the homogenate might enhance growth of AChE-positive fibers into the lesion site and whether the fiber growth might be directed to the implants. Homogenate was prepared from intact peripheral nerve and in a few cases from degenerated nerve. Some implants were encased in Silastic. Homogenate was also injected into the denervated hippocampus. The major finding was that AChE-positive fiber growth was associated with regions of high astroglial cell content in preference to the relatively hypocellular implants. No clear differences in AChE fiber sprouting into the lesion site, fiber growth into implants, or hippocampal reinnervation were noted between homogenate and saline-treated animals.

Acetylcholinesterase↗