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PubMed1998

Axotomy-induced c-JUN expression in young medial septal neurons is regulated by nerve growth factor.

In the present study we investigated the axotomy-induced expression of the proto-oncogene c-jun in young rat medial septal neurons and its regulation by nerve growth factor. First, medial septal neurons were retrogradely labelled by Fast Blue injection into the hippocampus at postnatal day 1 (P1). Rats of different developmental ages (P6, P9, P14, P21, P28 and P42) were then subjected to bilateral fimbria-fornix transection resulting in the axotomy of septohippocampal projection neurons. After the lesion, c-JUN immunoreactivity was observed in the nuclei of axotomized medial septal neurons of all stages examined, suggesting that c-JUN induction is an age-independent feature of axotomized medial septal neurons. Double immunolabelling for choline acetyltransferase and c-JUN or parvalbumin and c-JUN, respectively, revealed that both cholinergic and GABAergic septohippocampal projection neurons express c-JUN after axotomy. In addition, a co-localization of immunostaining for c-JUN and the neuropeptide galanin was found after lesion, as both proteins were induced in the same medial septal neurons following fimbria-fornix transection. Next, the regulation of c-JUN expression in axotomized medial septal neurons was studied in organotypic cultures of the medial septum. Axotomized medial septal neurons in culture did not express c-JUN in contrast to the in vivo situation. With the concept that nerve growth factor suppresses c-JUN expression, slice cultures of the medial septum were treated with antibodies against nerve growth factor. This treatment caused a dose-dependent increase in c-JUN-positive cells in these slice cultures. Simultaneous addition of nerve growth factor and antibodies against nerve growth factor resulted in the reversal of this effect. These data suggest an age-independent induction of c-JUN in axotomized medial septal neurons and its regulation by nerve growth factor.

Acetylcholine↗
PubMed2000

Differential taurine effect on outgrowth from goldfish retinal ganglion cells after optic crush or axotomy. Influence of the optic tectum.

The interaction between innervated tissues, targets and nerves is crucial in the maintenance of physiological conditions, and the disturbance of this harmony causes the production of morphological and biochemical changes. After lesion of the optic nerve, several modifications take place in the retina, the optic tectum and the optic nerve. The influence of the tectum on the outgrowth from the goldfish retina and the possible role of taurine was studied. Ganglion retinal cells were identified by retrolabeling with Dil. Crushing the optic nerve 10 days prior to plating retinal cells, as compared with optic axotomy, did not affect the survival of cultured retinal cells, as well as the length of the neurites. However, the number of neurites per cell and the branching of the longest fiber were higher after axotomy than after crushing. The addition of taurine to the medium did not modify this response at 5 days in culture. At early periods in culture, the stimulatory effect on isolated ganglion cell outgrowth produced by taurine was enhanced after axotomy respecting crushing of the optic nerve, but was not affected in retinal explants. The addition of medium from cultured optic tectum several days post-crush of the optic nerve to retinal explants from intact retinas or coming from post-crush retina modified the outgrowth, being inhibitory or stimulatory in a time-dependent manner. The co-culture of optic tectum and retina also affected the outgrowth from the retina with a byphasic shape. The results support the differential response of the retina facing partial or complete interruption with the target and limit the effect of taurine to early periods in culture. In addition, the production of inhibitory factors from the tectum, plus the stimulatory ones, are strongly supported by this work.

Animals↗
PubMed1999

Axotomy results in major changes in BDNF expression by dorsal root ganglion cells: BDNF expression in large trkB and trkC cells, in pericellular baskets, and in projections to deep dorsal horn and dorsal column nuclei.

Brain derived neurotrophic factor (BDNF) is normally expressed by a small number of predominantly trkA-expressing dorsal root ganglion cells. Using immunocytochemistry and in situ hybridization, we have examined the effect of sciatic nerve section on the expression of BDNF in the adult rat. Following axotomy there was a long lasting (4-week) increase in BDNF mRNA and protein in large-diameter, trkB- and trkC-expressing dorsal root ganglion cells. By 2 days postaxotomy, expression of BDNF mRNA had increased from 2% of trkB cells to 50%, and from 18% of trkC cells to 56%. In contrast, BDNF expression in most trkA cells was unchanged, although was increased in the small population of medium- and large-sized trkA cells. Following axotomy, BDNF-immunoreactive terminals appeared in the central axonal projections of large-diameter cells, including the deep dorsal horn and gracile nucleus. Neuropeptide Y was also upregulated following axotomy and was coexpressed with BDNF in the cell bodies and central terminals of the large cells. Ultrastructural analysis in lamina IV of the spinal cord revealed that BDNF terminals in these central projections establish synaptic contacts. Immunoreactivity at 4 weeks was also observed in pericellular baskets that contained calcitonin gene-related peptide (CGRP) and surrounded trkA- and trkB-expressing cells in L4 and L5 lumbar ganglia. These baskets are likely to arise from local, highly immunoreactive, BDNF/CGRP/trkA-expressing cells. Our results identify several novel targets for BDNF and imply that it acts locally in both autocrine and paracrine modes, as well as centrally in a synaptic mode, to modulate the response of somatosensory pathways in nerve injury.

Afferent Pathways↗
PubMed1999

Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve axotomy model.

Recent studies have shown that hepatocyte growth factor (HGF) promotes the survival of embryonic motor neurons. However, it remains unclear whether HGF has trophic effects on mature motor neurons. In the present study, we examined the effects of HGF on adult motoneurons using the hypoglossal nerve transection model. In adult rats, neurons in the hypoglossal nucleus show a dramatic loss of choline acetyltransferase (ChAT) protein and mRNA after the axotomy. This reduction of ChAT was markedly prevented when HGF was administered continuously at the cut end of the nerve using an osmotic pump. The HGF receptor, c-met, protein and mRNA, which were faintly expressed in hypoglossal neurons under normal conditions, gradually increased and reached maximal levels 2 weeks after the axotomy. Administration of HGF reduced this c-met upregulation almost to normal levels. We also quantified HGF mRNA in the tongue and hypoglossal nucleus. The tongue contained abundant HGF mRNA, whereas the nucleus contained only low levels. Interestingly, the HGF mRNA level in the nucleus did not increase after the axotomy. These findings suggest that HGF is principally produced in the tongue and contributes to maintain ChAT expression in the nucleus. HGF produced in the hypoglossal nucleus alone after disconnection from the tongue may not be sufficient for the maintenance of the motor neuron function. Thus, exogenously applied HGF was effective to prevent the downregulation of ChAT activities. These findings provide a strong rationale for the potential clinical use of HGF for the treatment of motor neuron degenerative disease.

Animals↗
PubMed2001

Role of GAP-43 in mediating the responsiveness of cerebellar and precerebellar neurons to axotomy.

To determine whether the competence for axonal sprouting and/or regeneration in the cerebellar system correlates with GAP-43 expression, we have studied GAP-43 mRNA and protein expression in the postlesioned cerebellum and inferior olive. Purkinje cells transiently express GAP-43 during their developmental phase (from E15 to P5 in the rat) which consists of fast axonal growth and the formation of the corticonuclear projection. Adult Purkinje cells, which in control adult rats do not express GAP-43, are extremely resistant to the effects of axotomy but cannot regenerate axons. However, a late and protracted sprouting of axotomized Purkinje cells occurs spontaneously and correlates with a mild expression of GAP-43 mRNA. In contrast, inferior olivary neurons, despite their high constitutive expression of GAP-43, do not sprout but retract their axons and die after axotomy. Furthermore, mature Purkinje cells in cerebellar explants of transgenic mice that overexpress GAP-43 do not regenerate after axotomy, even in the presence of a permissive substrate (cerebellar embryonic tissue) and, contrary to the case in wild-type mice, they do not survive in the in vitro conditions and undergo massive cell death. These results show that the expression of GAP-43 is not only associated with axonal growth, but also with neuronal death.

Afferent Pathways↗
PubMed2004

c-Jun N-terminal kinase 3 deficiency protects neurons from axotomy-induced death in vivo through mechanisms independent of c-Jun phosphorylation.

Both the transcription factor c-Jun and the c-Jun N-terminal kinases (JNKs) have been associated with neuronal loss in several death paradigms. JNK are key regulators of c-Jun and a common accepted model has been that JNKs mediate neuronal death through modulation of c-Jun activation. In the present study, we examined whether JNK2 and -3 (JNK members most associated with neuronal loss) deficiency can rescue neuronal loss caused by facial and sciatic nerve axotomy in the neonate in vivo. JNK2, JNK3, and JNK2/3 double-deficient neurons displayed significantly less death in the facial nerves of the CNS when compared with controls. JNK2 and JNK2/3 double-deficient animals also showed reduced c-Jun phosphorylation and induction following axotomy, consistent with the model that JNK acts to regulate death by activating c-Jun. Of significance, however, protection of facial nerves in JNK3-deficient animals was not accompanied by reduction in c-Jun activation. These results suggest that JNKs can mediate death independently of c-Jun. Importantly, the lack of correlation between JNK3 deficiency and c-Jun induction was not universal. In a sciatic axotomy model of neuronal injury in the neonate, death of DRG neurons was also reduced by JNK3 deficiency. However, in this case, c-Jun activation was also eliminated.

Animals↗
PubMed1998

The characteristics of the electrovomeronasogram: its loss following vomeronasal axotomy in the garter snake.

Electrovomeronasogram (EVG) recordings were made from adult garter snakes, Thamnophis sirtalis. Stimulation of vomeronasal epithelium with a stimulus prepared from prey, earthworm electric shock secretion (ESS), evoked EVG response in a dose-dependent manner. The magnitude of the EVG response to ESS was remarkably larger than n-amyl acetate and glutamate, which elicited insignificant responses, supporting the idea that the vomeronasal system is differentially sensitive to liquid delivery of biologically significant chemical stimuli. Fourteen days following vomeronasal axotomy, the magnitudes of the EVG responses of animals which received bilateral axotomy without cauterization or with cauterization was -0.19+/-0.07 mV or -0.05+/-0.02 mV respectively, compared with the normal EVG response of -0.41+/-0.10 mV. The epithelia of animals which received bilateral axotomy without cauterization exhibited remarkable degeneration of the bipolar neurons. Maximal depletion of bipolar neurons occurred in the epithelia denervated with cauterization, though the difference between cell densities in vomeronasal neuron layers in these epithelia was not statistically significant. The present results clearly indicate that the fewer neurons the epithelium contains, the smaller EVG response it generates, suggesting that the receptor neurons are the primary origin of EVG responses.

Animals↗
PubMed1999

Depletion of GDNF from primary afferents in adult rat dorsal horn following peripheral axotomy.

Glial cell line-derived neurotrophic factor (GDNF) is produced in a subset of adult rat spinal ganglion neurons and anterogradely transported to the superficial dorsal horn. In this study the effect of sciatic nerve axotomy on the expression of GDNF protein in the dorsal horn was investigated, using immunocytochemistry. Image analysis showed a 44% decrease relative to the non-transected side after 5 days survival, progressing to more than 80% decrease after 10 days and remaining so for at least 100 days. This rapid and strong decrease suggests active down-regulation of GDNF protein after peripheral axotomy. The observed down-regulation of GDNF is compared with changes observed for other substances in primary afferents after peripheral axotomy and is discussed in light of its presumed trophic or transmitter role in nociception.

Animals↗
PubMed2001

Bcl-2 is not required in retinal ganglion cells surviving optic nerve axotomy.

Axotomy of the optic nerve in rodents induces the majority of retinal ganglion cells (RGCs) to undergo apoptosis: Only 10-15% survive 14 days past lesion. The molecular mechanism allowing this survival is not known. To test whether expression of the anti-apoptotic proto-oncogene bcl-2 gene is required in those RGCs, we examined the effect of optic nerve axotomy in bcl-2-/- mice. 7 days and 14 days post-lesion, the same number of surviving RGCs was detected in mutant and wild type retinas. Thus, the bcl-2 gene is not necessary for the survival of the subpopulation of retinal ganglion cells resisting axotomy-induced apoptosis in adult mice, nor does its normal expression delay retinal ganglion cell degeneration.

Animals↗
PubMed1997

GDNF is a trophic factor for adult rat corticospinal neurons and promotes their long-term survival after axotomy in vivo.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for several neuronal populations involved in motor control. The present study evaluates the trophic actions of GDNF on corticospinal neurons, an important central nervous system motor projection into the spinal cord. Death of spinal motoneurons and corticospinal neurons is observed in the neurodegenerative disease amyotrophic lateral sclerosis. Axotomy of adult rat corticospinal neurons at internal capsule levels induces half of them to die, and the surviving population displays severe atrophy. To examine the trophic effects of GDNF on corticospinal neurons, Fast Blue-labelled corticospinal neurons were stereotaxically axotomized at internal capsule levels and GDNF was infused intracortically to lesioned corticospinal neurons at total doses of 2, 4, 10, 20, 40, 100 and 300 microg for 7 days. GDNF prevented axotomy-induced death of corticospinal neurons at doses between 2 and 40 microg and abolished or attenuated their atrophy at all doses examined. In addition, treatment with 8 microg GDNF for the first 2 weeks after axotomy resulted in the long-term survival of corticospinal neurons for 42 days. With regard to the development of treatment strategies for upper motoneuron degeneration in amyotrophic lateral sclerosis, application of GDNF via the cerebrospinal fluid may be more relevant than intracortical delivery as its diffusion within the brain parenchyma is limited. Intraventricular as well as intracisternal infusion of GDNF (300 microg over 7 days) completely prevented corticospinal neuron death. These results show that GDNF promotes the long-term survival of corticospinal neurons and has a positive effect on their size in vivo. Furthermore, the survival-promoting effect of GDNF on corticospinal neurons after delivery via cerebrospinal fluid has important clinical implications for potential treatment of the upper motoneuron degeneration seen in amyotrophic lateral sclerosis.

Animals↗
PubMed1998

Regulation of expression of galanin and galanin receptors in dorsal root ganglia and spinal cord after axotomy and inflammation.

Galanin can normally be detected only in a few dorsal root ganglion (DRG) neurons, but it is dramatically upregulated after peripheral nerve injury in both rat and monkey. Galanin is stored in large dense core vesicles, which after axotomy are often found close to the membrane of afferent nerve endings in the dorsal horn. In the monkey there is an increase in galanin in many nerve terminals in the superficial dorsal horn after axotomy, but such an increase is more difficult to detect in the rat. Galanin is also present in local dorsal horn neurons, where it is upregulated by peripheral inflammation. Both galanin-R1 and galanin-R2 receptor mRNAs are expressed in rat DRGs, mainly in, respectively, large and small DRG neurons. Galanin-R1 receptor mRNA is downregulated in DRG neurons after axotomy, and a small decrease in galanin-R2 receptor mRNA levels can also be seen. After peripheral tissue inflammation galanin-R1 receptor mRNA levels decrease and galanin-R2 receptor mRNA levels increase. The present results show that galanin and galanin receptors are present in sensory and local dorsal horn neurons and are regulated by nerve injury and inflammation. Galanin may therefore be involved in processing of pain information, primarily exerting analgesic effects. Whereas local dorsal horn neurons represent a defense system against inflammatory pain, we have proposed that a second defense system, against neuropathic pain, is intrinsic to DRG neurons.

Animals↗
PubMed2006

Synaptic and somatic effects of axotomy in the intact, innervated rat sympathetic neuron.

A biophysical description of the axotomized rat sympathetic neuron is reported, obtained by the two-electrode voltage-clamp technique in mature, intact superior cervical ganglia in vitro. Multiple aspects of neuron functioning were tested. Synaptic conductance activated by the whole presynaptic input decreased to 29% of the control value (0.92 muS per neuron) 1 day after axotomy and to 18% after 3 days. Despite the decrease in amplitude of the macroscopic current, miniature excitatory postsynaptic current (mEPSC) mean conductance, acetylcholine (ACh) equilibrium potential, and EPSC decay time constant were unaffected. Synaptic efficacy was tested during paired-pulse or maintained stimulation (5, 10, and 15 Hz, 10-s duration). Quantal release in axotomized neurons was preserved during the tetanus despite the reduction of the initial EPSC amplitude, suggesting that ACh secretion depended on the number of surviving synapses; each of them exhibited dynamic behavior during trains similar to that of normal synapses. Facilitation of EPSC amplitude was noted in 2-day axotomized neurons during the first few impulses in the train. Voltage-dependent potassium currents (the delayed I(KD) and the transient I(A)) exhibited an early drastic decrease in peak amplitude; these effects persisted 7 days after axotomy. Marked changes in I(A) kinetics occurred after injury: the steady-state inactivation curve shifted by up to +17 mV toward positive potentials and the voltage sensitivity of inactivation removal became steeper. I(A) impairment was reflected in a reduced inward threshold charge for discharge and reduced spike repolarization rate. Synaptic and somatic data were applied in a mathematical model to describe the progressive decrease in the safety factor, and the eventual failure of ganglionic transmission after axotomy.

Animals↗
PubMed2006

Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion.

PURPOSE: Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. The time course of cell death is variable and depends in part on the degree of injury sustained. Decreasing reactive oxygen species (ROS) levels or shifting the redox state to reduction promotes the survival of RGCs in tissue culture after axotomy. It was hypothesized that a specific ROS, superoxide anion, acts as an intracellular signaling molecule for RGC death after axotomy. METHODS: Intracellular superoxide levels were measured after dissociation in retrograde-labeled rat RGCs with use of the superoxide-sensitive fluorophores hydroethidium and MitoSOX Red. Having found a significant increase, the effect of axotomy was determined on superoxide levels independent of dissociation with an optic nerve crush model. RESULTS: Optic nerve crush caused RGCs to undergo a superoxide burst. The burst was asynchronous and was manifested in only a fraction of cells at any given time. Neurotrophin deprivation was not responsible for the superoxide burst because it was not prevented by incubation with the neurotrophic factors brain-derived neurotrophic factor, ciliary neurotrophic factor, forskolin, or insulin. Several inhibitors of intracellular superoxide generation were studied, but only antimycin A, which inhibits complex III of the mitochondrial electron transport chain, blocked the increase in superoxide. CONCLUSIONS: These findings suggest that superoxide generated in the mitochondrial electron transport chain could be a parallel system to neurotrophic deprivation for signaling cell death after axonal injury.

Animals↗
PubMed2006

Synaptogenesis regulates axotomy-induced activation of c-Jun-activator protein-1 transcription.

The activator protein-1 (AP1) transcription complex remains active for long periods after axotomy, but its activity diminishes during target contact. This raises the possibility that the function of this complex is regulated by the synaptic connections. Using Aplysia californica, we found that crushing peripheral nerves in vivo enhanced AP1 binding in the sensory neurons that lasted for weeks and then declined as regeneration was completed. The AP1 complex in Aplysia is a c-Jun homodimer. Its activation, after axotomy, is mediated by Aplysia c-Jun-N-terminal kinase (apJNK), which enters the nucleus of sensory neurons and phosphorylates c-Jun at Ser-73 (p73-c-Jun). Active AP1 in the sensory neurons did not mediate apoptosis and was not involved in the appearance of the long-term hyperexcitability that develops in these cells after axotomy, and blocking the activation of apJNK in vitro did not influence neurite outgrowth. In contrast, the levels of activated apJNK and p73-c-Jun declined markedly when sensory neurons formed synapses with motor neuron L7 in vitro. Furthermore, inhibiting the pathway accelerated synaptogenesis between sensory neurons and L7. These data suggest that positive and negative modulation of the JNK-c-Jun-AP1 pathway functions in alerting the nucleus to the loss and gain of synapses, respectively.

Animals↗
PubMed2000

Ultrastructural evidence for a preferential elimination of glutamate-immunoreactive synaptic terminals from spinal motoneurons after intramedullary axotomy.

After axotomy in the ventral funiculus of the cat spinal cord, about half of the population of lesioned motoneurons die at 1-3 weeks postoperatively, whereas the other half survives and generates new axons through the lesion area. To identify conditions that may promote survival and regeneration of motoneurons subjected to this kind of injury, the authors examined ultrastructurally lesion-induced changes in the number and distribution of nerve terminals on the somata and proximal dendrites of alpha-motoneurons in the 7th lumbar spinal segment (L7) of the cat spinal cord. Intramedullary axotomy resulted in a profound reduction in the number of nerve terminals impinging on the somata and proximal dendrites, with the maximal effect seen at 3 weeks postlesion. At that time, only 12-25% of the normal number of terminals remained on the cell somata, and 22-33% remained on proximal dendrites. Thereafter, a gradual increase in terminal numbers occurred, reaching normal levels at 34 weeks after the lesion. Already at 2 days postoperatively and, most obviously, at 3 weeks postoperatively, type S nerve terminals were eliminated to a larger degree than type F terminals. Postembedding immunohistochemistry confirmed that the largest reduction at 3 weeks was seen for excitatory glutamate-immunopositive type S nerve terminals (90%), whereas inhibitory glycine-immunoreactive and gamma-aminobutyric acid (GABA)-immunoreactive type F terminals were affected less (70% reduction). This led to a distinct shift in the ratio between the numbers of terminals that were immunopositive for glycine and GABA and the numbers of terminals that were labeled for glutamate. For the cell body, this ratio increased from 3.7 in normal material to 14.5 in lesioned motoneurons, whereas the corresponding values for proximal dendrites were 3.8 and 7.5. The preferential elimination of glutamatergic inputs to lesioned motoneurons may reflect an active reorganization of the synaptic input to diminish the excitotoxic influence on these neurons, thereby promoting the survival of motoneurons after intramedullary axotomy.

Animals↗
PubMed2000

Axonal regeneration of retinal ganglion cells depending on the distance of axotomy in adult hamsters.

PURPOSE: To examine the relationship between the distance of axotomy and axonal regeneration of injured retinal ganglion cells (RGCs) systematically and the effect of a predegenerated (pretransected or precrushed) peripheral nerve (PN) graft on axonal regeneration of RGCs axotomized at a definite distance (0.5 mm from the optic disc) in comparison with a normal PN graft. METHODS: The optic nerve (ON) was transected intraorbitally at 0.5, 1, 1.5, 2, or 3 mm or intracranially at 6 to 8 mm from the optic disc, and a PN graft was transplanted onto the ocular ON stump in adult hamsters. Four weeks after grafting, the number of RGCs regenerating their injured axons into the PN graft was investigated in all animals. RESULTS: The number of regenerating RGCs decreased significantly when the distance of axotomy increased from 0.5 to 7 mm. A precrushed PN graft was shown to enhance more injured RGCs to regenerate axons than a normal or pretransected PN graft. CONCLUSIONS: The distance of axotomy on the ON of adult hamsters is critical in determining the number of regenerating RGCs. Thus, experimental strategies to repair the damaged ON by PN transplantation is to attach a precrushed PN graft as close to the optic disc as possible to obtain optimal axonal regeneration of the axotomized RGCs.

Animals↗
PubMed2001

Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons.

Axonal transection of adult sympathetic and sensory neurons leads to a decrease in their content of target-derived nerve growth factor (NGF) and to dramatic changes in the expression of several neuropeptides and enzymes involved in transmitter biosynthesis. For example, axotomy of sympathetic neurons in the superior cervical ganglion (SCG) dramatically increases levels of galanin, vasoactive intestinal peptide (VIP), and substance P and their respective mRNAs and decreases mRNA levels for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Axotomy of sensory neurons in lumbar dorsal root ganglia (DRG) increases protein and mRNA levels for galanin and VIP and decreases levels for substance P and calcitonin gene-related peptide (CGRP). To assess whether reduction in the availability of endogenous NGF might play an important role in triggering these changes, we injected nonoperated animals with an antiserum against NGF (alphaNGF). alphaNGF increased levels of peptide and mRNA for galanin and VIP in neurons in both the SCG and DRG. NPY protein and mRNA were decreased in the SCG, but levels of TH protein and mRNA remained unchanged. In sensory neurons the levels of SP and CGRP protein decreased after alphaNGF treatment. These data suggest that the reduction in levels of NGF in sympathetic and sensory neurons after axotomy is partly responsible for the subsequent changes in neuropeptide expression. Thus, the peptide phenotype of these axotomized neurons is regulated both by the induction of an "injury factor," leukemia inhibitory factor, as shown previously, and by the reduction in a target-derived growth factor.

Animals↗
PubMed2002

Neither axotomy nor target-tissue inflammation changes the NOS- or VIP-synthesis rate in distal bowel-projecting neurons of the porcine inferior mesenteric ganglion (IMG).

The present study was aimed at disclosing axotomy- and inflammation-induced changes in the chemical coding of retrogradely labelled distal bowel-projecting neurons in the porcine IMG. Particular attention was paid to the changes in the expression pattern of vasoactive intestinal polypeptide and nitric oxide synthase (as a marker of nitric oxide) in affected cells, as these substances are thought to play a crucial role in the regeneration of injured sympathetic neurons. However, while both pathological processes failed to induce an increase in the number of sympathetic bowel-projecting neurons exhibiting vasoactive intestinal polypeptide or nitric oxide synthase, axotomy, but not target-tissue inflammation, led to the upregulation in the expression pattern of galanin, pituitary adenylate cyclase-activating peptide and/or Leu5-enkephalin in the affected perikarya. On the other hand, axotomy resulted in a diminished density of vasoactive intestinal polypeptide-immunoreactive intraganglionic nerve fibres, whilst target-tissue inflammation evoked a distinct increase in the number of visible vasoactive intestinal polypeptide-immunoreactive terminals, especially in those regions where bowel-projecting neurons were located. Thus, the data obtained in the present study run counter to the results of the injury-related responses observed in neurons of the sympathetic chain ganglia, suggesting the existence of either species- or target tissue-dependent differences in the injury-induced responses of the affected sympathetic neurons.

Animals↗