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At least 19 recordsLinked to original sources

PubMed2002

Changes in Na(+) channel currents of rat dorsal root ganglion neurons following axotomy and axotomy-induced autotomy.

Section of rat sciatic nerve (axotomy) increases the excitability of neurons in the L(4)-L(5) dorsal root ganglia (DRG). These changes are more pronounced in animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine changes in the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) components of sodium channel currents (I(Na)) that may contribute to axotomy-induced increases in excitability. Cells were initially divided on the basis of size into "large," "medium," and "small" groups. TTX-S I(Na) predominated in "large" cells, whereas TTX-R I(Na) predominated in some, but not all "small cells." "Small" cells were therefore subdivided into "small-slow" cells, which predominantly exhibited TTX-R I(Na) and "small fast" cells that exhibited more TTX-S I(Na). In contrast to results obtained in other laboratories, where slightly different experimental procedures were used, we found that axotomy increased TTX-R and/or TTX-S I(Na) and slowed inactivation. The effects were greatest in "small-slow" cells and least in "large" cells. The changes promoted by axotomy were expressed more clearly in animals that exhibited autotomy. Also, the presence of autotomy correlated with a shift in the properties of I(Na) in "large" rather than "small-slow," putative nociceptive cells. These trends parallel previous observations on axotomy-induced increases in excitability, spike height, and spike width that are also greatest in "small" cells and least in "large" cells. In addition, the presence of autotomy correlates with an increase in excitability of "large" rather than "small" cells. Increases in TTX-R and TTX-S I(Na) thus coincide with axotomy-induced increases in excitability and alterations in spike shape across the whole population of sensory neurons. Injury-induced changes of this type are likely associated with the onset of chronic pain in humans.

Animals↗

PubMed2000

Caspase-3 is activated following axotomy of neonatal facial motoneurons and caspase-3 gene deletion delays axotomy-induced cell death in rodents.

In this report, we examined the possible functions of the cell death protease, caspase-3, in the axotomy-induced apoptosis of facial motoneurons in newborn rodents. Using in situ hybridization and Western blot, we found higher levels of caspase-3 mRNA and pro-caspase-3 protein expression in motoneurons of neonatal and 2-week-old rats than adult rats. Following facial motoneuron axotomy, caspase-3 mRNA and protein expression increased in motoneurons of both neonatal and adult rats. However, using an antibody directed to the activated form of the caspase-3 protease, we found that catalytically active caspase-3 was present only in axotomized neonatal motoneurons. As motoneurons in neonatal but not adult rodents are susceptible to axotomy-induced apoptosis, we hypothesized that caspase-3 may play a role in their demise. To determine the necessity of caspase-3 activation in axotomy-induced apoptosis, we counted the number of surviving motoneurons at 4 and 7 days following axotomy in wild type mice and caspase-3 gene-deleted mice. There were nearly three times more surviving motoneurons in caspase-3 gene-deleted mice than in wild type mice at both 4 days (mean 1074 vs. 464, P<0.005) and 7 days (mean 469 vs. 190, P<0.005) following injury, indicating a slower rate of death. Examination of the dying motoneurons using TUNEL staining (for fragmented DNA) and bisbenzimide staining (for nuclear morphology) revealed incomplete nuclear condensation in caspase-3-deficient motoneurons. These results demonstrate that caspase-3 activation plays important roles in the rapid demise of axotomized neonatal motoneurons.

Age Factors↗

PubMed1983

'Zap axotomy': localized fluorescent excitation of single dye-filled neurons induces growth by selective axotomy.

The response of populations of neurons to axotomy has traditionally been studied by crushing or sectioning whole nerve trunks. The present communication describes a technique by which single neurons can be reliably and selectively axotomized in the absence of damage to other axons and non-neuronal cells within the nerve. To obtain selective axotomy, identified neurons of the buccal ganglia of the snail, Helisoma, were first filled with fluorescent dye. Next, the preparation was positioned in a restricted beam of blue light using low light video fluorescence microscopy. Finally, the selected region of axon was briefly exposed to light levels normally employed for fluorescence microscopy. Shortly after irradiation of the identified neuron 5, antidromic action potentials no longer propagated past the region of exposure in the dye-filled cell, whereas adjacent axons were physiologically intact. Several days after exposure, profuse neurite outgrowth was observed from the proximal region of axon of neuron 5, but never in neighboring axons which were not filled with dye at the time of irradiation. When the axons of both neurons 5R and 5L were spot irradiated neurite outgrowth resulted in the formation of a novel electrical connection between these cells. These changes in growth and connectivity which were induced by selective axotomy of single axons were indistinguishable from the changes which are produced by crushing entire nerve trunks.

Animals↗

PubMed1988

Neurofilament protein synthesis in DRG neurons decreases more after peripheral axotomy than after central axotomy.

Cytoskeletal protein synthesis was studied in DRG neurons after transecting either their peripheral or their central branch axons. Specifically, the axons were transected 5-10 mm from the lumbar-5 ganglion on one side of the animal; the DRGs from the transected side and contralateral control side were labeled with radiolabeled amino acids in vitro; radiolabeled proteins were separated by 2-dimensional (2D) PAGE; and the amounts of radiolabel in certain proteins of the experimental and control ganglia were quantified and compared. We focused on the neurofilament proteins because they are neuron-specific. If either the peripheral or central axons were cut, the amounts of radiolabeled neurofilament protein synthesized by the DRG neurons decreased between 1 and 10 d after transection. Neurofilament protein labeling decreased more after transection of the peripheral axons than after transection of the central axons. In contrast to axonal transections, sham operations or heat shock did not decrease the radiolabeling of the neurofilament proteins, and these procedures also affected the labeling of actin, tubulin, and the heat-shock proteins differently from transection. These results and others indicate that axonal transection leads to specific changes in the synthesis of cytoskeletal proteins of DRG neurons, and that these changes differ from those produced by stress to the animal or ganglia. Studies of the changes in neurofilament protein synthesis from 1 to 40 d after axonal transection indicate that the amounts of radiolabeled neurofilament protein synthesis were decreased during axonal elongation, but that they returned toward control levels when the axons reached cells that stopped elongation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1981

Ionic and metabolic dependence of axotomy-induced somatic membrane changes in crayfish.

1. Axotomy induces a transient change in the soma membrane from non-spiking to spiking in many neurones of the crayfish abdominal C.N.S. The ionic and metabolic dependence of this phenomenon was investigated in one identified neurone. 2. The inward current of axotomy-induced soma spikes is carried primarily by Na ions. 3. Addition of 50 mM-tetraethylammonium to the external saline unmasks predominantly Ca-mediated soma spikes in control cells. The calcium spikes are not affected by axotomy. 4. Axotomy induces a transient increase in delayed rectification of the soma membrane. 5. Membrane potential is dependent on the external potassium concentration as predicted by the Nernst function while external sodium has essentially no effect. This is not changed following axotomy. 6. The inward current of the axon spike is primarily carried by sodium ions both before and after axotomy. The overshoot of the axon spike is not dramatically changed between the time when axotomy-induced soma spikes are present and when they have disappeared. 7. Following axotomy, both the onset and offset of axotomy-induced soma spikes occur earlier when the temperature is raised by 10 degrees C. 8. Cycloheximide retards or prevents soma spikes normally seen following axotomy. 9. The results indicate that axotomy induces a transient increase in voltage-dependent Na and K conductances but not Ca conductance, and that these changes are dependent on axotomy-inhibited protein synthesis.

Action Potentials↗

PubMed1999

Reciprocal changes in the expression of Bcl-2 and Bax in hypoglossal nucleus after axotomy in adult rats: possible involvement in the induction of neuronal cell death.

Numerous studies of neonatal neuronal development in mammals have revealed that neuronal cell death following axotomy is apoptotic in nature. In adult animals, however, neuronal cell death following axonal injury may or may not exhibit features of apoptosis. Bcl-2 and Bax have been identified as inhibitor and promoter proteins, respectively, of apoptosis. To investigate the relationship between these proteins and neuronal cell death following axotomy in adult animals, we performed axotomy of the right hypoglossal nerve in adult male Wistar rats, and sacrificed the rats at various intervals after axotomy. We analyzed the expression of Bcl-2 and Bax immunohistochemically in the hypoglossal nuclei of the adult rats following axotomy. Our analysis showed an increase in the percentage of Bax-positive motoneurons relative to the total number of motoneurons in the hypoglossal nucleus on the axotomy side at three days after axotomy. In contrast, a low percentage of Bcl-2-positive motoneurons to the total number of motoneurons was noted at the same time interval after axotomy. Quantitative analysis of the signal intensity for Bcl-2 and Bax in individual neurons showed that Bax immunostaining significantly increased 7 days after axotomy, while the intensity of Bcl-2 immunostaining decreased in most of Bcl-2-positive neurons. Our results confirmed the occurrence of motoneuron cell death in adult rats after axotomy, and that a close temporal relationship exists between the reciprocal changes in Bcl-2/Bax expression and the loss of motoneurons. These results indicate the possible involvement of the Bcl-2/Bax system in the induction of neuronal cell apoptosis after axotomy in adult rats.

Age Factors↗

PubMed1991

Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43.

Neurons confined within the mammalian CNS usually do not regenerate after axonal injury, while axonal regeneration is the rule in the PNS. It has been hypothesized that this may be related to differences in the microenvironment of the PNS versus CNS and to differences in the neuronal response to injury. In order to test the latter hypothesis, we compared changes in gene expression after axotomy in two populations of neurons: rat facial motoneurons and rat rubrospinal neurons. In situ hybridization with cDNA probes for the medium and light neurofilament protein revealed a reduced mRNA content in both facial and rubrospinal neurons at all times investigated (i.e., 1, 2, and 3 weeks after axotomy). On the other hand, mRNAs for actin and tubulin were increased in both neuronal populations during the first week after axotomy. While this increase was sustained in facial motoneurons for several weeks, total tubulin mRNA and actin mRNA were decreased in rubrospinal neurons at 2 and 3 weeks after axotomy, coincident with their atrophy. The developmentally regulated T alpha 1 tubulin mRNA, which was previously shown to be reexpressed in facial motoneurons after axotomy, was elevated severalfold in axotomized rubrospinal neurons, and increased levels persisted in some rubrospinal neurons as late as 7 weeks after axotomy. Similarly, the developmentally regulated GAP-43 mRNA increased in both axotomized facial and rubrospinal neurons, and increased levels were sustained in some axotomized rubrospinal neurons for at least 7 weeks. The response of rubrospinal neurons to axotomy in the cervical spinal cord is, in the first week, qualitatively similar to the response of facial motoneurons. However, by 2 weeks after axotomy there is a generalized reduction in mRNA levels for all three cytoskeletal proteins that is associated with neuronal atrophy. During this period, mRNA levels for the two specific markers of the growth state, T alpha 1 tubulin and GAP-43, remain elevated. Thus, axotomy of rubrospinal neurons appears to set in motion two independent events. First, an axotomy signal initiates a cell-body reaction similar to that of PNS neurons, including increased mRNA levels for T alpha 1 tubulin and GAP-43. Later, a generalized cellular atrophy and decrease in mRNA levels occur without reversing the specific responses of T alpha 1 and GAP-43 to axotomy. We conclude that the failure of rubrospinal neurons to regenerate is not due to a failure to initiate gene-expression changes characteristic of regenerating peripheral neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed2001

Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death and elimination.

The timecourse of cell death in adult dorsal root ganglia after peripheral axotomy has not been fully characterised. It is not clear whether neuronal death begins within 1 week of axotomy or continues beyond 2 months after axotomy. Similarly, neither the timecourse of satellite cell death in the adult, nor the effect of nerve repair has been described. L4 and L5 dorsal root ganglia were harvested at 1-14 days, 1-6 months after sciatic nerve division in the adult rat, in accordance with the Animals (Scientific Procedures) Act 1986. In separate groups the nerve was repaired either immediately or following a 1-week delay, and the ganglia were harvested 2 weeks after the initial transection. Microwave permeabilisation and triple staining enabled combined TUNEL staining, morphological examination and neuron counting by the stereological optical dissector technique. TUNEL-positive neurons, exhibiting a range of morphologies, were seen at all timepoints (peak 25 cells/group 2 weeks after axotomy) in axotomised ganglia only. TUNEL-positive satellite cell numbers peaked 2 months after axotomy and were more numerous in axotomised than control ganglia. L4 control ganglia contained 13,983 (SD 568) neurons and L5, 16,285 (SD 1,313). Neuron loss was greater in L5 than L4 axotomised ganglia, began at 1 week (15%, P=0.045) post-axotomy, reached 35% at 2 months ( P<0.001) and was not significantly greater at 4 months or 6 months. Volume of axotomised ganglia fell to 19% of control by 6 months ( P<0.001). In animals that underwent nerve repair, both the number of TUNEL-positive neurons and neuron loss were reduced. Immediate repair was more protective than repair after a 1-week delay. Thus TUNEL positivity precedes actual neuron loss, reflecting the time taken to complete cell death and elimination. Neuronal death begins within 1 day of peripheral axotomy, the majority occurs within the first 2 months, and limited death is still occurring at 6 months. Neuronal death is modulated by peripheral nerve repair and by its timing after axotomy. Secondary satellite cell death also occurs, peaking 2 months after axotomy. These results provide a logical framework for future research into neuronal and satellite cell death within the dorsal root ganglia and provide further insight into the process of axotomy induced neuronal death.

Aging↗

PubMed2002

Brain-derived neurotrophic factor inhibits changes in soma-size of retinal ganglion cells following optic nerve axotomy in rats.

To determine if optic nerve axotomy affects the cell soma size of retinal ganglion cells and to establish whether such quantitative analysis is useful as a new way of evaluating retinal ganglion cell damage, we measured the changes in both the number and soma size of retinal ganglion cells after optic nerve axotomy in rats. Retinal ganglion cells were retrogradely labeled by fluoro-gold injection into the superior colliculus, and the soma size was measured using image-analysis software. We detected a decrease in the proportion of large-sized retinal ganglion cells that was significant at 3, 5 and 7 days after the axotomy, and an increased proportion of small-sized ones that was significant at 5 and 7 days after the axotomy, indicating that retinal ganglion cells shrank following axotomy, that there was a shift away from the largest category of retinal ganglion cells towards the smallest category. On days 3 and 5 post-axotomy, there was no significant change in the proportion of medium-sized retinal ganglion cells. Intravitreal injection of brain-derived neurotrophic factor one hour before the axotomy significant inhibited the increase in the proportion of small-sized retinal ganglion cells otherwise seen at 3 days after the axotomy. These results may suggest that larger retinal ganglion cells are more sensitive to optic nerve axotomy than small- and medium-sized ones, and that a quantitative analysis of soma size is a useful way of detecting retinal ganglion cell damage in the early phase after axotomy.

Animals↗

PubMed1990

Cell death of corticospinal neurons is induced by axotomy before but not after innervation of spinal targets.

The response of corticospinal neurons to axotomy at postnatal ages from 5 days to adulthood was studied in the golden hamster (Mesocricetus auratus). Corticospinal neurons were retrogradely labeled with fluorescent rhodamine latex beads injected into the cervical or lumbar spinal cord. A unilateral lesion of the medullary pyramidal tract was made 1-2 days later and the brains fixed 1-30 days after axotomy. Comparisons of labeled axotomized corticospinal neurons with labeled normal corticospinal neurons in the contralateral cortex showed that axotomy at 14 days or later caused cell shrinkage but not cell death. Axotomy prior to 14 days caused cell death of corticospinal neurons. More neurons died the earlier the lesion was made, culminating in virtual complete cell death of corticospinal neurons following axotomy at 5 days. Axotomy at a given age did not affect all corticospinal neurons uniformly. Lumbar projection neurons underwent cell death ranging from slight to complete following axotomy at 13 and 9 days, respectively. Cervical projection neurons, in contrast, survived axotomy after a lesion at 9 days but underwent complete cell death if the lesion occurred at 5 days. Since corticospinal axons innervate the cervical cord from postnatal days 4-8 and the lumbar cord from 10-14 days (Reh and Kalil, '81; J. Comp. Neurol. 200:55-67), the ability of corticospinal neurons to survive axotomy appears to be temporally well correlated with their innervation of spinal targets. These neurons die if their axons are cut prior to target innervation but are able to survive if axotomy occurs after their axons innervate spinal targets. The results show that plasticity in the corticospinal pathway documented in previous reports cannot take the form of regrowth of severed axons, since early lesions cause extensive corticospinal cell death. Aberrant corticospinal pathways resulting from early lesions must therefore arise from undamaged axons. Additional retrograde labeling experiments showed that the opposite cortex responded to contralateral pyramidotomy by sprouting into denervated areas of the spinal cord. Thus another source of plasticity after early pyramidal tract lesions is sprouting from corticospinal axons arising from the intact cortex.

Aging↗

PubMed1996

Interleukin-1 involvement in the induction of leukemia inhibitory factor mRNA expression following axotomy of sympathetic ganglia.

Axotomy of superior cervical (sympathetic) ganglia (SCG) results in increased neuropeptide gene expression. In vitro, neuropeptide gene expression is similarly increased by exposure to the inflammatory cytokine interleukin-1 (IL-1). The effect of IL-1 in-vitro has been shown to be mediated by leukemia inhibitory factor (LIF). Since IL-1 regulates neuropeptide expression via LIF in vitro, we asked whether axotomy in vivo produces an increase in LIF mRNA, and whether that increase is regulated by IL-1 activity. Within 6 h following axotomy, ganglionic LIF mRNA is substantially elevated. Moreover, axotomy produces a rapid and transient increase in intraganglionic IL-1 beta mRNA, followed rapidly by an increase in ICAM-1 mRNA, thereby suggesting a local source of IL-1 activity. Pretreatment with the anti-inflammatory agent dexamethasone (DEX) reduces the increases of both IL-1 beta and LIF mRNAs following axotomy. mRNA encoding the specific signal-transducing Type I IL-1 receptor is present in unlesioned SCG in vivo, and increases following axotomy. Local application of IL-1 beta in vivo induces LIF mRNA even in uninjured ganglia, though not to the extent seen with axotomy. DEX treatment blocks this IL-1 beta-mediated increase in LIF mRNA. Therefore, DEX blocks the induction of LIF mRNA by inhibiting both the production of IL-1 and its action on LIF gene expression. Axotomy of a homozygous IL-1 receptor type I gene knockout mouse leads to a delayed and/or diminished induction of LIF mRNA in SCG, but does not prevent LIF mRNA expression. We conclude that while IL-1 is likely to be involved in the cascade of gene expression that follows axotomy, it alone is not sufficient to mediate the full induction of LIF mRNA by axotomy.

Animals↗

PubMed1987

Effects of central or peripheral axotomy on membrane properties of sensory neurones in the petrosal ganglion of the cat.

1. The properties of sensory neurones in the petrosal ganglion of the cat were examined in vitro with intracellular electrodes 8 days after section of the central (bulbar roots) or peripheral process. Two types of cells, both with conduction velocities faster than 2 m/s and with humps on the falling phases of their action potentials (H-neurones), were studied: glossopharyngeal neurones arising from the tongue and pharynx, and carotid neurones originating in the carotid body and carotid sinus. 2. Peripheral axotomy produced an increase in action potential duration and a marked decrease in the amplitude and duration of the spike after-hyperpolarization in both glossopharyngeal and carotid neurones. 3. The maximum rate of depolarization of the action potential increased after peripheral axotomy in glossopharyngeal cells but did not change in carotid neurones. 4. The time-dependent inward rectification in response to hyperpolarizing pulses was markedly reduced in both types of cells after peripheral axotomy. 5. Section of the peripheral process produced a decrease of the rheobase of glossopharyngeal cells, but not of carotid neurones. After axotomy the proportion of cells giving tonic discharges in response to long depolarizing pulses increased from 13 to 54% among carotid neurones but did not change in glossopharyngeal cells. 6. No significant changes in membrane potential or input resistance of either group of cells were found after peripheral axotomy. 7. Central axotomy did not produce any changes in the electrophysiological properties of glossopharyngeal or carotid neurones. 8. Peripheral conduction velocity was decreased in both types of cells after peripheral axotomy, but did not change after section of the bulbar roots. 9. It is concluded that the electrical properties of sensory neurones are modified after peripheral axotomy but not after central axotomy. Furthermore, the changes produced by peripheral axotomy are different in neurones innervating different peripheral targets. 10. The possibility that some electrical properties of sensory neurones are maintained by their peripheral targets is discussed.

Action Potentials↗

PubMed1993

Changes in sodium and calcium channel activity following axotomy of B-cells in bullfrog sympathetic ganglion.

1. Currents mediated by Ca2+ channels using Ba2+ as a charge carrier (IBa), Na+ currents (INa) and voltage- and Ca(2+)-dependent K+ currents (IC) were recorded from bullfrog paravertebral sympathetic ganglion B-cells using whole-cell patch-clamp recording techniques. Currents recorded from control cells were compared with those from axotomized cells 13-15 days after transection of the postganglionic nerve. 2. Axotomy reduced peak IBa at -10 mV (holding potential = -80 mV) from 3.3 +/- 0.3 nA (n = 42) to 1.7 +/- 0.1 nA (n = 39, P < 0.001). Tail IBa at -40 mV following a step to +70 mV from a holding potential of -80 mV was also reduced in axotomized neurones (9.7 +/- 0.6 nA for forty-two control neurones and 5.2 +/- 0.3 nA for thirty-nine axotomized neurones; P < 0.001). Minimal changes were observed in the kinetics of activation and deactivation. 3. Pharmacological experiments using 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2- trifluoromethylphenyl)-pyridine-5-carboxylic acid methyl ester (BayK 8644), nifedipine and omega-conotoxin showed that axotomy predominantly affected the N-type Ca2+ channels which carry the majority of ICa in these neurones. L-type Ca2+ current was little affected and T-type Ca2+ currents were not observed in control or axotomized cells. 4. Development of inactivation of 0 mV and recovery from inactivation of IBa at -80 mV exhibited three distinct components in both control and axotomized neurones: 'fast', 'intermediate' and 'slow'. The relative proportions of both the 'fast' and 'intermediate' components of inactivation at 0 mV were almost doubled after axotomy (fast component was 15% in control and 29% in axotomized neurones; intermediate component was 17% in control and 26% in axotomized neurones). 'Fast' and 'intermediate' inactivation tended to develop more rapidly and recover more slowly after axotomy. The rate of onset of 'slow' inactivation was unaffected by axotomy but the steady-state level at -40 mV was increased. Most of the change in IBa properties may be secondary to enhanced inactivation associated with axotomy. 5. Axotomy reduced IC (measured at the end of a 3 ms step from -40 to +20 mV) from 34.5 +/- 4.9 (n = 26) to 19.2 +/- 1.5 nA (n = 49, P < 0.005). This reduction may be secondary to the reduction in calcium channels available for activation from -40 mV following axotomy. 6. The TTX-sensitive and TTX-insensitive components of peak Na+ conductance (GNa) were both increased after axotomy. Total GNa was increased from 184.9 +/- 8.4 to 315.2 +/- 16.4 nS (n = 37 for both P < 0.001). Most of the kinetic and steady-state properties of INa were unchanged after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

[The expression of BDNF and NT-3 in dorsal root ganglion following peripheral and central axotomy--an immunohistochemical study].

OBJECTIVE: To explore the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3(NT-3) in dorsal root ganglion (DRG) following peripheral and central axotomy. METHODS: Fifteen male adult cats were divided into intact group, peripheral axotomy group and central axotomy group. The ten cats of the latter two groups were subjected to unilateral peripheral cut and central processes cut respectively. The animals were allowed to survive 4 days long; L5 DRG was taken from each animal and made into frozen sections 20 microns thick. The sections were stained using antisera of BDNF and NT-3 respectively by immunohistchemical ABC method. The neuronal numbers of BDNF and NT-3 of the three groups were counted and compared. RESULTS: The positive products of BDNF were mainly distributed in small to medium sized neurons (13-57 microns) while those of NT-3 were mainly in large sized neurons (57-100 microns). The neuronal numbers of BDNF and NT-3 in peripheral and central axotomy groups (24.1 +/- 3.5, 29.4 +/- 5.2; 19.4 +/- 2.4, 20.2 +/- 1.9) increased significantly than those of intact group (12.1 +/- 2.2, 13.3 +/- 2.9), P < 0.01. And the neuronal numbers of BDNF and NT-3 in peripheral axotomy groups were more than those of central axotomy group(P < 0.05). CONCLUSION: The results indicate that peripheral axotomy and central axotomy lead to the increase of the expression of BDNF and NT-3 in DRG neurons. And the effect of peripheral axotomy is greater than that of central axotomy.

Animals↗

PubMed2006

Proximity of lesioning determines response of facial motoneurons to peripheral axotomy.

We recently found that rubrospinal (RS) neurons, which typify central neurons projecting within the central nervous system (CNS), exhibited different neuronal and glial reactions to axotomy at proximal as opposed to distal sites. To determine whether distance also determines the reaction to axonal injury of central neurons projecting to the periphery, we studied the temporal expression of four free-radical-related enzymes as well as the severity of cell loss, perineuronal astrocytic and microglial reactions, and degeneration of the proximal central axons of facial motoneurons after axotomies performed at various sites on the brainstem surface and in the stylomastoid foramen, respectively. Distal lesions resulted in upregulation of these neurons' expression of nitric oxide synthase (NOS) and persistent downregulation of their expression of the NOS-activating enzyme calcineurin. It also led to transient upregulation of their expression of manganese-dependent superoxide dismutase (Mn-SOD), and resulted in a mild neuronal loss. Proximal axotomy led to an upregulation of NOS but a transient downregulation in the expression of calcineurin and Mn-SOD at 4 weeks after injury. This was accompanied by severe cell loss and swelling of mitochondria at 2-4 weeks postinjury. However, neither proximal nor distal axonal lesioning led to nuclear fragmentation or TUNEL staining of neurons. Proximal as opposed to distal axotomy produced an earlier transformation of glial morphology, including the hypertrophy of astrocytic processes and metamorphosis of ramified microglia to amoeboid cells. We unexpectedly found that unlike RS neurons, whose central axons degenerated slowly and in an anterograde manner only after the severe cell loss induced by proximal axotomy, the central axons of facial motoneurons degenerated rapidly and in a retrograde manner independently of the severity of loss of these neurons after axotomy. However, degeneration began sooner after proximal than after distal axotomy. Since the central axons of both rubrospinal neurons and facial motoneurons lie within the CNS, the differences in whether and how they degenerated after axotomy suggests that central neurons that project within and outside the CNS are inherently different. The significance of these and also the free radical environment regulation differences between these two types of neurons following close and distant axotomies remains to be explored.

Animals↗

PubMed1991

Axotomy alters putative neurotransmitters in visceral sensory neurons of the nodose and petrosal ganglia.

Acute peripheral axotomy of the visceral sensory neurons of the vagus and glossopharyngeal nerves removes peripheral depolarizing and trophic influences to their sensory ganglia. To study axotomy-induced changes in the putative neurotransmitters of visceral sensory neurons, rats were sacrificed 1, 3, 7 or 14 days after transection of either the cervical vagus and superior laryngeal nerves (to affect peripheral axotomy of the nodose ganglion) or the glossopharyngeal and carotid sinus nerves (to affect peripheral axotomy of the petrosal ganglion). The numbers of tyrosine hydroxylase (TH)-immunoreactive (ir), vasoactive intestinal peptide (VIP)-ir, calcitonin-gene-related peptide (CGRP)-ir, and substance P (SP)-ir neurons in the respective ganglia were analyzed in axotomized and control ganglia. In the nodose ganglion, axotomy of the cervical vagus resulted in a rapid (by 1 day) reduction in the number of TH-ir cells, whereas VIP-ir neurons were dramatically increased in number by 3 days. CGRP- and SP-ir cells in the nodose ganglion were relatively unaffected by axotomy. In the petrosal ganglion, axotomy of the glossopharyngeal and carotid sinus nerves greatly reduced the number of TH-ir cells but did not alter the number VIP-ir neurons. CGRP- and SP-ir neurons in the petrosal ganglion were reduced in number by axotomy. Thus, axotomy of visceral sensory neurons differentially changed the content and perhaps the expression of putative transmitters. Differential changes were seen among transmitters in a single ganglia and between ganglia. These data demonstrate the plasticity of putative neurotransmitter systems in visceral afferent systems of adult rats.

Animals↗

PubMed1994

Naturally occurring and axotomy-induced motoneuron death and its prevention by neurotrophic agents: a comparison between chick and mouse.

Neuronal cell death is an important regressive event during the normal development of the peripheral and central nervous systems of many vertebrate and invertebrate species. Furthermore, when neurons are deprived of their target following axonal injury (axotomy) during embryonic, fetal, or early postnatal development, they undergo massive cell death. Both naturally occurring and axotomy-induced neuronal cell death can be prevented by treatment with growth factors or neurotrophic agents. Naturally occurring cell death of spinal MNs has been extensively studied in both avians and mammals. However, compared with mammals, there is little information on the effects of axotomy in avian species and it is not known whether trophic agents can modify axotomy-induced death in avian MNs. It is also not known whether trophic/growth factors can promote the in vivo survival of mammalian MNs during the period of naturally occurring cell death. We have examined (1) the time course of axotomy-induced death of lumbar spinal MNs in chick and mouse, and (2) the survival-promoting activity of a number of previously characterized growth and trophic factors on both programmed and axotomy-induced MN death in these two species. We show that axotomy performed on, or prior to, E12 in the chick results in a rapid decrease (i.e. 50%) in MN numbers within 3-4 days postsurgery, whereas these cells were able to survive for up to 1 week following axotomy on E14. By contrast, mouse MNs remained vulnerable to axotomy for at least 5 days after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

The effects of remaining axons on motoneuron survival and NOS expression following axotomy in the adult rat.

it is well known that target removal or distal axotomy in adult animals results in no detectable loss of motoneurons in the spinal cord. By performing axotomy in the seventh cervical (C7) spinal nerve at different distances from the spinal cord (0, 2, 4, 8 mm respectively), this study examines the effects of the remaining axons on motoneuron survival as well as NOS expression. Results of the present study show that axotomy in adult peripheral nerve can induce significant spinal motoneuron death if axotomy is performed close enough to the spinal cord. The closer the axotomy to the spinal cord, the higher the rate of motoneuron loss was observed. The most significant motoneuron loss was found in animals with axotomy at 0 mm to the cord, which was coincident with the highest percent of NOS-positive motoneurons. The rate of survival of motoneurons increases and the percent of NOS-positive motoneurons decreases when the distance of the axotomy to the cord increases from 0 to 4 mm. No significant motoneuron loss nor NOS-positive motoneurons were observed when axotomy was performed at 4 mm and distally. These results indicate that the survival of spinal motoneurons in adult rat following axotomy is largely dependent on the length of the remaining axons. The longer the remaining axon, the better for motoneuron survival. The minimal length of axon for motoneuron survival in adult rat seems to be at least 4 mm.

Animals↗