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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 21 (2005), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Clusterin is a highly conserved, amphiphatic glycoprotein present in most tissues. It has been shown to be involved in the regulation of lipid transportation, clearance of cellular debris from the extracellular space and intracellular signal transduction. Clusterin is markedly up-regulated after neural injury but the functional significance of this response is unclear. Here, we show that clusterin up-regulation is substantially greater in hypoglossal motor neurons after hypoglossal nerve avulsion compared with nerve transection. Quantitative analyses of motor neuron numbers after the same lesions in clusterin(–/–) and clusterin(+/+) mice showed significantly larger numbers of surviving motor neurons in clusterin(+/+) mice. These results suggest that clusterin has a neuroprotective role after axotomy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Functionally useful repair of the mature spinal cord following injury requires axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryonic dorsal root ganglion cells grow for long distances in adult host rat dorsal roots, traverse the interface between the peripheral and central nervous system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal cord. Dorsal root ganglia from human embryonic donors were transplanted in place of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human fibres labelled with a human-specific axon marker were distributed in superficial as well as deep laminae of the recipient rat spinal cord. About 36% of the grafted neurons were double labelled following injections of the fluorescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lumbar spinal cord, indicating that some of the grafted neurons had grown processes into the spinal cord as well as towards the denervated peripheral targets. Electrophysiological recordings demonstrated that the transplanted human dorsal roots conducted impulses that evoked postsynaptic activity in dorsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing human sensory nerve fibres which enter the adult deafferentated rat spinal cord become anatomically and physiologically integrated into functional spinal circuits.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0568
    Keywords: Primary sensory neuron ; Peripheral nerve injury ; Marchi method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The occurrence of Marchi-positive structures (MPS) in the L5 dorsal root and lumbar dorsal column was examined 1–18 weeks after unilateral sciatic nerve transection in rats, and compared to the occurrence of MPS during Wallerian degeneration seen after transection of L4 and L5 dorsal roots. There was an increasing number of MPS centrally to the junction between the peripheral (PNS) and central nervous system (CNS) and in the lumbar dorsal column ipsilateral to sciatic nerve transection throughout the examined time period. In the portion of the root distal to the PNS-CNS junction MPS were rare before 12 weeks postoperatively after which time small groups of MPS appeared. At all stages the incidence of MPS was just a fraction of that seen during Wallerian degeneration. From these observations it is inferred that few ganglion cells with myelinated central processes undergo complete disintegration after peripheral nerve transection. In addition, some of the myelinated central ganglion cell processes appear to be more severely affected proximal to the PNS-CNS junction than distally to it.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0568
    Keywords: Spinal nerves ; Dorsal column nuclei ; Nerve degeneration ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural changes in the gracile nucleus of the rat have been examined after peripheral nerve injury. The sciatic nerve of adult rats was transected at mid-thigh level, and after survival times ranging from 1 day to 32 weeks sections from the gracile nucleus were prepared for electron microscopic examination. Unoperated animals served as controls. Atypical profiles were regularly observed in the experimental cases at post-operative survival times from 3 days up to 32 weeks. It was sometimes not possible to classify these as pre-terminal axons or terminals, because synaptic contacts could not be identified. The two most common changes throughout the entire post-operative period were greatly expanded myelinated axons, or unmyelinated profiles containing numerous mitochondria, osmiophilic dense bodies and vacuoles. Atypical profiles were occasionally observed in unoperated control animals. The results clearly show that various types of degenerative changes occur in the gracile nucleus after peripheral nerve injury. These changes differ markedly from previously described transganglionic changes in other systems. It cannot be excluded that some of the changes reflect growth-related reactions, although the typical features of axon regeneration could not be found.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 169 (1984), S. 303-307 
    ISSN: 1432-0568
    Keywords: Neuroglia ; Axon injury ; Motor neurons ; CNS ; Species specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of axotomy on the numbers and density of perineuronal cell populations was evaluated in rats, cats and kittens. Cats were sacrificed at different postoperative time intervals two through 90 days after unilateral plexotomy. Kittens (6–10 weeks of age) were subjected to the same surgical procedure and sacrificed one through 28 days after surgery. Rats were sacrificed 10 and 15 days after unilateral lateral section of the brachial plexus or at 7 or 10 days after section of the left hypoglossal nerve. A marked increase in the total number and density of perineuronal cells occurred in the rat ventral horn 10 and 15 days after axotomy. A similar response was noted in the rat hypoglossal nucleus 7 and 10 days after neurotomy. In contrast, no significant change in these parameters was observed in the ventral horns of cats and kittens at any of the postoperative time intervals. Although quantitatively demonstrable increases in the perineuronal cell populations occur in the ventral horns and hypoglossal nuclei of rats, similar modifications do not occur in the cat following axon injury. These findings suggest that evolutionary modifications may have occurred in how perineuronal glia respond to peripheral axon injury.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Peripheral nerve injury ; Glabrous skin ; Sensory nerve endings ; Neuropeptide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into “foreign” denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory. This was also the case when the saphenous nerve had been crushed and allowed to regenerate in rats injured neonatally, or as adults. However, judging from previous physiological data, the regenerating axons do not develop into functional low-threshold mechanoreceptors.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1106
    Keywords: Trigeminal nuclear complex ; Plasticity ; Mechanoreceptor afferents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous light and electron microscopic studies in rat and cat have shown that transection of peripheral sensory nerve branches leads to alterations in the central branches of primary sensory neurons, so-called transganglionic changes. In this study the changes in choleragenoid (B)-horseradish peroxidase B-HRP-labeled primary sensory terminals and axons in the trigeminal nuclear complex 3–90 days following transection of vibrissae nerves in the rat have been studied. Since regeneration of the transected vibrissa nerve was not prevented, these experiments allowed the examination of degenerative changes in the earlier stage after nerve injury as well as those present during nerve regeneration and target reinnervation. Two different experimental approaches were used, depending on the postlesion survival time. For short-term experiments the deep vibrissa nerve was injected with a solution of B-HRP. Forty-eight hours later the nerve was transected at its entry in the follicle, and after survival times ranging from 3 to 15 days sections from the subnucleus caudalis and spinal trigeminal nucleus, were prepared for electron microscopic examination. For long-term experiments involving a 16- to 90-day posttransection survival time, the deep vibrissa nerve was cut first. Then B-HRP was injected into the reinnervated follicle 2 days before killing the rats. Atypical HRP-labeled terminals were seen from 4 to 90 days survival time. The changes observed included atypical swollen vesicles or lack of vesicles in parts of the terminals apposed to the synaptic cleft. Other terminals displayed dense clusters of vesicles, flocculent cytoplasm, and/or neurofilamentous hyperplasia. No evidence of complete disintegration or phagocytosis by glial cells was observed. From 4 to 12 days survival time the changes were most commonly seen in the larger terminals, from 19–90 days in smaller terminals. From 10 days survival time and onward, changes in axons were observed. The most commonly seen alterations were axons with expanded myelin sheaths. Normal-labeled terminals were seen at all survival times examined. Compared with earlier studies of transganglionic changes in the vibrissa system occurring after infraorbital nerve or vibrissa row nerve injury, the changes seen in this study are less pronounced. These observations indicate (1) that the initial changes in the central processes of peripherally injured vibrissae nerves are less extensive than those occurring after infraorbital nerve transection, possibly because of the distally located lesion, and (2) that transganglionic changes occur also after the injured nerve has regenerated.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1106
    Keywords: Key words Neuroglia ; Astrocytes ; Degeneration ; Brain stem ; Neurotrophin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The time course of the astroglial cell reaction in the nucleus gracilis and the spinal cord dorsal horn was examined following sciatic nerve transection in the adult rat with qualitative and quantitative analysis of glial fibrillary acidic protein immunoreactivity and in situ hybridization for its mRNA. In addition, the potential effect of exogenous nerve growth factor (NGF) was examined on the astroglial and microglial cells in the spinal cord dorsal horn at certain time points following sciatic nerve transection. An increase in glial fibrillary acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day after lesioning, with a peak at about 1 week and 2 days after lesioning, respectively, followed by a decline. However, NGF application during 1, 2 and 4 weeks following nerve transection did not result in any significantly reduced astroglial or microglial activity. Our results show that the astroglial cell response in the nucleus gracilis and the spinal cord dorsal horn is rapid in comparison with previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration), that the astroglial cell reaction develops concomitantly with the microglial cell reaction previously described and that the „signal” from the axotomized neurons which induces these reactions can not be prevented by exogenous NGF applied to the peripheral nerve.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Summary The ultrastructural localization of immunoreactivity for immunoglobulin G (IgG), F(ab′)2 and complement C9 was examined with preembedding immunoelectron microscopy in the hypoglossal nucleus and gracile nucleus as well as in the L4 spinal cord dorsal horn 1 week following hypoglossal or sciatic nerve transection, respectively. Only a few scattered immunoreactive profiles were observed on the unoperated side. On the operated side, IgG and F(ab′)2 immunoreactivity was present in the membranes of all reactive microglial cells observed. In addition, the cell membrane of some hypoglossal motoneurons showed IgG immunoreactivity. Complement C9 immunoreactivity was present in the cytoplasm of all reactive microglial cells examined. In addition, there was diffuse C9 immunoreactivity in motoneuron perikarya ipsilateral to nerve injury as well as in cell membranes in the neuropil, some of which could be identified as neuronal. Our interpretation of these findings is (1) that peripheral nerve injury results in binding of IgG to reactive microglia, as well as to some axotomized neurons, and (2) that C9 is synthesized by reactive microglia in response to axon injury and is also associated with axotomized motoneurons. These findings suggest that IgG and complement C9 are involved in microglia-neuron interactions after peripheral nerve injury.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurocytology 7 (1978), S. 229-250 
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Trigeminal ganglia of normal rats and of adult rats subjected to unilateral transection of the infraorbital nerve were studied by light and electron microscopy. Counts of ganglion cells in ganglia on operated and unoperated sides were made following long postoperative survival times. The ultrastructural changes in ganglia of the operated side were studied from 3 to 70 days postoperatively. The quantitative observations show that a considerable loss of ganglion cells takes place on the operated side. The ultrastructural observations demonstrate the occurrence of ganglion cell degeneration, nerve fibre degeneration and phagocytosis by satellite and Schwann cells. The results are compatible with the view that degeneration of trigeminal afferents in the brain stem following lesions of peripheral trigeminal nerve branches is related to retrograde degeneration of trigeminal ganglion cells.
    Type of Medium: Electronic Resource
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