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PubMed1998

Characterization of spinal motoneuron degeneration following different types of peripheral nerve injury in neonatal and adult mice.

Experimental lesions have been used widely to induce motoneuron (MN) degeneration as a model to test the ability of different trophic molecules to prevent lesion-induced alterations. However, the morphological mechanisms of spinal MN death following different types of lesions is not clear at the present time. In this study, we have characterized the morphological characteristics of MN cell death by examining DNA fragmentation and the ultrastructural and light microscopic morphological features of MNs following different types of spinal nerve injury (i.e., axotomy and avulsion) in the developing and adult mouse. In neonatal mice, axotomy induced cell death as well as the atrophy of MNs that survived the injury. DNA fragmentation could be detected by using the terminal deoxynucleotidyl transferase (TUNEL) method during the cell death process following neonatal axotomy, whereas TUNEL labeling was not observed following either neonatal or adult avulsion. However, with the exception of TUNEL labeling, the morphological characteristics of MN death following neonatal axotomy and avulsion were similar, and both resembled most closely the form of programmed cell death termed cytoplasmic or type 3B, which exhibits similarities as well as differences with currently accepted definitions of apoptosis. By contrast, adult avulsion resulted in a type of degeneration that resembled necrosis more closely. However, even there, the morphology was mixed, showing characteristics of both apoptosis and necrosis. These results indicate that the mode of MN degeneration is complex and is related to developmental age and type of lesion.

Animals↗
PubMed1981

Regional specialization of the chick retina as revealed by the size and density of neurons in the ganglion cell layer.

On the basis of both morphological criteria and survival after ganglion cell axotomy, three populations of cells can be recognized in the ganglion cell layer of the chick retina. These are: 1) Irregularly shaped cells, which are not affected by axotomy and lack Nissl stain. They comprise about 5% of the total cell population and are probably glial cells. 2) Small cells which have a distinctive teardrop-shaped perikarya, stain for Nissl substance, and are not affected by axotomy. They occur with a uniform density of about 4,000 cells/mm2 across the entire retina and comprise 30-35% of the total number of cells in the ganglion cell layer. It is suggested that these cells are displaced amacrine cells. 3) Cells which stain strongly for Nissl substance and disappear after axotomy. These cells comprise 60-65% of the population of cells in this layer. The density of the latter cells varies throughout the retina. A high-density region in the central area extends into the superior-temporal retina. This high-density region corresponds to a position in the lateral visual field extending into the infero-frontal field. The total number of these cells agrees with the reported number of the optic nerve fibres in the chick, (Rager and Rager, '78); therefore they are presumably ganglion cells. The size distribution of the presumptive ganglion cells varies in different parts of the retina. The only previous study of the distribution and size of cells in the ganglion cell layer of the avian retina did not distinguish between ganglion cells and displaced amacrine cells (Binggeli and Paule, '69). The present results are therefore likely to be a more accurate description of the total number of ganglion cells, the regional variations in their density, and the characteristics of their size than previously reported.

Animals↗
PubMed1991

Reinnervation of developing rat muscle by non-axotomized motoneurons.

To study the ability of developing motoneurons to reinnervate their denervated muscle, axotomized motoneurons in rat neonates and pups were retrogradely labeled with two fluorescent tracers. Fluorogold (FG), a long-lasting fluorescent dye, was injected into intercostal muscle T8 to retrogradely label the motoneurons that innervated it. Two days later intercostal nerves T7-T9 were cut. The intercostal muscle denervated at birth was reinnervated within 10-20 days, as evidenced by nerve-evoked muscle contraction. Three weeks following axotomy, tetramethylrhodamine isothiocyanate (TRITC) was injected into the same muscle to label the motoneurons that reinnervated it. The motoneurons double-labeled with FG and TRITC were, therefore, axotomized motoneurons that regenerated to reinnervate T8. In neonates, axotomy resulted in a significant reduction in the number of FG-labeled motoneurons, which suggests that axon transection at early postnatal days causes a massive motoneuron death. The percentage of double-labeled motoneurons was significantly smaller than that in non-axotomized rats. TRITC-labeled motoneurons constituted the majority of stained motoneurons; these were located in different nuclei than the intercostal motoneurons. These findings suggest that muscle reinnervation is, at least in part, by motoneurons which originally did not innervate intercostal muscle T8. Unlike axotomy at birth, axotomy performed 2-3 weeks after birth did not result in a significant motoneuron loss. The number of stained motoneurons labeled with both FG and TRITC was significantly smaller, however, than in non-axotomized spinal cords. Our data indicate that in pups only a small percentage of axotomized motoneurons reinnervated the denervated muscle.

Animals↗
PubMed1994

Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons.

Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy-induced reduction in transmitter markers [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE) in neonatal or adult animals or the axotomy-induced up-regulation of the low-affinity neurotrophin receptor p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75NGFR in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype.

Acetylcholinesterase↗
PubMed1990

Differential regulation of peripherin and neurofilament gene expression in regenerating rat DRG neurons.

Quantitative in situ hybridization and RNA blotting methods were used to define the time course and magnitude of changes in expression of mRNAs encoding peripherin and the neurofilament (NF) triplet proteins in rat dorsal root ganglion (DRG) neurons during axonal regeneration. mRNA levels in adult rat L4 and L5 DRGs were examined in autoradiograms after in situ hybridization with specific 35S-labeled cDNA probes 1-56 days following unilateral crush lesions of the sciatic nerve. The results of quantitative analyses indicated that peripherin mRNA levels were significantly increased in large-sized (greater than 1000 microns 2) DRG neurons at 7, 14, and 28 days after axotomy while the mRNA levels for each of the NF triplet proteins were significantly decreased at these same time points. The mRNA levels of the low (NF-L) and middle (NF-M) sized NF subunits were significantly decreased as early as 1 day postaxotomy but the mRNA level of the large NF subunit (NF-H) did not change until 7 days after axotomy. The maximal reduction in NF mRNA levels was observed at 14 days postaxotomy when NF-L mRNA levels were only 35% of those in large-sized, normal control neurons. Recovery toward normal levels of both NF and peripherin mRNAs was observed at 8 weeks postaxotomy. RNA blot analyses with total RNA obtained from DRGs at different postaxotomy times confirmed that NF-L mRNA levels were reduced in the DRG during the first 4 weeks after axotomy but, interestingly, failed to detect an increase in peripherin mRNA levels. This difference concerning peripherin mRNA levels in axotomized preparations obtained by RNA blotting vs. in situ hybridization was attributed to the fact that RNA blots utilized total DRG RNA which includes mRNAs from both small and large-sized DRG neurons. A recent in situ hybridization study showed that the small-sized DRG neurons which contain the majority of the peripherin mRNA in the DRG do not increase their peripherin mRNA levels 14 days after axotomy (Oblinger et al., 1989b). This may mask any change in the large neuron response when total RNA is examined. Overall, the results of this study demonstrate (1) that type III (peripherin) and type IV (NF) intermediate filament genes are regulated differently during axonal regeneration, and (2) that the three NF genes are down-regulated in a fairly coordinate manner during regeneration. These data suggest that an important component of the regeneration program is the alteration of the composition of the IF component of the cytoskeleton.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Corticospinal neurons exhibit a novel pattern of cytoskeletal gene expression after injury.

We examined changes in the expression of major cytoskeletal protein mRNAs in adult hamster corticospinal neurons after axotomy. While a number of studies had determined that peripheral neurons exhibit major alterations in cytoskeletal gene expression after axotomy, no previous studies had addressed the question of whether or not intrinsic mammalian CNS neurons, which do not have the ability to successfully regenerate axons after injury, alter their expression of tubulin and neurofilament genes after injury. In the present study we used in situ hybridization methods to examine this issue. 35S-labeled cDNA probes for the low molecular weight neurofilament protein (NF-L) mRNA and an alpha-tubulin mRNA species (M alpha 1) were used for in situ hybridizations of sections of the sensorimotor cortex obtained 2, 7, and 14 days after unilateral axotomy of the corticospinal tract in the caudal medulla. Film as well as emulsion autoradiography showed dramatic decreases in both alpha-tubulin and NF-L mRNA levels within axotomized neurons in layer Vb of the sensorimotor cortex. Tubulin mRNA levels were decreased as early as 2 days after injury whereas NF-L mRNA levels were not decreased until later times. Ribosomal RNA (rRNA) levels in axotomized corticospinal neurons were also examined using in situ hybridization with a 35S-labeled rDNA probe. These studies showed only a slight decrease in rRNA levels in corticospinal neurons at 14 days after axotomy. Immunoblotting experiments of total protein from corticospinal axons in the medulla were performed to assess whether the axonal composition immediately proximal to the injury site reflected changes in cell body gene expression. Both alpha-tubulin and NF-L levels were found to decrease in corticospinal axons by 28 days after injury. These findings, to our knowledge, are the first to demonstrate that a class of mammalian CNS neurons have an intrinsically different cytoskeletal response to axonal injury than do PNS neurons. The failure to upregulate tubulin gene expression following injury may contribute to the ineffective regenerative response of these long-tract CNS neurons.

Amidines↗
PubMed1993

Evidence for activation of astrocytes via reactive microglial cells following hypoglossal nerve transection.

Following peripheral nerve injury, resident microglial cells proliferate and astrocytes undergo hypertrophy, as evidenced, e.g., by an increase in the levels of glial fibrillary acidic protein (GFAP). In a previous study we have shown that infusion of cytosine arabinoside (ARA-C) into the rat brain blocks the axotomy-induced proliferation of microglial cells. This experimental approach has been used in the present study in order to explore the issue of whether the reactive microglial cells are mediators of the increased GFAP expression in the hypoglossal nucleus of the rat following axotomy. Quantitative analysis of sections processed for immunocytochemistry or in situ hybridization demonstrated a marked increase in GFAP-like immunoreactivity and GFAP-mRNA, respectively, in the ipsilateral hypoglossal nucleus 4 and 7 days after axotomy in control experiments. These increases failed to occur in axotomized animals treated with ARA-C. Therefore, our data are compatible with the hypothesis that activation of astrocytes following axotomy as measured by increased expression of GFAP and its mRNA is induced secondarily to the microglial response.

Animals↗
PubMed1993

Influences of neurotrophins on mammalian motoneurons in vivo.

Several recently reported investigations have shown that a member of the neurotrophin family of neuronal growth factors, brain-derived neurotrophic factor (BDNF), supports motoneurons in vitro and rescues motoneurons from naturally occurring and axotomy-induced cell death (Oppenheim et al., 1992b; Sendtner et al., 1992b; Yan et al., 1992; Koliatsos et al., 1993; Henderson et al., 1993). In the current study, we have explored the issue of whether BDNF and other neurotrophins act to regulate motoneuron survival during development and asked whether synthesis of motoneuron transmitter enzymes is also regulated. We first examined whether spinal motoneurons in newborn animals could retrogradely transport iodinated neurotrophins from their targets in a specific, receptor-mediated manner. We found that motoneurons readily transported NGF, BDNF, and neurotrophin-3 (NT-3). The retrograde transport of one factor could be completely or largely blocked by excess of unlabeled homologous factor, but only partially blocked by excess of unlabeled heterologous factors. Since previous studies have shown that these three neurotrophins bind to the low-affinity NGF receptor, p75NGFR, with similar affinity, our data suggest that the retrograde transport of neurotrophins by motoneurons may be mediated by additional components, such as the trk family of proto-oncogenes. Consistent with this hypothesis, we demonstrate here that motoneurons express mRNA for two members of the trk family, trkB and trkC. Furthermore, both trkB and trkC were expressed by E13, consistent with a role for BDNF and NT-3 in regulating important developmental events involving motoneurons such as naturally occurring cell death. In order to determine which members of the neurotrophin family influence motoneuron survival and to assess the generality of their effects, we evaluated the abilities of NGF, BDNF, and NT-3 to save both spinal and cranial motoneurons after neonatal axotomy. Locally applied BDNF saved 40-70% of motoneurons which would ordinarily die after axotomy in lumbar and cranial motor pools, depending on the treatment protocol employed. NT-3 also exhibited some ability to rescue motoneurons and saved 20-25% of motoneurons which would die in the absence of treatment. Finally, we asked whether neurotrophins could influence synthesis of transmitter enzymes by motoneurons as well as their survival after axotomy. Locally applied BDNF and NT-3 could partially prevent the decrease of protein contents in L4 and L5 ventral roots which normally follows sciatic nerve transection. However, treatment with these neurotrophins did not prevent the decrease in choline acetyltransferase (ChAT) activity in L4 and L5 ventral roots which results from this procedure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Traumatically induced axonal damage: evidence for enduring changes in axolemmal permeability with associated cytoskeletal change.

Recent studies have demonstrated that delayed or secondary axotomy is a consistent feature of traumatic brain injury in both animals and man. Moreover, these studies have shown that the pathogenesis of this secondary axotomy involves various forms of initiating pathology, with the suggestion that, in some cases, only the axonal cytoskeleton is perturbed, while, in other cases, both the axonal cytoskeleton and related axolemma manifest traumatically induced perturbations. In the current communication, we continue in our investigation of the significance of these traumatically induced alterations in axolemmal permeability and their relation to any related intra-axonal cytoskeletal change. This was accomplished in cats which received intrathecal infusions of peroxidase, an agent normally excluded by the intact axolemma. These animals were subjected to traumatic brain injury, and sites showing altered axolemmal permeability to the peroxidase were assessed at the light and electron microscopic level. Through this approach, we recognized that a traumatic episode of moderate severity evoked changes in axolemmal permeability which surprising endured for up to 5 hrs postinjury. At such focal sites of altered permeability, the related cytoskeleton showed a statistically significantly neurofilament compaction, with the strong suggestion of concomitant neurofilament sidearm loss, microtubular dispersion, and mitochondrial abnormality. Over time, these events led to further disorganization of the axonal cytoskeleton which translated into impaired axoplasmic transport and secondary axotomy. Most likely, these alterations in axolemmal permeability result in either the direct or indirect effects upon the axonal cytoskeleton that precipitate the damaging sequences resulting in delayed axotomy.

Animals↗
PubMed1986

The axon reaction in spinal ganglion neurons of acrylamide-treated rats.

Rats were given acrylamide in doses of either 30 or 50 mg/kg (5 days each week) for up to 3 weeks and killed at weekly intervals. The right sciatic nerve was tied tightly at the level of the major trochanter 4 days before killing the animals by perfusion fixation when ipsilateral and contralateral sensory ganglia (L5 and L6) were removed. The effects on neuronal perikarya of axotomy alone, of acrylamide alone and of these combined were studied by light and electron microscopy. The responses to axotomy and to acrylamide intoxication shared certain features, namely peripheral Nissl substance and to a lesser degree nuclear eccentricity, nucleolemmal crenation and mitochondrial enlargement. Neurofilament loss was present only with acrylamide. In combined axotomy and acrylamide all these five features were prominent. These findings indicate firstly that the individual responses to axotomy and to acrylamide, while sharing several features, are subtly different and secondly that acrylamide appears to impede the vital neuronal responses directed towards repair of the axon.

Acrylamide↗
PubMed1994

The ganglion cell response to optic nerve injury in the cat: differential responses revealed by neurofibrillar staining.

The early responses of cat retinal ganglion cells to axotomy have been examined using neurofibrillar and Nissl-stained wholemounts. We were interested to learn whether the enhanced neurofilament expression, seen in a number of neuronal systems, was also present in different neuronal populations of the cat retina and could be used to study the distribution of these cells. We found that beta ganglion cells degenerate very rapidly after axotomy with the nuclei becoming pyknotic within a few days. Few beta cells showed increased neurofibrillar staining of the dendrites. The cell body degenerated prior to any visible degenerative changes in the axon. A proportion of the alpha and gamma ganglion cells degenerated in the first two to three weeks after axotomy. The alpha cells underwent markedly enhanced neurofibrillar staining of their dendrites prior to degeneration. The Nissl material of the cell bodies diminished as the cells degenerated but we have not observed pyknotic nuclei. The dendritic trees of some axotomised gamma cells were also revealed by the neurofibrillar stain three weeks after axotomy. These results show that retinal ganglion cells do not degenerate by a dying back process. We suggest that the rapid degeneration of the beta ganglion cell population comes about by excitotoxic cell death, a consequence of their large glutamatergic input from bipolar cells. The degenerating beta ganglion cells have the morphological appearance of cells undergoing apoptosis.

Animals↗
PubMed1990

Effect of optic nerve transection upon myelin protein gene expression by oligodendrocytes: evidence for axonal influences on gene expression.

The effect of optic nerve transection on myelin protein gene expression was studied in rats following axotomy at two ages: during active myelination (17 days of age) and after peak expression of the genes (35 days of age). mRNA levels for proteolipid protein, myelin basic protein and myelin-associated glycoprotein were assessed by northern and dot blotting and by in situ hybridization using tissue sections and cultured individual oligodendrocytes. Transection at 17 days caused down-regulation of mRNAs for proteolipid protein, myelin basic protein and myelin-associated glycoprotein by 5 days after axotomy with an increase in GFAP mRNA. A more protracted change followed axotomy at 35 days of age. The abundance of mRNAs for proteolipid protein and myelin basic protein was significantly reduced by 28 days after transection in the affected nerve. Quantification of proteolipid protein mRNA expression in individual oligodendrocytes confirmed the down-regulation. However, in contrast to the effects on the major myelin proteins, the abundance of myelin-associated glycoprotein mRNA increased in the affected nerve for at least the initial month after lesioning at 35 days. The results show that optic nerve transection has significant effects on myelin protein mRNA expression in oligodendrocytes of optic nerve. However, the changes in myelin protein gene activity are relatively small and more protracted than those seen in Schwann cells after peripheral nerve section. Because axotomy also causes marked changes in the glial population of the optic nerve it is not possible unequivocally to ascribe the alteration in gene expression to loss of axons. However, the data may provide evidence that axons do influence myelin protein genes in oligodendrocytes and are necessary for them to develop their full expression.

Animals↗
PubMed1994

Comparison of changes in beta-tubulin and NF gene expression in rat DRG neurons under regeneration-permissive and regeneration-prohibitive conditions.

To examine the question of whether or not prevention of axonal regrowth after injury affects the molecular responses of neurons to axotomy, Northern blotting and in situ hybridization were used to study changes in the mRNA levels of neurofilament (NF) proteins and tubulins in rat dorsal root ganglion (DRG) cells. Adult male rats sustained either a crush lesion of the mid-sciatic nerve (regeneration-permissive condition) or a cut lesion of the sciatic nerve combined with ligation of the proximal nerve stump and removal of a large segment of the distal nerve (regeneration-prohibitive condition). At 14 days post-injury, the relative levels of the low (NF-L) and middle (NF-M) molecular weight NF protein mRNAs, as well as those of beta II- and beta III-tubulin, were examined in the L4 and L5 DRG. The data showed that the levels of NF-L and NF-M mRNAs decreased while beta II- and beta III-tubulin mRNA levels increased in the DRG after either crush axotomy or cut/ligation axotomy of the sciatic nerve, suggesting that the elicitation of these molecular changes by axon disconnection is independent of the ultimate success or failure of the axonal regrowth process. However, cut/ligation axotomy had a more pronounced effect than did crush injury on the mRNA changes. This result suggests that feedback mechanisms from regrowing axons are important in regulating the extent of the cytoskeletal mRNA changes in injured neurons.

Animals↗
PubMed1985

Ornithine decarboxylase in motoneurons during regeneration.

The activity of ornithine decarboxylase, the rate-limiting enzyme in polyamine synthesis, was assayed in the isolated facial nucleus of the rat at various times after axotomy of the facial nerve. In addition, it was measured 24 h after the second of a series of two lesions (conditioning lesion design) with various times between the first and second operations. Ornithine decarboxylase activity was found to increase 8 h after nerve transection and was maximum after 24 h (300% of control). Thereafter the activity declined to subnormal levels where it remained for several weeks. Ornithine decarboxylase activity did not increase again when a second axotomy was made 2 weeks after the first lesion. However, ornithine decarboxylase did respond to the second axotomy if it was carried out 3 weeks after the first lesion. Histochemical localization of ornithine decarboxylase demonstrated that the increase in enzyme activity was mainly confined to the perikarya of the motoneurons. These data suggest that this enzyme is somehow involved in triggering the "regeneration program" and clearly indicate that at least some aspects of the neuronal response to axotomy are not further stimulated by a conditioning lesion.

Animals↗
PubMed1992

Testosterone fails to save androgen-sensitive rat motoneurons following early target removal.

Axotomy during development can result in the death of up to 100% of the affected motoneurons. However, axotomy-induced death can be significantly reduced by administration of androgens in young rats. Motoneuron death in the spinal nucleus of the bulbocavernosus (SNB) has previously been shown to be regulated by androgens during development. the present experiment examined the effects of androgen treatment on the survival of SNB motoneurons after target removal and concomitant axotomy early in development. On the day of birth, two target muscles of SNB motoneurons of male and female rats were bilaterally extirpated. Target removal resulted in a dramatic loss of SNB motoneurons within 48 h of surgery, with an ultimate loss of virtually all motoneurons projecting to the extirpated muscles by postnatal day 10. Treatment with testosterone failed to save SNB motoneurons from target removal-induced death. Pups treated with testosterone after target removal did not differ in the pattern or timing of motoneuron loss from untreated pups at any age examined. Counts of degenerating cells in the SNB reflected the extensive motoneuron loss and also did not differ with testosterone treatment. These results indicate that testosterone cannot save the androgen-sensitive SNB motoneurons from death after target removal and concomitant axotomy early in development. The failure of testosterone treatment to rescue SNB motoneurons in the absence of the SNB target musculature further suggests that during normal development, both androgens and target muscles are necessary for SNB motoneuron survival.

Androgens↗
PubMed1990

Target dependence of motoneuronal survival: the current status.

The concept that target-derived molecules are essential for the maintenance of motoneuronal survival has now received considerable support from different sources. One source of information arises from the target-related motoneuron death that occurs naturally at early developmental stages. Another source of information arises from axotomy-induced motoneuron death in adulthood. During development, the survival of motoneurons is initially target-independent. Its target dependence is expressed at a certain embryonic stage and, subsequently, motoneuronal survival becomes less dependent upon the target. It is not known how the state-switch of motoneurons is induced during development. Also, it is not certain whether naturally occurring motoneuron death during development and axotomy-induced motoneuron death in adulthood are based on the same mechanisms. Axotomy induces injury-associated disturbance in the motoneurons, in addition to elimination of the target-derived trophic supply. At present, there is no direct evidence that axotomy-induced motoneuron death in adulthood results solely from the deprivation of trophic factors from the target. The survival of motoneurons in adulthood appears to be maintained by multiple mechanisms. Some of the tropic factors that are involved in the maintenance of neuronal phenotypic expression are distinct from those involved in the maintenance of neuronal survival. There are multiple target-derived trophic factors for a given neuron.

Animals↗
PubMed1989

Amphibian sympathetic ganglia as a model system for investigating regeneration in the vertebrate peripheral nervous system.

1. The paravertebral sympathetic ganglion of the bullfrog serves as an excellent experimental system in which to study the response of vertebrate neurones to axotomy and the mechanisms associated with regeneration. 2. Various types of lesions to the axons (axotomy) of these neurones promote distinct and reproducible changes in the electrophysiological properties of the cell bodies which are not a consequence of changes in cell body morphology. 3. The axotomy-induced increase in spike width and decrease in the amplitude of the action potential after-hyperpolarization may allow an increase in Ca2+ influx and thereby promote regrowth. 4. The axotomy-induced decrease in after-hyperpolarization duration may reflect the disconnection of the neurone with its target and the loss of available nerve growth factor (NGF) from the target. 5. Experiments with NGF antibodies provide evidence that an NGF-like substances serves to maintain the normal electrophysiological characteristics of amphibian sympathetic neurones.

Amphibians↗
PubMed1995

Effects of an acute muscle nerve section on the excitability of dorsal horn neurones in the rat.

A previous study of this laboratory showed that an acute myositis (which is associated with increased activity in slowly conducting muscle afferent fibres) is followed by marked excitability changes in the dorsal horn within a few hours. The present work addresses the question as to how the responsiveness of dorsal horn neurones changes when the same muscle nerve is transected. In anaesthetized rats, an axotomy of the gastrocnemius-soleus (GS) muscle nerves was performed and the electrical and mechanical excitability of single dorsal horn neurones in the lumbar spinal cord determined 2-8 h after the lesion. Axotomy led to a decrease in the proportion of neurones responding to A-fibre input from the cut nerve and to an increase in the efficacy of sural and peroneal nerve stimulation. The change in GS input became significant only 5-8 h after the lesion and could reflect the beginning of neuroplastic changes. The change in sural and peroneal input was most marked 2-5 h after axotomy and is probably due to fast neuronal processes. The efficacy of C-fibre input from the sural and peroneal nerves increased significantly in the lateral dorsal horn only. In comparison with the effects of an acute myositis, the axotomy had opposite effects with regard to the GS input, but similar effects with regard to the C-fibre drive from the other nerves. It is concluded that transection of a muscle nerve is similarly effective in inducing acute changes in dorsal horn excitability as is an increase in muscle nerve activity.

Animals↗