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Shortlasting increase in the synthesis and utilization of noradrenaline due to Axotomy-induced irritation.

The synthesis and the utilization of noradrenaline in the caudal and cranial part of intact and sectioned rat spinal cords were determined at 20 h or for 30 min--2 h after an operation. The synthesis and the utilization of noradrenaline in the caudal part of spinal cords transected 20 h previously were retarded as compared to those in the cranial part of sectioned cords or in the caudal part of intact cords. The synthesis of noradrenaline was stimulated in the caudal part of the spinal cord when measured for 30 min after a transection. The utilization of noradrenaline in the spinal cord caudal to a transection was not decelerated during 2 h after an operation. Local application of lidocaine to the cord prior to the cut changed the synthesis and the utilization of noradrenaline in both parts of the spinal cord to values similar to those obtained 20 h after the operation. Transection of the spinal cord might stimulate the synthesis and the utilization of noradrenaline by a shortlasting mechanical irritation of neurons cut by the lesion.

Animals↗

Neuronal and nonneuronal influences on retinal ganglion cell survival, axonal regrowth, and connectivity after axotomy.

In contrast to the abortive regrowth that occurs when axons are interrupted in the adult mammalian CNS, exposure of injured CNS axons to the nonneuronal milieu of a peripheral nerve can lead to extensive axonal elongation. With the application of this experimental approach to the retinocollicular pathway in adult rodents, it has been possible to investigate the influences of neuron-glia and other interactions on the capacity of axotomized CNS neurons to survive injury, to elongate the distances necessary to reach specific targets, and to form connections in the CNS in adult rodents. The results of these investigations indicate that the changed glial environment provided by peripheral nerve grafts permits the guided regeneration of RGC axons to their CNS targets. Back in the CNS glial environment, regenerated axons penetrate their targets for short distances and re-form normal appearing synapses that can excite or inhibit postsynaptic neurons. Further studies will require a better understanding of intrinsic neuronal properties and of the interactions of these neurons with other neurons and with the cellular and noncellular components of the extraneural milieu.

Animals↗

Axotomy mimicked by localized colchicine application.

Comparable depression of synaptic transmission in the avian ciliary ganglion resulted from either section or localized colchicine treatment of the ciliary nerves. Both colchicine treatment and axotomny produced similar changes in RNA distribution in the cell bodies as well. Colchicine did not directly affect transmission, and action potential propagation along the ciliary nerves was normal. Interference with axoplasmic transport of material in both cases is postulated to signal the observed chromatolytic changes.

Action Potentials↗

Insulin and metabolic efficiency in rats. I. Effects of sucrose feeding and BAT axotomy.

The role of insulin and brown adipose tissue (BAT) thermogenesis in metabolic efficiency (ME, the efficiency of body wt gain) was examined in rats with varied basal insulin status. Long-lasting insulin was administered using a protocol that did not alter food intake, yet increased ME in both groups. Half the rats were fed sucrose to stimulate BAT growth and thermogenesis. Insulin overrode the exaggerated decrease in ME in sucrose-fed diabetics, with only partial attenuation in controls. Interscapular BAT (IBAT) lipoprotein lipase activity was decreased in diabetic rats, restored by insulin treatment, and not affected in controls. Sucrose-fed diabetics and controls had their IBAT sham or bilaterally surgically denervated. Insulin decreased the thermogenic potential of BAT [cytochrome oxidase activity (COA)] in intact controls and diabetics; in the latter, insulin restored COA independent of BAT innervation. We conclude that insulin can increase ME without an associated increase in energy intake, regardless of basal insulin status, both insulin deficiency and excess decrease BAT thermogenic potential (COA), and hyperinsulinemia-induced increases in ME may result from decreased BAT mitochondrial proliferation.

Adipose Tissue, Brown↗

Reinnervation by axon collaterals from single facial motoneurons to multiple muscle targets following axotomy in the adult guinea pig.

To study the process of recovery from facial palsy experimentally, the location of cranial motoneurons supplying the posterior belly of the digastric muscle (PDG) and the extratemporal portion of the facial nerve trunk was examined in a double-labeling paradigm using two retrograde tracers in the adult guinea pig of which the facial nerve had been surgically injured. In different stages after the induced facial palsy had recovered functionally (4-13 weeks after the surgical operation), wheat germ-agglutinated horseradish peroxidase (WGA-HRP) was injected into the PDG and Fluoro-Ruby (FR) was applied to the proximal cut end of the extratemporal portion of the facial nerve trunk. Distribution of neurons retrogradely labeled with WGA-HRP and/or FR was plotted in the brainstem and compared with that of the controls. In the intact cases, HRP-labeled neurons were restrictedly seen in the accessory facial nucleus (Acs7), while FR-labeled neurons were found within the main facial nucleus (FMN). In the axotomized cases: (1) HRP-labeled neurons were seen diffusely in the Acs7 as well as in the FMN, where normal myotopical representation no longer seemed to be maintained. (2) FR-labeled neurons were also observed diffusely in the FMN and the Acs7. (3) A considerable number of neurons were doubly labeled with WGA-HRP and FR in both the Acs and the FMN in cases with shorter survival periods (4-7 weeks), but not in cases with longer survival periods (12-13 weeks). Thus, new findings show that connections are temporarily maintained by single, facial motoneurons with axon collaterals to multiple muscle targets in adult mammals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Morphological changes and functional recovery following axotomy of a serotonergic cerebrobuccal neurone in the land snail Achatina fulica.

We have examined an identified serotonergic neurone in Achatina fulica and described the normal morphological and physiological characteristics of this cell. Injury-induced changes in this neurone following in vivo recovery are described and compared with in vitro gastropod models of regeneration. Nickel-lysine and biocytin dye-fills of the metacerebral giant (MCG) neurone, together with serotonin-like immunoreactivity, revealed an extensive innervation of the ipsilateral buccal ganglion, much greater than that previously reported. Labelled MCG fibres were seen to ramify throughout the ganglion, providing extensive neuropilar innervation. Serotonin-immunoreactive fibres were seen not only within the neuropile but also within the cell body layer of the buccal ganglia, surrounding many of the cell bodies with varicose fibres. Dye-fills also revealed a minor contralateral buccal innervation not previously described. This view of a predominantly ipsilateral innervation of the buccal ganglia by the MCG was supported by electrophysiological measurements. The ipsilateral buccal follower cell B1 displayed an increase in depolarization in response to repeated trains of action potentials to the MCG, whereas the contralateral B1 showed only a weak depolarization in response to the identical stimuli. Following a crush to the cerebral-buccal connective (CBC), the MCG rapidly regenerated its injured projections, displaying both morphological and physiological recovery within 5-10 days. The original, severed fibres of the MCG were, however, replaced by a multitude of smaller neurites, which persisted for up to 3 months (the longest recovery period examined). Despite this morphological difference between normal and regenerated fibres, the MCG re-established functionally equivalent connections upon B1. In contrast with previous in vitro studies using gastropods, serotonin-like immunoreactivity revealed that severed distal fibres from the MCG rapidly degenerated (2-6 days), resulting in a transient unilateral depletion of serotonin in the buccal ganglia. We suggest that this loss of serotonin in the lesioned ganglion may play a functional role in regeneration, as has been suggested in vitro.

Animals↗

[Changes of trkB and trkC mRNA in facial nucleus after axotomy and end-to-end anastomosis in the rat].

OBJECTIVE: To explore the changes of receptor tyrosine kinase B and C (trkB and trkC) mRNA in facial motoneurons following facial nerve injury and repair. METHODS: The time course of trkB and trkC mRNA in facial motoneurons following facial nerve transection and anastomosis was analyzed using in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction(RT-PCR) in adult rats. RESULTS: In the facial nerve simple transection group, the intensity of trkB mRNA signal began to increase to 3d post-operation and to its maximum at 7d. Then, the intensity started to decrease at 14d, but it was still higher than that in the contralateral side at 35 d. After facial nerve injury, the changing trend of trkC mRNA was in the contrary to that of trkB. In the group of anastomosis, the changing trend of the intensity of trkB and trkC mRNA signal in the lesioned side was almost the same as that in the transection group. However, the intensity of trkB and trkC mRNA signal in the lesioned side returned to normal level at 35d. The finding obtained by RT-PCR was consistent with that of ISH. The statistic t-test showed significant differences between the two groups for the relative density level of positive band for trkB and trkC at 21d, 35d post-operation, respectively, (ttrkB,21 = 13.795, ttrkC,21 = 7.445, ttrkB,35 = 8.560, ttrkC,35 = 10.132, P < 0.01). CONCLUSIONS: Transection of the facial nerve results in a upregulation of trkB mRNA, but a downregulation of trkC mRNA in axotomized facial motoneurons. The immediate anastomosis can't counteract and attenuate the changes of trkB and trkC induced by the nerve injury, but whether the changes of trkB and trkC return to normal level depends on the regeneration facial nerve.

Anastomosis, Surgical↗

Hemopexin is synthesized in peripheral nerves but not in central nervous system and accumulates after axotomy.

In adult mammals, injured axons regrow over long distances in peripheral nerves but fail to do so in the central nervous system. Analysis of molecular components of tissue environments that allow axonal regrowth revealed a dramatic increase in the level of hemopexin, a heme-transporting protein, in long-term axotomized peripheral nerve. In contrast, hemopexin did not accumulate in lesioned optic nerve. Sciatic nerve and skeletal muscle, but not brain, were shown to be sites of synthesis of hemopexin. Thus, hemopexin expression, which can no longer be considered to be liver-specific, correlates with tissular permissivity for axonal regeneration.

Amino Acid Sequence↗

Effect of axotomy on cholinergic enzyme activities in the spinal cord and sciatic nerve of the dog.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity measured in the ventral and dorsal part of the dog spinal cord (L6-S2) and in the stumps of the sciatic nerve 5, 10, 15 and 21 days after its transection were compared with the corresponding activities in the intact contralateral nerve and in sham-operated animals. AChE was also examined histochemically. Changes in the enzyme activities in the central nerve stump were correlated with activity changes in the spinal cord. In the central nerve stump, a marked (25%) increase in AChE activity was found on the fifth day after transection, but by the 21st day it fell below control value levels; up to the 15th day it showed good correlation with AChE activity in the ventral spinal cord. Histochemically, pronounced reduction of enzymatic activity was found in the ipsilateral part of the spinal cord. On the 15th day, ChAT activity in the ventral spinal cord was also significantly decreased and the accumulation of the enzyme in the central nerve stump was negligible. On the contrary, at the last 21-day interval examined, a significant increase in ChAT activity and a nonsignificant increase in AChE activity was found in the spinal cord, but their activities in the central nerve stump were decreased. In the degenerated peripheral nerve stump ChAT activity dropped by an average of 99% and AChE activity by 48% during the first 15 days after transection but, on the 21st day, AChE activity was 22% higher than at the preceding interval.

Acetylcholinesterase↗

Effects of the external ions and metabolic poisoning on the constriction of the squid giant axon after axotomy.

After transecting the squid giant axon in the presence of an artificial external medium, which was composed of the ions normally present in squid blood, the cut ends of the axon constrict. This constriction could be completely blocked by cutting the axon in the presence of an artificial internal medium composed of the ions normally present inside the axon. By interchanging the ions in the internal medium with those in the external medium, it was determined that constriction was stimulated by the high concentrations of calcium, chloride, and magnesium ions present in the external medium and inhibited by the high concentrations of potassium ion in the internal medium. Constriction could also be inhibited by 2,4-dinitrophenol and cyanide. Softening of axoplasm and elution of the axoplasmic proteins at the cut end of the axon also occurred in the external medium. This softening and elution may be necessary for constriction since constriction occurred only in those media that also induced axoplasmic softening and elution. Softening and elution are not sufficient for constriction, however, since high potassium, 2,4-dinitrophenol, and cyanide inhibited constriction without inhibiting the softening or elution of axoplasm.

2,4-Dinitrophenol↗