Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Axotomy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1993

Immature corticospinal neurons respond to axotomy with changes in tubulin gene expression.

We have examined the expression of two different tubulin mRNAs in hamster corticospinal neurons that were axotomized at three different developmental stages; postnatal day 8 (P8), P20, and adult. In situ hybridization of histological sections of the sensorimotor cortex was done with 35S-labeled cDNA probes specific to alpha 1-tubulin and beta III-tubulin mRNAs at 2-14 days following unilateral transection of the corticospinal tract in the caudal medulla. Both film and emulsion autoradiography were used to detect changes in tubulin mRNA levels. Qualitative assessment indicated substantial decreases in both alpha 1-tubulin and beta III-tubulin mRNA levels in layer V neurons of the sensorimotor cortex following axotomy. The changes were apparent as early as 2 days postinjury for P20 and adult operates, but not for P8 operates. However, by 14 days postinjury, decreases in alpha 1-tubulin and beta III-tubulin gene expression were apparent in animals operated at all three developmental stages. These findings indicate that both immature and adult corticospinal neurons respond to axonal injury in a manner that is distinctly different from the peripheral neuron response.

Animals↗
PubMed2006

The expression of a motoneuron-specific serine protease, motopsin (PRSS12), after facial nerve axotomy in mice.

Motopsin (PRSS12) is a mosaic serine protease that is preferentially expressed in motor neurons. To study the relationship between motopsin and motoneuron function, we investigated the expression of motopsin mRNA in facial nerve nuclei after facial nerve axotomy at the anterior margin of the parotid gland in mice. Neuronal function was monitored by assessing vibrissal motion in 3 months. Vibrissal behaviour on the injured side disappeared until the day 14 post-operation, and then recovered between the day 21 and 35. Motopsin expression decreased at the day 14, but markedly recovered by the day 21. In contrast, expression of growth-associated protein-43 (GAP-43) was induced at the day 3. These results suggest that the recovery of motopsin expression is correlated with the recovery of the facial motor neuronal function.

Animals↗
PubMed1993

Fine structural correlates of VIP-like immunoreactivity in the upper spinal dorsal horn after peripheral axotomy: possibilities of a neuro-glial translocation of a neuropeptide.

After transection of the peripheral nerve, VIP-like immunoreactivity (VIPLI) increases markedly in the ipsilateral upper dorsal horn of the spinal cord. Immunoreactivity has been studied by means of light- and electron microscopic immunocytochemistry. Under normal conditions, there is little VIPLI present in the superficial dorsal horn, confined to small dot-like elements corresponding to axonal and glial profiles. At the electron microscopic level, immunostaining was found mainly in preterminal and, partly, also in en passant terminal swellings or varicosities. The reaction was confined to the axoplasm and, to a lesser extent, to large dense core vesicles. VIPLI is also present in several astroglial processes. 13, 19, and 25 d after transection of the sciatic nerve, increased immunoreactivity was present in the medial 2/3 of the superficial dorsal horn. Electron microscopically, VIPLI was seen mainly in preterminal axons and in many astroglial processes surrounding axon terminals while VIPLI in the en passant axon terminals themselves decreases. 2 months after peripheral axotomy, the amount of axonally localized VIPLI decreases considerably and most of the immunocytochemically detectable VIPLI is found in expansions and processes of astroglial cells. Perikarya of glial cells rarely exhibit VIPLI. VIPLI also increased after crushing the related peripheral nerve; however, as soon as the nerve fibers regenerate, VIPLI decreases again to normal levels. It appears that blockade of the retrograde axoplasmic transport induces a switch in the neuropeptide synthesizing machinery of dorsal root ganglion cells which results in the expression of VIP instead of substance P, somatostatin and CGRP. It is proposed that VIP is released from axon terminals affected by transganglionic degenerative atrophy. Subsequently, astroglial cells equipped with receptors for VIP, might bind and internalize the released VIP.

Animals↗
PubMed1996

Region-specific central nervous system expression and axotomy-induced regulation in sympathetic neurons of a VIP-beta-galactosidase fusion gene in transgenic mice.

To assess the activity of cis-acting elements that direct human vasoactive intestinal peptide (VIP) expression in vivo, two independent transgenic mouse lines were created using a transgene comprised of 1.9 kb of 5'-flanking sequence of the human VIP gene joined to the Escherichia coli beta-galactosidase reporter gene. Transgene expression in brain was assessed using beta-galactosidase histochemistry and compared to the distribution of endogenous VIP expression. Transgene expression was observed in most central and peripheral nervous system sites in which endogenous VIP is expressed. We investigated whether the VIP-beta-galactosidase transgene was regulated in sympathetic neurons in experimental paradigms in which VIP regulation is dependent on the release of leukemia inhibitory factor (LIF). After dissociation in vitro and postganglionic axotomy in vivo there were parallel increases in endogenous VIP and transgene expression in superior cervical ganglia. These results indicate that the 1.9 kb region of 5'-flanking sequence of the human VIP gene includes genomic elements important for cell-specific expression and LIF-dependent regulation in neurons.

Animals↗
PubMed1996

Increased expression of the alpha subunit of the ciliary neurotrophic factor (CNTF) receptor by rat racial motoneurons after neonatal axotomy and CNTF treatment.

Expression by rat motoneurons of mRNAs for the alpha subunit of the ciliary neurotrophic factor receptor (CNTFR alpha), receptor tyrosine kinase-C (trkC), calcitonin gene-related peptide (CGRP) and galanin was studied by in situ hybridisation, 6d after rat facial nerve transection on postnatal day 1. Similar numbers of motoneurons in both injured and non-injured nuclei hybridised with all probes, despite a reduction in total numbers of motoneurons ipsilaterally. When ciliary neurotrophic factor (CNTF) was applied to the proximal nerve, twice as many motoneurons in the injured nucleus hybridised with the CNTFR alpha probe ipsilaterally compared to the non-injured nucleus, while motoneuronal loss was not evident. These results indicate that survival of motoneurons after neonatal axotomy and CNTF treatment is associated with increased CNTF receptor alpha expression.

Animals↗
PubMed1997

Reduced sympathetic sprouting occurs in dorsal root ganglia after axotomy in mice lacking low-affinity neurotrophin receptor.

Following sciatic nerve injury, sympathetic axons sprout into the L5 dorsal root ganglion (DRG). The low-affinity neurotrophin receptor (p75) is strongly expressed by glial cells in DRG following axotomy. We tested the hypothesis that p75 is involved in this sympathetic sprouting by comparing sprouting following sciatic nerve cut in wild-type (CD1) and p75 knockout mice. Twenty-one days after injury sympathetic sprouting had occurred in both mouse strains, though the extent of sprouting (measured as length of sprouts per unit area of DRG) was less in p75 knockout mice. We conclude that p75 expression enhances, but is not required for, sympathetic sprouting.

Animals↗
PubMed1997

Identification and characterization of a novel gene (neurorep 1) expressed in nerve cells and up-regulated after axotomy.

A novel gene, designated neurorep 1, was isolated by differential hybridization screening from a complementary DNA library constructed from the rat facial nucleus whose nerve had been transected seven days before sampling. In situ hybridization revealed that this gene was up-regulated in the repair stage after axotomy. The deduced protein, Neurorep 1, consists of 293 amino acid residues, and its molecular mass is approximately 34,000. Protein sequence motif search indicates that this protein has an ecto-5'-nucleotidase consensus sequence at the carboxyl terminal region. In vitro studies showed that Neurorep 1 significantly increased the activity of ecto-5'-nucleotidase, which is considered to be involved in regeneration and repair of the central nervous system. Neurorep 1 might play a significant role in the repair process of nerve tissues by its regulation of ecto-5'-nucleotidase activity.

5'-Nucleotidase↗
PubMedDate not supplied

Receptive-field properties of displaced starburst amacrine cells change following axotomy-induced degeneration of ganglion cells.

Starburst amacrine cells in the rabbit retina were labeled following an intraocular injection of the fluorescent dye, 4,6,diamidino-2-phenylindole (DAPI). From each eye a strip of retina was removed, mounted on a platform beneath an epifluorescence microscope, and superfused with a physiological solution. The tip of a tungsten microelectrode (for extracellular recording) was visually positioned near the cell body of a DAPI-labeled starburst amacrine cell that was located in the ganglion cell layer. Light-evoked responses from the displaced starburst amacrine cells were studied in normal retinas and in retinas that had received a small electrolytic lesion near the optic disk 5-9 months beforehand. In normal retinas, a small spot of light centered over the receptive field of a displaced starburst amacrine cell in nearly all cases evoked a brief burst of spikes only at light onset. When stimulated with a large spot or an annulus of light, many cells gave a small burst of spikes at light offset. In lesioned retinas, the light responses of displaced starburst amacrine cells were recorded in areas of the retina where ganglion cells had degenerated. All cells responded with a large burst of spikes at the onset and offset of a small, centered spot of light. Large spots and annuli of light also evoked robust ON/OFF responses from these cells. The results from this study show that the receptive-field properties of displaced starburst amacrine cells change following axotomy-induced degeneration of ganglion cells. This finding indicates that changes in either synaptic transmission or the membrane properties of neurons occur in the retina following degeneration of ganglion cells.

Action Potentials↗
PubMed1997

Gonadal steroid preservation of central synaptic input to hamster facial motoneurons following peripheral axotomy.

In recent work, we have demonstrated that testosterone propionate accelerates recovery from facial nerve injury in the adult male hamster. Central synaptic stripping following peripheral motor neuron damage is a well-established component of the injury response. Gonadal steroids regulate synaptogenesis in the normal nervous system. In this study, we tested the hypothesis that testosterone propionate administration at the time of facial nerve transection alters the synaptic connectivity of injured facial motoneurons. Adult hamsters were subjected to right facial nerve transection at the level of the stylomastoid foramen. Half the animals received subcutaneous implants of testosterone propionate; the other half were sham implanted. At 5 days postoperative, the animals were killed by intracardiac perfusion-fixation, and the control and axotomized facial nuclear groups from the brainstems of nonhormone- and testosterone propionate-treated animals processed for routine transmission electron microscopy. Quantiative analysis of the synaptic ratio (percent somal membrane covered by synaptic profiles) and the average length of axosomatic synapses was accomplished. The results indicate that axotomy alone resulted in an 81% reduction in the synaptic ratio and a 26% decrease in the average synaptic length of axosomatic synapses. Exposure to testosterone propionate from the time of facial nerve transection resulted in only a 48% reduction in the synaptic ratio and a 16% decrease in the average synaptic length of axosomatic synapses following injury. Thus, testosterone propionate significantly attenuated the amount of synaptic stripping that occurred at 5 days postoperative and the decrease in average length of the remaining synapses as well. It is concluded that gonadal steroids modulate central synaptic plasticity following peripheral nerve injury. The results are discussed in light of our recent findings of steroidal effects on the central astrocyctic response to facial nerve injury as well.

Animals↗
PubMed1990

Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.

The period of natural cell death in the development of rodent motor neurons is followed by a period of sensitivity to axonal injury. In the rat this early postnatal period of vulnerability coincides with that of very low ciliary neurotrophic factor (CNTF) levels in the sciatic nerve before CNTF increases to the high, adult levels. The developmental time course of CNTF expression, its regional tissue distribution and its cytosolic localization (as suggested by its primary structure) favour a role for CNTF as a lesion factor rather than a target-derived neurotrophic molecule like nerve growth factor. Nevertheless CNTF exhibits neurotrophic activity in vitro on different populations of embryonic neurons. To determine whether the vulnerability of motor neurons to axotomy in the early postnatal phase is due to insufficient availability of CNTF, we transected the axons of newborn rat motor neurons and demonstrated that local application of CNTF prevents the degeneration of the corresponding cell bodies.

Animals↗
PubMedDate not supplied

Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death.

Current ideas about the dependence of neurons on target-derived growth factors were formulated on the basis of experiments involving neurons with projections to the periphery. Nerve growth factor (NGF) and recently identified members of the NGF family of neuronal growth factors, known as neurotrophins, are thought to regulate survival of sympathetic and certain populations of sensory ganglion cells during development. Far less is known about factors that regulate the survival of spinal and cranial motor neurons, which also project to peripheral targets. NGF has not been shown to influence motor neuron survival, and whether the newly identified neurotrophins promote motor neuron survival is unknown. We show here that brain-derived neurotrophic factor (BDNF) is retrogradely transported by motor neurons in neonatal rats and that local application of BDNF to transected sciatic nerve prevents the massive death of motor neurons that normally follows axotomy in the neonatal period. These results show that BDNF has survival-promoting effects on motor neurons in vivo and suggest that BDNF may influence motor neuron survival during development.

Animals↗
PubMed1995

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.

Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Animals↗
PubMed1995

Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF.

During normal development of the vertebrate nervous system, large numbers of neurons in the central and peripheral nervous system undergo naturally occurring cell death. For example, about half of all spinal motor neurons die over a period of a few days in developing avian, rat and mouse embryos. Previous studies have shown that extracts from muscle and brain, secreted factors from glia, as well as several growth factors and neurotrophic agents, including muscle-derived factors, can promote the survival of developing motor neurons in vitro and in vivo. But because neurotrophins and other known trophic agents administered alone or in combination are insufficient to rescue all developing motor neurons from cell death, other neurotrophic molecules are probably essential for the survival and differentiation of motor neurons. Here we report that glial-cell-line-derived neurotrophic factor (GDNF), a potent neurotrophic factor that enhances survival of mammalian midbrain dopaminergic neurons, rescues developing avian motor neurons from natural programmed cell death in vivo and promotes the survival of enriched populations of cultured motor neurons. Furthermore, treatment with this agent in vivo also prevents the induced death and atrophy of both avian and mouse spinal motor neurons following peripheral axotomy.

Animals↗
PubMed1994

The ability of diphenylpiperazines to prevent neuronal death in dorsal root ganglion neurons in vitro after nerve growth factor deprivation and in vivo after axotomy.

The mechanism of neuroprotection by the calcium channel antagonist flunarizine against neuronal death is unknown. We investigated the ability of other calcium channel antagonists (cinnarizine, nimodipine, nicardipine, diltiazem, and verapamil), calmodulin antagonists, and calpain inhibitors to prevent neuronal death in rat dorsal root ganglion neurons in vitro after nerve growth factor (NGF) deprivation and the ability of cinnarizine and diltiazem to protect in vivo after axotomy. In vitro, only neurons treated with cinnarizine or flunarizine were protected from death after withdrawal. In vivo, cinnarizine, but not diltiazem, protected dorsal root ganglion neurons in rats after unilateral sciatic nerve crush. Intracellular calcium concentration ([Ca2+]i) was evaluated with fura 2 after NGF deprivation in vitro. Neurons "committed to die" 24 h after NGF deprivation displayed a decline in [Ca2+]i before visible morphological deterioration consistent with cell death. The influx of extracellular calcium was not necessary to produce neuronal death. Neurons deprived of NGF gradually lost the ability to respond to elevated external potassium with an increase in [Ca2+]i during the first 24 h after trophic factor deprivation. After 24 h, neurons deprived of NGF could not be rescued by readministration of NGF. Neurons protected from cell death with diphenylpiperazines maintained their response to high external potassium, suggesting continued membrane integrity. We speculate that diphenylpiperazines may protect sensory neurons via an unknown mechanism that stabilizes cell membranes.

Animals↗
PubMed1986

Induction of nerve growth factor receptor in Schwann cells after axotomy.

We have discovered that axotomy of sciatic nerve induces Schwann cells distal to the lesion to express de novo, or at greatly increased levels, receptors for nerve growth factor (NGF). Surgical transection of sciatic nerve was performed on adult Sprague-Dawley rats, and, at various times after the operation, the following tissues were dissected for quantitation of NGF receptor: L4 and L5 dorsal root ganglia, sciatic nerve proximal to the transection, sciatic nerve distal to the transection, tibialis anterior muscle, and skin of the dorsum of the foot. The NGF receptor content of these samples was determined by labeling receptor molecules with radioiodinated NGF (125I-NGF) and then specifically immunoprecipitating the 125I-NGF-receptor complexes with 192-IgG, a monoclonal antibody directed against the rat NGF receptor. We observed a time-dependent increase in the amount of radioligand-labeled NGF receptor proteins found in the distal segment of transected sciatic nerve; by 7 days the density of receptor (crosslinked 125I-NGF molecules per mg of homogenate protein) had increased at least 50-fold. The number of receptor molecules in tibialis anterior muscle and dorsal foot skin, two structures denervated by the transection, also increased, with time courses parallel to that of distal sciatic nerve. There was little increase in the density of NGF receptors in the sciatic nerve proximal to the lesion and in the dorsal root ganglia. Immunohistochemical examination of the distal portion of transected sciatic nerve and of the muscle, with 192-IgG as the primary ligand, revealed prominent and exclusive staining of apparently all Schwann cells of the endoneurium, indicating that these peripheral neuroglial cells were expressing NGF receptors. These results show that axonal damage can induce the expression of NGF receptors in the population of sheath cells thought to promote neuronal regeneration. This dramatic increase in NGF receptors may be a mechanism to facilitate the regeneration of NGF-responsive neurons.

Animals↗
PubMed1992

Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies.

Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites.

Amino Acid Oxidoreductases↗
PubMed1994

Axotomy induces the expression of vasopressin receptors in cranial and spinal motor nuclei in the adult rat.

8-L-Arginine vasopressin ([Arg8]VP) receptors are expressed transiently in the rat facial nucleus during the perinatal period. Electrophysiological studies suggest that at least part of these receptors is located on facial motoneurones. In the present study we report that, in the adult rat, unilateral section of a facial nerve results in a massive and transient reexpression of [Arg8]VP receptors in the deeferented facial nucleus. Data were obtained by quantitative film autoradiography. During the first 2 postoperative weeks, binding of an iodinated ligand selective for V1a-type receptors increased about 10-fold. Maximal levels of binding were maintained for 1-2 weeks and then started to decrease. Binding was not strictly restricted to the facial nucleus but included the neuropile between motoneuronal pools and the perifacial area, which may indicate a dendritic localization of [Arg8]VP receptors. To investigate whether other motor nuclei also react to axotomy by up-regulating [Arg8]VP receptors, we sectioned either a hypoglossal nerve or a sciatic nerve. Two weeks after surgery, the hypoglossal nucleus or sciatic motoneuronal pools ipsilateral to the lesion were intensely labeled with the iodinated ligand. In contrast, nerve section had no effect on oxytocin binding sites in facial, hypoglossal, or sciatic motor nuclei. The results suggest that [Arg8]VP receptor expression in motor nuclei may depend upon neuromuscular contacts and, thus, that [Arg8]VP may be involved in the establishment of neuromuscular connections during development and in their reestablishment after nerve injury.

Amino Acid Sequence↗
PubMed1994

Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death.

In vitro, the overexpression of the bcl-2 protooncogene in cultured neurons has been shown to prevent apoptosis induced by neurotrophic factor deprivation. We have generated transgenic mice overexpressing the Bcl-2 protein in neurons, including motoneurons of the facial nucleus. We have tested whether Bcl-2 could protect these motoneurons from experimentally induced cell death in new born mice. To address this question, we performed unilateral lesion of the facial nerve of wild-type and transgenic 2-day-old mice. In wild-type mice, the lesioned nerve and the corresponding motoneuron cell bodies in the facial nucleus underwent rapid degeneration. In contrast, in transgenic mice, facial motoneurons survived axotomy. Not only their cell bodies but also their axons were protected up to the lesion site. These results demonstrate that in vivo Bcl-2 protects neonatal motoneurons from degeneration after axonal injury. A better understanding of the mechanisms by which Bcl-2 prevents neuronal cell death in vivo could lead to the development of strategies for the treatment of motoneuron degenerative diseases.

Animals↗