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[Morphometric rationale for utilization of peripheral nerves of the human fetus as vascularized allografts].

The authors performed morphometric section studies of the peripheral nerves of 25 human fetuses of 17-26 week development. The purpose of the study was determination of the technical possibility of using revascularized nerves of the human fetus as grafts for replacement of post-traumatic defects in the peripheral nerves. The peripheral nerves of the upper limbs of fetuses of the indicated developmental periods were found to be formed morphologically. The results of morphometric study showed that it is technically possible to obtain the median, ulnar, and radial nerves on a vascular pedicle. The length and diameter of the vessels of the vascular pedicle of the upper limb peripheral nerves allow revascularization of the brephograft to be accomplished by means of microsurgical techniques.

Fetal Tissue Transplantation↗

Influence of peripheral nerve grafts on the expression of GAP-43 in regenerating retinal ganglion cells in adult hamsters.

We have examined the ability of axotomized retinal ganglion cells in adult hamsters, to regenerate axons into a peripheral nerve graft attached to the optic nerve and the expression of GAP-43 by these neurons. We also examined the effect on these events of transplanting a segment of peripheral nerve to the vitreous body. The left optic nerves in three groups of hamsters were replaced with a long segment of peripheral nerve attached to the proximal stump of the optic nerve approximately 2 mm from the optic disc to induce regeneration of retinal ganglion cells into the peripheral nerve. An additional segment of peripheral nerve was transplanted into the vitreous of the left eye in the second group. The animals from the first and second groups were allowed to survive for 1-8 weeks and the number of regenerating retinal ganglion cells was determined by applying the retrograde tracer, Fluoro-Gold to the peripheral nerve graft and the expression of GAP-43 was studied by immunocytochemistry in the same retinas. As a control, a segment of optic nerve was transplanted into the vitreous body of the left eye in the third group of hamsters. These animals were allowed to survive for 4 weeks and the number of regenerating retinal ganglion cells was counted as in Groups 1 and 2. The percentages of the regenerating retinal ganglion cells which also expressed GAP-43 were very high at all time points in Group 1 (with no intravitreal peripheral nerve) and Group 2 (with intravitreal peripheral nerve) and at 4 weeks for the Group 3 (with intravitreal optic nerve) animals. In addition, the number of regenerating retinal ganglion cells, the number of retinal ganglion cells expressing GAP-43 and the number of regenerating retinal ganglion cells which also expressed GAP-43 were much higher in Group 2 than in Group 1 at all the time points and it was also much higher in Group 2 than in Group 3 at 4 weeks whereas there was no significant difference between the results from Groups 1 and 3 at 4 weeks. These data suggested that there was a close correlation between the number of the axotomized retinal ganglion cells regenerating axons into the peripheral nerve graft attached to the optic nerve and the expression of GAP-43.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Characterization of the calcium-induced disruption of neurofilaments in rat peripheral nerve.

Transverse frozen sections of desheathed rat peripheral nerve were incubated in media of different composition prior to fixation and processing for electron microscopic examination. Neurofilaments remained intact when these tissues were incubated in calcium-free media. A loss of neurofilaments and their replacement by granular debris occurred in myelinated and unmyelinated fibers following incubation in media containing 2 mM calcium. The calcium-mediated disruption of neurofilaments was inhibited by preincubation or incubation with 1 mM p-chloromercuribenzoate (PCMB). The inhibition by preincubation with PCMB could be partially reversed by subsequent preincubation with 10 mM dithioerythritol (DTE). Calcium-mediated breakdown of neurofilaments did not occur after prolonged preincubation in calcium-free media, a finding which suggested that neurofilament disruption was dependent upon a tissue factor which could be lost or inactivated in frozen-sectioned nerve tissues. The findings of the present study provide morphological evidence that neurofilament disruption in mammalian peripheral nerve is mediated by a calcium-activated, PCMB-sensitive enzyme in the axoplasm of myelinated and unmyelinated nerve fibers.

Animals↗

The acute effect of peripheral nerve transection on digital thermoregulatory function.

PURPOSE: This study tests the hypothesis that major peripheral nerves serve as important routes for adrenergic neural fibers and therefore peripheral nerve injury affects cutaneous perfusion within the nerve's sensory innervation territory. The specific aim of the study was to determine whether an acute isolated peripheral nerve injury would result in alteration of blood flow to a specific digit, digital pain, and/or cold sensitivity. METHODS: The influence of peripheral nerves on their dominant area of autonomic vasomotor function was evaluated in 9 patients who had primary neurorrhaphy after a single complete median or ulnar nerve transection. At a mean follow-up of 47 days the response of digital perfusion to a cold stress was examined in these patients by using isolated cold stress testing and laser Doppler fluxmetry. Patients also completed subjective questionnaires to evaluate their symptoms. RESULTS: The affected hands showed a decreased cutaneous perfusion when compared with the contralateral hands during all 3 phases of the cold stress test. In addition cutaneous perfusion patterns evaluated by laser Doppler perfusion imaging showed markedly decreased cutaneous perfusion patterns in the digits within the innervation territory of the injured nerve. There was no notable difference in digital baseline temperatures and temperature changes after an isolated cold stress test between the most affected digits of the injured hands and corresponding digits of the unaffected, contralateral hands. All 9 patients reported mild to severe digital numbness, 8 reported mild to severe pain, and 4 reported mild to moderate cold sensitivity of the upper extremity. CONCLUSIONS: This study documents that cutaneous perfusion and thermoregulatory function is altered after isolated peripheral nerve injury.

Adult↗

Infection of distal peripheral nerves by M. leprae in infected armadillos; an experimental model of nerve involvement in leprosy.

Mechanisms of localization of Mycobacterium leprae to the peripheral nerves and of subsequent nerve injury are not understood. No experimental animal model has been available for use in examining the pathogenesis of M. leprae-induced nerve injury. A detailed dissection was, therefore, done of the major peripheral nerves in the extremities of six M. leprae-inoculated armadillos, three of which had developed characteristic disseminated infection. All of the animals with disseminated infection had extensive involvement of the peripheral nerves, increasing in intensity as the nerve was followed distally. No M. leprae were found in the animals without disseminated infection. The degree of infection was greater in epineural tissues than in the intraneural compartment (i.e., Schwann cells) at all levels. The infection of nerves by M. leprae was associated with focal interstitial, mononuclear cell infiltration of involved nerves. These results suggest that: 1) armadillos offer a model for the study of neural involvement in leprosy, since the pattern of neural distribution in susceptible armadillos is comparable to the pattern of nerve involvement in man; 2) early localization of M. leprae may be to the epineural tissues, including lymphatic and vascular structures and extracellular matrix; 3) Schwann cell involvement may be a late event; and 4) mechanisms involving the endothelium of epineural and perineural tissues may be important in the selective localization of M. leprae to peripheral nerves.

Animals↗

The ultrastructure of bovine peripheral nerve sheath tumours.

Bovine peripheral nerve sheath tumours from 30 cattle were similar ultrastructurally to human schwannomas and neurofibromas. Bovine neurofibromatous tissue had large amounts of extracellular material, primarily collagen and electron lucent granular material. The principal cells had basal laminae and a disorganized proliferation of the plasmalemma. Axons were consistently seen and were surrounded by the plasmalemma of principal cells. The principal cells seemed to be Schwann cells or variants of them. Bovine schwannomas had areas similar to Antoni type A tissue with sparse extracellular material, few, if any, axons, and an apparent organized layering of cytoplasmic processes clad in a basal lamina. Cell nuclei often formed palisades. The principal cells in bovine schwannomas might be derived either from Schwann cells or perinuerial cells. Bovine schwannomas appeared together with bovine neurofibromatous tissue in affected nerves.

Animals↗

Technical and interpretive problems of peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit.

OBJECTIVE: To review the literature and provide an overview of the technical and interpretive problems associated with peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit. DATA SOURCES: A computerized search on MEDLINE from 1985 through 1994 was performed to identify English-language comparative studies, abstracts, and review articles pertaining to peripheral nerve stimulation, train-of-four monitoring, and neuromuscular blockade in the critical care setting. STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans were selected and information was extracted on the use of peripheral nerve monitoring in the critically ill. DATA SYNTHESIS: Use of peripheral nerve stimulation is complicated in the intensive care unit. Problems may occur with the patient, the device, as well as operator technique, all of which may lead to errors in interpretation of the depth of paralysis. The critically ill patient has changing comorbid disease states and total body water composition, which may impair the accuracy or reproducibility of measurements. Technical problems relate to the operation of the device, electrode placement, and suboptimal delivery of the desired current. Difficulties in performing peripheral nerve stimulation and interassessor variability contribute to errors of interpretation. CONCLUSIONS: These difficulties compromise the precision, accuracy, and reliability of the peripheral nerve stimulator as a tool for monitoring neuromuscular blockade in the critically ill. Peripheral nerve stimulation should be used in conjunction with clinical parameters to make decisions regarding dose adjustments. Doses should be reduced as much as possible to provide the minimum depth of paralysis that is clinically appropriate. Technical directions and training programs for peripheral nerve stimulation should be developed, and designated individuals should be trained in its application. Large, prospective, controlled studies are necessary to evaluate the incidence of prolonged paralysis or motor neuropathy with administration of neuromuscular blocking agents in patients whose dose is adjusted on the basis of peripheral nerve stimulation.

Critical Care↗

Regulation of immediate-early gene expression in rat retinal ganglion cells after axotomy and during regeneration through a peripheral nerve graft.

To determine mechanisms of structural plasticity in adult CNS neurons, we investigated the expression of immediate early genes (IEGs) in the rat retina. Gene products of different IEG families (JUN and FOS proteins) and cAMP-responsive element binding protein (CREBP) were examined by immunohistochemistry under three different paradigms. Normal rats which were not axotomized were compared with axotomized animals, were retinal ganglion cells (RGCs) were axotomized by intraorbital optic nerve cut and retrogradely labeled with fluorogold (FG). Under these circumstances, RGCs show only transient sprouting, followed by continuous retrograde RGC degeneration. In the third group, after the optic nerve lesion, adult rats additionally received a sciatic nerve graft to the transected optic nerve stump. This allows some RGCs to regenerate an axon into the grafted nerve. In both groups, the time course of RGC survival and JUN, CREB, and FOS protein expression was monitored. In normal animals, JUN-Immunoreactivity (JUN-Ir) was not detectable in the retinal ganglion cell layer. JUN-Ir was induced in about 70% of all FG-positive RGCs 5 days after axotomy. The expression of JUN-Ir stated to decline 8 days after axotomy. Only a few JUN-Ir-positive RGCs were found after 2 weeks. In transplanted animals, however, the numbers of JUN-Ir-positive RGCs were significantly higher 2 and 3 weeks after transplantation compared to animals that exclusively received axotomy. Furthermore, in grafted rats, about 70% of the regenerating RGCs expressed JUN-Ir 2 weeks after grafting as compared to only 38% JUN-positive RGCs among the surviving but not regenerating RGCs. In normal animals CREBP-Ir was constitutively expressed in nearly all cells of the retinal ganglion cell layer. The decline in number of CREBP-Ir-positive cells paralleled the axotomy-induced RGC death. FOS-Ir-positive cells were not found in the ganglion cell layer at any time. These results demonstrate a selective and transient JUN expression of RGCs after axotomy which is sustained during axonal regeneration. This suggests that sciatic nerve grafts are able to regulate the expression of JUN proteins in axotomized RGCs of adult rats.

Activating Transcription Factor 2↗

Nonselective nerve fibre damage in peripheral nerves after experimental thermocoagulation.

In this study the morphological effects of local heat application by controlled thermocoagulation to the sciatic nerve of rabbits are investigated. It concentrates on the question of a possible selective elimination of nerve fibres depending on their calibers. Temperatures of 50 degrees C, 55 degrees C, 60 degrees C, 70 degrees C and 90 degrees C were applied for 45 seconds. The nerves were examined histologically after 2-3 minutes, 7 and 12 days and 5 weeks. The light and electronmicrographs show no differential vulnerability of small myelinated or unmyelinated fibres as proposed by Sweet and Wepsic [20]. At a temperature of 50 degrees C no fibre is damaged whereas at 60 degrees C the fibre damage extends over nearly the total cut surface of the nerve. Even at the critical temperature of 55 degrees C affecting only part of the cross-section no predilection of any fibre caliber was observed. In summary thermocoagulation seems not to be able to cause selective fibre damage.

Animals↗

The musculocutaneous nerve: ultrasound appearance for peripheral nerve block.

BACKGROUND AND OBJECTIVES: To gain complete anesthesia of the forearm, block of the musculocutaneous nerve is necessary. Variations in its course and position make localization of the musculocutaneous nerve problematic. The aim of the study is to describe the ultrasound appearance of the musculocutaneous nerve in the axilla and to suggest potential areas to target neural block. METHODS: We scanned the axillary regions of 19 volunteers and assessed the size and shape of 34 musculocutaneous nerves at entry into, exit from, and in the center of the coracobrachialis muscle. Furthermore, we measured the depth of the musculocutaneous nerve under the skin surface and its distance from the axillary artery at those 3 measurement points. RESULTS: As it travels through the coracobrachialis muscle, the musculocutaneous nerve changes in shape from oval to flat-oval to triangular. During this course, the musculocutaneous nerve also separates from the axillary artery and becomes more lateral while changing its depth from the surface. The musculocutaneous nerve increases its transverse area along this nerve path. In 2 subjects, the musculocutaneous nerve could not be visualized unilaterally within the course of the coracobrachialis muscle. CONCLUSIONS: Knowledge of its ultrasound appearance facilitates localization and successful block of the musculocutaneous nerve. Because the distance between the musculocutaneous nerve and brachial plexus varies, different locations of musculocutaneous nerve puncture during ultrasound-guided regional anesthesia can be chosen.

Axillary Artery↗

Development of a malignant peripheral nerve sheath tumor following treatment for testicular seminoma.

A novel case is reported in which an S2 nerve root malignant peripheral nerve sheath tumor was diagnosed approximately 8 years after treatment for Stage I testicular seminoma. This patient underwent right orchiectomy and subsequent irradiation therapy to the periaortic region, including the sacrum. Postoperative radiation therapy likely played a role in the development of this second malignancy.

Adult↗

Optic nerve regeneration after intravitreal peripheral nerve implants: trajectories of axons regrowing through the optic chiasm into the optic tracts.

We have studied axon regeneration through the optic chiasm of adult rats 30 days after prechiasmatic intracranial optic nerve crush and serial intravitreal sciatic nerve grafting on day 0 and 14 post-lesion. The experiments comprised three groups of treated rats and three groups of controls. All treated animals received intravitreal grafts either into the left eye after both left sided (unilateral) and bilateral optic nerve transection, or into both eyes after bilateral optic nerve transection. Control eyes were all sham grafted on day 0 and 14 post-lesion, and the optic nerves either unlesioned, or crushed unilaterally or bilaterally. No regeneration through the chiasm was seen in any of the lesioned control optic nerves. In all experimental groups, large numbers of axons regenerated across the optic nerve lesions ipsilateral to the grafted eyes, traversed the short distal segment of the optic nerve and invaded the chiasm without deflection. Regeneration was correlated with the absence of the mesodermal components in the scar. In all cases, axon regrowth through the chiasm appeared to establish a major crossed and a minor uncrossed projection into both optic tracts, with some aberrant growth into the contralateral optic nerve. Axons preferentially regenerated within the degenerating trajectories from their own eye, through fragmented myelin and axonal debris, and reactive astrocytes, oligodendrocytes, microglia and macrophages. In bilaterally lesioned animals, no regeneration was detected in the optic nerve of the unimplanted eye. Although astrocytes became reactive and their processes proliferated, the architecture of their intrafascicular processes was little perturbed after optic nerve transection within either the distal optic nerve segment or the chiasm. The re-establishment of a comparatively normal pattern of passage through the chiasm by regenerating axons in the adult might therefore be organised by this relatively immutable scaffold of astrocyte processes. Binocular interactions between regenerating axons from both nerves (after bilateral optic nerve transection and intravitreal grafting), and between regenerating axons and the intact transchiasmatic projections from the unlesioned eye (after unilateral optic nerve lesions and after ipsilateral grafting) may not be important in establishing the divergent trajectories, since regenerating axons behave similarly in the presence and absence of an intact projection from the other eye.

Age Factors↗

Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance.

AIMS: Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. METHODS: After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas-liquid chromatography/mass spectrometry. RESULTS: Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) microV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6)microV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) microV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4,076 (1091) vs. 5,219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. CONCLUSIONS: Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density).

Diabetes Mellitus, Type 1↗