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 1,045 records · Page 58Linked to original sources
PubMed1988

Behavior of neurons in the abducens nucleus of the alert cat--III. Axotomized motoneurons.

The effects of peripheral and central VIth nerve axotomy on abducens nucleus synaptic potentials of vestibular origin and the ultrastructure of intracellularly labeled abducens motoneurons were examined in the anesthetized cat. Subsequent experiments explored the activity of identified abducens motoneurons during spontaneous and vestibular induced eye movements in alert cats prepared for chronic recordings of eye movements, single units and field potentials. Following axotomy the typical disynaptic inhibition of abducens motoneurons induced by electrical stimulation of the ipsilateral vestibular nerve either disappeared or was reduced for 5-30 days. Disynaptic activation produced by contralateral VIIIth nerve stimulation was apparently not affected. These changes were accompanied at the ultrastructural level by a decrease of axosomatic pleiomorphic synaptic endings. No changes were observed in either the number or distribution of synaptic endings on proximal and distal dendrites. Although not expected by results obtained in acute experiments, axotomized motoneurons showed a decreased excitability in the behavioral paradigm. Amplitude of the abducens antidromic field potential was significantly reduced 4-6 days following axotomy and frequent failures were observed in the antidromic somadendritic invasion of single motoneurons. Somatic invasion was obtained by the simultaneous presentation of appropriate visual and/or vestibular synaptic activity. Chronic recordings of field potentials showed their amplitude to recover in 30-40 days. The spontaneous and vestibular induced activity of identified axotomized motoneurons during this period of time differed in several aspects from controls. Motoneurons could not maintain tonic activity during eye fixations and they showed short, low frequency, bursts of activity that followed, rather than preceded, on-directed saccades. In some cases axotomized motoneurons fired during horizontal off-directed and vertical saccades. Position and velocity gains of axotomized motoneurons were lower than control values. The effects of central axotomy were always larger and of longer duration than those following peripheral axotomy. Structural and functional properties influenced by axotomy seemed to recover in 2-3 months, but with independent time courses. The present results differ in many aspects from those described after axotomy in spinal and hypoglossal motoneurons. In addition, they point out that behavior or axotomized neurons in chronic preparations are not predictable on the basis of those described in acute experiments.

Abducens Nerve↗
PubMed1989

Sprouts emerging from the dendrites of axotomized lamprey central neurons have axonlike ultrastructure.

We have examined the dendritic and axonal ultrastructure of intact anterior bulbar reticulospinal neurons (ABCs) in the CNS of the larval sea lamprey and compared it with that of the dendrites and neuritic sprouts from ABCs examined 2 months following axotomy. Dendrites and axons of intact ABCs are distinguishable from one another by several ultrastructural criteria: (1) the predominance of microtubules in the dendritic cytoskeleton and neurofilaments in that of the axon, (2) the exclusively postsynaptic status of the dendrites versus the presynaptic status of the axon, and (3) the presence of polyribosomes and large numbers of mitochondria in the dendrites and their respective absence and scarcity in the axon. The ultrastructure of axonal sprouts evoked by axotomy of ABCs 1-1.5 mm from their somata ("intermediate axotomy") in many ways resembled that of intact axons. Axonal sprouts were presynaptic to other neurons, and their cytoskeletons consisted mainly of neurofilaments. They also exhibited some features not seen in either axons or dendrites, such as numerous clusters of small vesicles that were not associated with synapses and, in some cases, close associations with glial elements. We also examined sprouts emerging from the dendrites of ABCs following axotomy within 500 microns of their somata ("close axotomy") and found that such "dendritic" sprouts closely resembled axonal sprouts; they possessed neurofilament-dominated cytoskeletons, were presynaptic to other neurons, and were often associated with glial elements. The dendrites of ABCs undergoing dendritic sprouting retained their normal gross morphology but possessed a mixture of "axonal" and "dendritic" ultrastructural characteristics, exhibiting neurofilament-dominated cytoskeletons while remaining entirely postsynaptic to other neurons. However, there were significantly fewer synapses on the dendrites of axotomized cells than were found on the dendrites of intact ABCs. We conclude that sprouts evoked by axotomy are intrinsically axonal in character whether they originate from the axon stump or from the dendritic tree. Our results also suggest that the materials necessary for axonal regeneration may displace elements of the dendritic cytoskeleton as they are transported through the dendrites to the emerging "dendritic" sprouts following close axotomy.

Animals↗
PubMed2004

The temporal sequence of morphological and molecular changes in axotomized feline motoneurons leading to the formation of axons from the ends of dendrites.

At 8-12 weeks post axotomy, unusual distal processes (UDPs) with axon-like structural (uniform diameter, tortuous) and molecular (growth-associated protein [GAP]43, absence of microtubule-associated protein [MAP]2a/b immunoreactivity) features emerge from distal motoneuron dendrites (Rose et al. [2001] Eur J Neurosci 13:1166-1176). In this study, we determine the time course of molecular and morphological changes associated with the formation of axons from dendrites. Motoneurons innervating neck muscles in the adult cat were permanently axotomized for 2, 4, 20, or 35 weeks and intracellularly stained with Neurobiotin. Computer-assisted reconstructions were used to map the location of MAP2a/b and GAP-43 immunoreactivity. At 2 and 4 weeks post axotomy, all UDPs had short appendages, giving them an arboreal appearance. They were immunoreactive for GAP-43 and lacked immunostaining for MAP2a/b. Axon-like UDPs were not seen until 8-12 weeks post axotomy. By 20 and 35 weeks post axotomy, some axon-like UDPs acquired morphological features of axons with synaptic connections (right-angled branching, bouton-like specializations). GAP-43 immunoreactivity was not detected in any axotomized motoneurons by 20 weeks post axotomy, whereas all UDPs remained devoid of MAP2a/b immunoreactivity even at 35 weeks post axotomy. These molecular changes accompanied structural modifications to proximal regions of "dendrites" giving rise to UDPs. The distance from the ends of the UDPs to the soma did not change. Thus, all UDPs begin as simple, arboreal structures with molecular features of growing axons, but over a period of 35 weeks, some UDPs slowly acquire morphological and molecular features of motoneuron axons with synaptic connections. These results suggest a new modus operandi for axonal growth and the establishment of new synaptic connections after injury.

Animals↗
PubMed2006

Immune-mediated neuroprotection of axotomized mouse facial motoneurons is dependent on the IL-4/STAT6 signaling pathway in CD4(+) T cells.

The CD4(+) T lymphocyte has recently been found to promote facial motoneuron (FMN) survival after nerve injury. Signal Transducer and Activator of Transcription (STAT)4 and STAT6 are key proteins involved in the CD4(+) T cell differentiation pathways leading to T helper type (Th)1 and Th2 cell development, respectively. To determine which CD4(+) T cell subset mediates FMN survival, the facial nerve axotomy paradigm was applied to STAT4-deficient (-/-) and STAT6-/- mice. A significant decrease in FMN survival 4 weeks after axotomy was observed in STAT6-/- mice compared to wild-type (WT) or STAT4-/- mice. Reconstituting STAT6-/- mice with CD4(+) T cells obtained from WT mice promoted WT levels of FMN survival after injury. Furthermore, rescue of FMN from axotomy-induced cell death in recombination activating gene (RAG)-2-/- mice (lacking T and B cells) could be achieved only by reconstitution with CD4(+) T cells expressing functional STAT6 protein. To determine if either the Th1 cytokine, interferon-gamma (IFN-gamma) or the Th2 cytokine IL-4 is involved in mediating FMN survival, facial nerve axotomy was applied to IFN-gamma-/- and IL-4-/- mice. A significant decrease in FMN survival after axotomy occurred in IL-4-/- but not in IFN-gamma-/- mice compared to WT mice, indicating that IL-4 but not IFN-gamma is important for FMN survival after nerve injury. In WT mice, intracellular IFN-gamma vs. IL-4 expression was examined in CD4(+) T cells from draining cervical lymph nodes 14 days after axotomy, and substantial increase in the production of both CD4(+) effector T cell subsets was found. Collectively, these data suggest that STAT6-mediated CD4(+) T cell differentiation into the Th2 subset is necessary for FMN survival. A hypothesis relevant to motoneuron disease progression is presented.

Animals↗
PubMed2006

Endogenous T lymphocytes and microglial reactivity in the axotomized facial motor nucleus of mice: effect of genetic background and the RAG2 gene.

Following facial nerve axotomy in mice, peripheral T cells home to the injured facial motor nucleus (FMN) where they may influence the glial response. Interactions between T cells and microglia, which proliferate in response to axotomy, appear to confer neuroprotection to injured motoneurons. The primary objective of this study was to determine whether T lymphocytes could influence the microglial reaction to motoneuron injury. These experiments tested the hypotheses that (1) C57BL/6 (B6) and 129 mice, inbred strains which have high and low levels of astroglial reactivity in the axotomized FMN, respectively, would also exhibit high and low levels of T cell infiltration, and (2) that these differences would correspond with levels of microglial reactivity and neuronal regeneration. Thus, we compared the response to facial nerve axotomy in B6, 129, and immunodeficient RAG2 knockout (RAG2 KO) mice on these two backgrounds at 14 day post-axotomy for differences in levels of 1) CD3+ T cell infiltration; (2) major histocompatibility complex II (MHC2) expression by microglia; (3) perineuronal microglial phagocytic clusters, an indirect measure of neuronal death; and (4) overall microglial activity as assessed by CD11b expression. To examine the inheritance pattern of the abovementioned neuroimmune measures, we also made assessments in B6x129 F1 generation mice. B6 and 129 mice displayed high and low levels of T cell infiltration to the affected FMN and low and high MHC2 expression, respectively. Levels of microglial activity did not differ between the two strains. In immunodeficient RAG2 KO mice on both backgrounds, the number of MHC2+ microglia did not differ from their immunologically normal background controls. Moreover, deletion of either the RAG2 or RAG1 genes in B6 mice was not associated with increased neuronal death at day 14 post-axotomy, as we had previously found in B6 mice with the severe combined immunodeficiency (SCID) mutation. Contrary to our hypothesis, the paucity of T cells in the affected FMN of the 129 mice was associated with less neuronal death when compared to B6 mice, which showed a robust T cell response. Moreover, the data suggest that parameters of the central and peripheral immune responses to axotomy are independently regulated. Assessments in B6x129 F1 generation mice revealed dominant phenotypes for both T cell infiltration and neurodegeneration, whereas both strains contributed significantly to the phenotype for MHC2 expression. Our findings suggest that (1) T cells do not appear to modify measures of microglial reactivity in the axotomized FMN; and (2) the impact of T cells on injured motoneurons in immunologically intact mice and in immunodeficient mice grafted with T cells by adoptive transfer may be different. Further study is required to understand the role of T cells following motoneuron injury in immunologically intact mice and how the seemingly divergent effects of T cells in intact and immunodeficient mice might provide insight into their role in neuronal injury and repair.

Analysis of Variance↗
PubMed2004

Effects of fimbria-fornix transection on calpain and choline acetyl transferase activities in the septohippocampal pathway.

The ability of fimbria-fornix bilateral axotomy to elicit calpain and caspase-3 activation in the rat septohippocampal pathway was determined using antibodies that selectively recognize either calpain- or caspase-cleaved products of the cytoskeletal protein alphaII-spectrin. Radioenzymatically determined choline acetyl transferase (ChAT) activity was elevated in the septum at day 5, but reduced in the dorsal hippocampus at days 3, 5 and 7, after axotomy. Prominent accumulation of calpain-, but not caspase-3-, cleaved spectrin proteolytic fragments was observed in both the septum and dorsal hippocampus 1-7 days after axotomy. ChAT-positive neuronal cell bodies in the septum also displayed calpain-cleaved spectrin indicating that calpain activation occurred in cholinergic septal neurons as a consequence of transection of the septohippocampal pathway. Calpain-cleaved alphaII-spectrin immunoreactivity was observed in cholinergic fibers coursing through the fimbria-fornix, but not in pyramidal neurons of the dorsal hippocampus, suggesting that degenerating cholinergic nerve terminals were the source of calpain activity in the dorsal hippocampus following axotomy. Accumulation of calpain-cleaved spectrin proteolytic fragments in the dorsal hippocampus and septum at day 5 after axotomy was reduced by i.c.v. administration of two calpain inhibitors. Calpain inhibition partially reduced the elevation of ChAT activity in the septum produced by transection but failed to decrease the loss of ChAT activity in the dorsal hippocampus following axotomy. These findings suggest that calpain activation contributes to the cholinergic cell body response and hippocampal axonal cytoskeletal degradation produced by transection of the septohippocampal pathway.

Animals↗
PubMed2000

Responses of nitric oxide synthase expression in the gracile nucleus to sciatic nerve injury in young and aged rats.

Neuronal nitric oxide synthase (nNOS) is induced in dorsal root ganglion neurons following axotomy in young rats, and is also increased in the gracile nucleus neurons of intact aged rats. The present study examined the influence of sciatic nerve axotomy on nNOS expression in the gracile nucleus in young compared to aged rats. The unilateral transection of the sciatic nerve was performed in young (4 months) and old (24 months) Fischer rats. Sections of rat medulla obtained 14 days after axotomy were immunolabelled using a polyclonal antibody directed against nNOS and stained by nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, a marker of nNOS activity. In young rats, unilateral axotomy produced increased NADPHd containing neurons in the rostral region and the caudal region of the ipsilateral gracile nucleus compared to the side with intact sciatic nerve. In old rats, the NADPHd containing neurons in the ipsilateral gracile nucleus were moderately increased by axotomy over the age changes seen in the contralateral side. Similar results were obtained with nNOS immunoreactivity in young rats, but more cells were seen with NADPHd staining compared to nNOS immunostaining in old rats. The results suggest that unilateral sciatic axotomy causes an increase in nNOS expression in the ipsilateral gracile nucleus of young rats, which is still seen in old rats as an increase over normal aging changes.

Aging↗
PubMed2001

Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57 BL/6J mouse: marked changes both in cell numbers and neuropeptide expression.

Several types of changes have been reported to occur in dorsal root ganglia following peripheral nerve injury, including loss of neurons and increases and decreases in peptide expression. However, with regard to loss of neurons, results have not been consistent, presumably due to different quantitative methodologies employed and species analyzed. So far, most studies have been conducted on rats; however, with the fast development of the transgenic techniques, the mouse has become a standard model animal in primary sensory research. Therefore we used stereological methods to determine the number of neurons, as well as the expression of galanin message-associated peptide, a marker for galanin-expressing neurons, neuropeptide Y, and calcitonin gene-related peptide in lumbar 5 dorsal root ganglia of both control C57 BL/6J mice and in mice subjected to a 'mid-thigh' sciatic nerve transection (axotomy). In control animals the total number of lumbar 5 dorsal root ganglion neurons was about 12000. Seven days after axotomy, 24% of the dorsal root ganglion neurons were lost (P<0.001), and 54% were lost 28 days after axotomy (P<0.001). With regard to the percentage of peptide-expressing neurons, the results obtained showed that both galanin message-associated peptide (from <1% to about 21%) and neuropeptide Y (from <1% to about 16%) are upregulated, whereas calcitonin gene-related peptide is downregulated (from about 41% to about 14%) following axotomy. Results obtained with retrograde labeling of the axotomized dorsal root ganglion neurons indicate that the neuropeptide regulations may be even more pronounced, if the analysis is confined to the axotomized dorsal root ganglion neurons rather than including the entire neuron population. We also applied conventional profile-based counting methods to compare with the stereological data and, although the results were comparable considering the trends of changes following axotomy, the actual percentage obtained with the two methods differed markedly, both for neuropeptide Y- and, especially, for galanin message-associated peptide-positive neurons. These present results demonstrate that marked species differences exist with regard to the effect of nerve injury on dorsal root ganglion neurons. Thus, whereas no neuron loss is seen in rat up to 4 weeks after a 'mid-thigh' transection [Tandrup et al. (2000) J. Comp. Neurol. 422, 172-180], the present results indicate a dramatic loss already after 1 week in mouse. It is suggested that the proximity in physical distance of the lesion to the cell body is a critical factor for the survival of the target-deprived neurons. Finally, stereological methodology seems warranted when assessing the total number of neurons as well as changes in peptide regulations after axotomy in mouse.

Animals↗
PubMed2003

Expression of auxiliary beta subunits of sodium channels in primary afferent neurons and the effect of nerve injury.

Multiple voltage-gated sodium channels are the primary mediators of cell excitability. They are multimers that consist of the pore-forming alpha subunit and auxiliary beta subunits. Although ion permeability and voltage sensing are primarily determined by the alpha subunit, beta subunits are important modulators of sodium channel function. The purpose of this study was to assess the effect of axotomy on the expression of beta subunits (beta(1), beta(2) and beta(3)) and coexpression of Na(v)1.3 and beta(3) subunits in the dorsal root ganglion (DRG). We used sciatic nerve transection models or spared nerve injury (SNI) models in the rat. In reverse transcriptase-polymerase chain reaction analysis, there were no significant differences between contralateral and ipsilateral DRGs of beta(1) and beta(2) mRNA 3 days after axotomy. beta(3) mRNA expression in ipsilateral DRGs increased significantly compared with contralateral DRGs 3 days after axotomy. In in situ hybridization histochemistry, beta(1) mRNA was predominantly expressed in medium- to large-size neurons, whereas beta(2) mRNA was expressed in small- to large-size neurons. There were no significant differences in beta(1) and beta(2) mRNA between contralateral and ipsilateral DRGs 3 days after axotomy. In contrast, beta(3) mRNA was mainly expressed in small neurons and occasionally in medium- to large-size neurons, and beta(3) mRNA expression in small c-type neurons in ipsilateral DRGs was increased significantly compared with contralateral DRGs. We examined beta(3) mRNA expression with one of alpha subunits, Na(v)1.3-ir, in DRG neurons after axotomy using the double labeling method. We found a high percentage of coexpression in injured DRG neurons: 83.6+/-2.8% of neurons expressing beta(3) mRNA were labeled for Na(v)1.3-ir; 70.1+/-3.1% of Na(v)1.3-ir neurons expressed beta(3) mRNA. We also examined the expression of beta(3) mRNA in DRG neurons in the SNI model, a neuropathic pain model. We used activating transcription factor 3 to identify axotomized neurons, and found that beta(3) mRNA up-regulation occurred mainly in axotomized neurons in the neuropathic pain model. These data strongly suggest that beta(3) expression in injured DRG neurons following axotomy might be an important pathomechanism of post-nerve injury pain in primary sensory neurons.

Activating Transcription Factor 3↗
PubMed1997

Cytoskeletal changes correlated with the loss of neuronal polarity in axotomized lamprey central neurons.

Axotomy within 500 microm of the soma (close axotomy) causes identified neurons (anterior bulbar cells or ABCs) in the lamprey hindbrain to lose their normal polarity and regenerate axons ectopically from dendritic tips, while axotomy at more distal sites (distant axotomy) results in orthotopic axonal regeneration from the axon stump. We performed immunocytochemical, electron microscopic and in situ hybridization analyses comparing ABCs subjected to close and distant axotomy to elucidate the mechanism by which neuronal polarity is lost. We show that polarity loss in ABCs is selectively and invariably preceded and accompanied by the following cellular changes: (1) a loss of many dendritic microtubules and their replacement with neurofilaments, (2) a loss of immunostaining for acetylated tubulin in the soma and proximal dendrites, and (3) an increase of immunostaining for phosphorylated neurofilaments in the distal dendrites. We also show that these changes do not depend on either the upregulation or spatial redistribution of neurofilament message, and thus must involve changes in the routing of neurofilament protein within axotomized ABCs. We conclude that close axotomy causes dendrites to undergo axonlike changes in the mechanisms that govern the somatofugal transport of neurofilament protein, and suggest that these changes require the reorganization of dendritic microtubules. We also suggest that the bulbous morphology and lack of f-actin in the tips of all regenerating sprouts supports the possibility that axonal regeneration in the lamprey CNS does not involve actin-mediated "pulling" of growth cones, but depends instead on the generation of internal extrusive forces.

Actins↗
PubMed1998

Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo.

1. The role of the cytokine leukemia inhibitory factor (LIF) in axotomy-induced sprouting of postganglionic sympathetic fibres into the dorsal root ganglia was examined in the adult rat. 2. Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase-immunoreactive (TH-IR) fibres within the lumbar dorsal root ganglia and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml-1), or 14 days following unilateral peripheral nerve axotomy. 3. In LIF-treated animals, numerous pericellular TH-IR basket-like structures were observed surrounding sensory neurones, which were absent from controls. 4. The number of TH-IR fibres within the L3, L4 and L5 spinal nerves was significantly higher in LIF-treated animals than in control or saline-treated animals (P < 0.01, Student's t test). 5. Unilateral ligation of the L4 spinal nerve or unilateral sciatic nerve ligation was also associated with the formation of TH-IR baskets around sensory neurons and a significant increase in the number of TH-IR fibres within the lumbar spinal nerves (P < 0.01, Student's t test). 6. The percentage of neurones surrounded by TH-IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml-1) (P < 0.05, Mann-Whitney U test). Antibody treatment did not reduce the axotomy-induced increase in TH-IR fibres within lumbar spinal nerves. 7. These results demonstrate that exogenous application of the axotomy-associated cytokine LIF is associated with sprouting of uninjured postganglionic sympathetic neurones around sensory neurones within the dorsal root ganglion. It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury.

Adrenergic Fibers↗
PubMed2005

Regulation of motoneuron excitability via motor endplate acetylcholine receptor activation.

Motoneuron populations possess a range of intrinsic excitability that plays an important role in establishing how motor units are recruited. The fact that this range collapses after axotomy and does not recover completely until after reinnervation occurs suggests that muscle innervation is needed to maintain or regulate adult motoneuron excitability, but the nature and identity of underlying mechanisms remain poorly understood. Here, we report the results of experiments in which we studied the effects on rat motoneuron excitability produced by manipulations of neuromuscular transmission and compared these with the effects of peripheral nerve axotomy. Inhibition of acetylcholine release from motor terminals for 5-6 d with botulinum toxin produced relatively minor changes in motoneuron excitability compared with the effect of axotomy. In contrast, the blockade of acetylcholine receptors with alpha-bungarotoxin over the same time interval produced changes in motoneuron excitability that were statistically equivalent to axotomy. Muscle fiber recordings showed that low levels of acetylcholine release persisted at motor terminals after botulinum toxin, but endplate currents were completely blocked for at least several hours after daily intramuscular injections of alpha-bungarotoxin. We conclude that the complete but transient blockade of endplate currents underlies the robust axotomy-like effects of alpha-bungarotoxin on motoneuron excitability, and the low level of acetylcholine release that remains after injections of botulinum toxin inhibits axotomy-like changes in motoneurons. The results suggest the existence of a retrograde signaling mechanism located at the motor endplate that enables expression of adult motoneuron excitability and depends on acetylcholine receptor activation for its normal operation.

Analysis of Variance↗
PubMed1994

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria-fornix transection.

Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy.

Animals↗
PubMed1996

Transplanted glial scar impedes olfactory bulb reinnervation.

The olfactory system is the only region of the mammalian central nervous system in which degeneration of the primary sensory neurons results in the development of new neurons and reinnervation of the secondary sensory neurons. Axotomy of the olfactory nerve at the cribriform plate does not cause the formation of a glial scar which blocks nerve regeneration. The purpose of this study was to determine whether a glial scar that formed in the optic nerve would suppress axonal regeneration when transplanted to the site of olfactory nerve axotomy. Primary olfactory neurons were axotomized along the cribriform plate in adult rats. A compact glial scar formed by transection of an adult rat optic nerve 50 to 60 days prior to removal was transplanted into the olfactory nerve axotomy site. The rats were allowed to survive for 1, 2, 3, or 4 weeks. Transport of horseradish peroxidase (HRP) from the nasal cavity by the olfactory neurons was used to examine the temporal and spatial pattern of regeneration of the olfactory nerve after axotomy and axotomy followed by glial scar transplantation. Twenty-one days after olfactory nerve axotomy, HRP was found in the glomerular layer where the primary olfactory axons synapse on the apical dendrites of the secondary olfactory neurons. In the presence of the transplanted glial scar, HRP labeling was not found in certain glomeruli even at 4 weeks postaxotomy. Glial scars formed within the optic nerve impede reinnervation of the olfactory bulb by neurons which have an exceptional regenerative capacity due in part to the ensheathing glia.

Age Factors↗
PubMed1996

Expression of peptides, nitric oxide synthase and NPY receptor in trigeminal and nodose ganglia after nerve lesions.

Using immunohistochemistry and in situ hybridization, the expression of galanin (GAL)/galanin message associated peptide (GMAP)-, neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI)- and nitric oxide synthase (NOS)-like immunoreactivities and mRNAs, and NPY receptor mRNA was studied in normal trigeminal and nodose ganglia and 14 and 42 days after peripheral axotomy. In normal trigeminal ganglia about 11% of the counted neuron profiles contained GAL mRNA, 4% NOS mRNA, 5% NPY mRNA, 7% VIP mRNA, and 19% NPY receptor mRNA. Peptide mRNA- and NPY receptor mRNA-positive neuron profiles were small in size. Fourteen days after axotomy a marked increase in the number of GAL mRNA-(34% of counted neuron profiles), NPY mRNA-(54%) and VIP mRNA-(31%) positive neuron profiles, and a moderate increase in the number of NOS mRNA-(22%) positive neuron profiles were observed in the ipsilateral trigeminal ganglia. The GAL/GMAP, VIP- and NOS-positive profiles were mainly small, the NPY-positive ones mostly large. NPY receptor mRNA was expressed in some large neurons. In normal nodose ganglia, about 3% of the counted neuron profiles contained GAL mRNA, 3% NPY mRNA, 17% NOS mRNA and less than 1% VIP mRNA. Fourteen days after peripheral axotomy, a marked increase in the number of GAL mRNA-(78% of counted neuron profiles), NOS mRNA-(37%) and VIP-(46%) mRNA-positive neuron profiles was seen in the ipsilateral nodose ganglia. The number of NPY-positive (23%) neurons was moderately increased, mainly in small neuron profiles. There were no NPY receptor mRNA-positive neurons, either in normal nodose ganglia or in nodose ganglia ipsilateral to the axotomy. In contralateral nodose ganglia the number of GAL- and NPY-positive neuron profiles was slightly increased, and VIP cells showed a moderate increase. Immunohistochemical analysis revealed parallel changes in expression of peptides and NOS in both trigeminal and nodose ganglia, demonstrating that the changes in mRNA levels are translated into protein. Finally, although not quantified, similar upregulations of peptide and NOS mRNA levels were observed in both ganglia 42 days after nerve injury provided that regeneration was not allowed, suggesting that the changes are long lasting. The present results show that the effect of axotomy on peptide and NOS expression in the trigeminal and nodose ganglia is similar to that previously shown for lumbar dorsal root ganglia. However, no mRNA for the NPY Y1 receptor could be detected in the vagal system. In general the mechanism(s) for and the purpose(s) of the messenger regulation in response to axotomy may be similar in these different sensory systems (dorsal root, trigeminal and nodose ganglia).

Animals↗
PubMed1985

Changes in nuclear envelope invaginations in axotomized immature and mature hamster facial motoneurons.

In this study, changes in the amount of nuclear envelope invaginations (NEI) were quantitatively assessed after axotomy during the late nuclear maturation stages (15, 20 and 25 days postnatal age) and in the adult (100-day-old) hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Absolute nuclear areas and perimeters were also estimated after axotomy at these ages. At 1/2 and 1 day after axotomy, no differences in the above parameters were noted at any of the operative ages. At 4 days postoperative, the peak of chromatolysis for all these ages, axotomy resulted in significant decreases in BA and nuclear perimeter in the immature neurons and no changes in BA and nuclear perimeter in the adult neurons. In addition, 4 days after axotomy at 20 days postnatal and later ages, pronounced increases in nuclear area occurred. These quantitative results are interpreted as evidence that the accelerated loss of NEI after axotomy during the final stages of nuclear maturation in these neurons is related to the formation of rough endoplasmic reticulum (RER) or Nissl substance. The hypothesis that an 'excess' of RER is accumulated during the late maturation stages and may account for the lack of NEI in the adult axotomized facial motoneuron is presented.

Aging↗
PubMed1992

Sympathetic nervous system modulation of tumor metastases and host defense mechanisms.

The sympathetic nervous system can signal cells of the immune system through release of norepinephrine (NE), and may thus modulate several aspects of immune reactivity. We have examined the consequences of chemical denervation using 6-hydroxydopamine (6-OHDA) on the response of BALB/c mice to tumor cell challenge. In this study, chemical axotomy prior to the intravenous (i.v.) injection of the alveolar carcinoma line 1 significantly increased the number of pulmonary metastases. In contrast, axotomy performed after i.v. injection of tumor cells had no effect on the number of lung metastases. Line 1 tumor cells have been reported to be susceptible to lysis by natural killer (NK) cells. To examine possible mechanisms through which prior axotomy leads to increased lung metastases, we tested the effects of axotomy on in vitro and in vivo NK cell activity. No differences in NK cell activity were found between 6-OHDA- and vehicle-treated mice. Line 1 tumor cell growth in vitro was unaffected by both 6-OHDA and NE, and the tumor cells do not express beta-adrenergic receptors. Priming mice with lethally irradiated line 1 cells significantly reduced the number of lung metastases following challenge with live tumor cells; axotomy did not alter this decrease in metastases associated with priming. In summary, chemical axotomy of mice prior to injection of alveolar carcinoma cells resulted in an increased number of pulmonary metastases that was not correlated with alterations in either NK cell cytotoxicity or the putative immunological consequences of in vivo priming.

Animals↗
PubMed1992

Effects of self- and cross-reinnervation on the numbers of motoneurons regenerating to forearm muscles in young and adult rats.

The present study was carried out to compare the ability of motoneurons to regenerate to functionally appropriate and inappropriate muscles, following axotomy at different stages of postnatal development. Five-, 10-, 21-day-old and adult rats of both sexes were used. In one group, the right median and radial nerves were cut and reunited. In a second group, the cut nerves were cross reunited and, in a third group the nerves were merely exposed. Following survival periods of up to one year, the extent of motoneuron regeneration through the repaired nerves was determined by injecting the retrogradely transported tracers horseradish peroxidase (HRP) and Fast Blue into the flexor and extensor muscles of the right forearm. The results were expressed in terms of the difference between the number of labelled motoneurons on the experimental side of the spinal cord and the number on the control side, the latter having been labelled by injection of HRP and Fast Blue into the muscles of the left forearm. Comparisons were then made between the groups with respect to the age at which axotomy occurred, and the target of regeneration. The results showed that when axotomy was performed in 5- and 10-day-old rats, significantly fewer motoneurons were labelled, irrespective of whether or not the target was functionally appropriate, than when axotomy was performed in adulthood. The difference was most likely due to a lower survival rate of motoneurons following axotomy in neonates. No difference was found, however, between the numbers of labelled median and radial nerve motoneurons following self- versus cross-reinnervation in any age group. This suggests that, in both adult and neonatal rats, motoneurons which survive axotomy are able to regenerate equally well to functionally appropriate or inappropriate muscles.

Aging↗