The time course of noradrenaline decrease in rat spinal cord following transection
Abstract
The time course of degeneration of bulbospinal monoamine neurones following spinal cord transection was studied biochemically and histochemically in 3 consecutive 1 cm parts distal to transection. In the part immediately below transection clear degenerative changes were found on day 2, in the more distal part on day 4, and latest in the most distal part. This time-sequence of nerve terminal degeneration is probably related to the interruption of the comparatively slow intra-axonal transport in these neurons. The results indicate a complex situation in the nerve terminal-receptor area in the caudal part of the spinal cord following transection.
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Cited by (25)
Catecholamine enzymes and neuropeptides are expressed in fibres and somata in the intermediate gray matter in chronic spinal rats
1997, NeuroscienceSpinal cord injury disrupts control of sympathetic preganglionic neurons because bulbospinal input has been lost and the remaining regulation is accomplished by spinal circuits consisting of dorsal root afferent and spinal neurons. Moreover, an initial retraction and regrowth of dendrites of preganglionic neurons in response to deafferentation creates the potential for remodelling of spinal circuits that control them. Although catecholamines and neuropeptide Y are found in descending inputs to the preganglionic neurons, their presence in spinal circuits has not been established. Spinal circuits controlling preganglionic neurons contain substance P but participation of these peptidergic neurons in remodelling responses has not been examined. Therefore, we compared immunoreactivity for the catecholamine-synthesizing enzyme dopamine β-hydroxylase, for neuropeptide Y and for substance P in the intermediate gray matter of the spinal cord in control rats and in rats seven or fourteen days after transection at the fourth thoracic cord segment. Sympathetic preganglionic neurons were retrogradely labelled by intraperitoneal injection of the tracer FluoroGold. These experiments yielded three original findings. 1) At one and two weeks after cord transection, fibres and terminals immunoreactive for dopamine β-hydroxylase and neuropeptide Y were consistently found in the intermediolateral cell column in segments caudal to the transection. The area of fibres and terminals containing these immunoreactivities was markedly reduced compared to control rats or to segments rostral to the transection in the spinal rats. 2) Immunoreactivity for substance P was increased after cord transection and the distribution of fibres immunoreactive for this peptide in segments caudal to the transection extended more widely through the intermediate gray matter. These reactions demonstrated a plastic reaction to cord transection by spinal neurons expressing substance P. 3) Dopamine β-hydroxylase expression was up-regulated in somata within the intermediate gray matter of spinal segments caudal to the transection. The numbers of somata immunoreactive for this enzyme increased six-fold by fourteen days after cord transection, compared to the few somata counted in control rats.
In conclusion, the presence of a catecholamine synthesizing enzyme and neuropeptides in fibres surrounding sympathetic preganglionic neurons caudal to a cord transection suggests a source of catecholamines and these peptides within spinal circuits in the chronic spinal rat. The presence of dopamine β-hydroxylase in a markedly greater number of neuronal somata after cord transection reflects significant up-regulation of gene expression and may indicate a switch by these neurons to an adrenergic phenotype, revealing a plastic response to injury within the spinal cord.
The effects of clonidine and yohimbine on locomotion and cutaneous reflexes in the adult chronic spinal cat
1987, Brain ResearchThe effects on the locomotor pattern of a noradrenergic agonist (clonidine) and an antagonist (yohimbine) were studied in 3 adult chronic spinal cats walking on a treadmill. In the early post-transection period, when the cat walked mainly on the tip of its feet, without supporting its own weight, it was observed that clonidine (150 μg/kg) could induce a good bilateral foot placement and intermittent complete weight support. When clonidine was given 1–3 months following the transection, at a time when the spinal cats had a stable and regular locomotor performance, the step lenght increased markedly, especially at low speeds. This was associated with an increase in the duration of the flexor and extensor bursts, as well as an increase of the angular excursion of all joints. These effects, seen during forward locomotion, were also observed during backward locomition. In addition, the latter was more easily elicited after clonidine. Yohimbine (1.5–3 mg/kg) partially antagonized these effects. The threshold current needed to elicit a small flexion reflex through wires implanted in the dorsum of the paw was 2–3 times higher after clonidine. Trains of shocks in the animal, standing quietly, did not induce the prolonged late discharges normally found in acute spinal cats. Fast paw shaking, elicited by dipping one paw in water, was abolished by clonidine and reappeared after yohimbine. These results indicate that noradrenergic drugs may influence both spinal locomotion and the excitability of cutaneous reflexes. This class of substances could thus play a useful role in the recovery and/or maintenance of locomotor functions after spinal trauma.
A comparison of the distribution of central cholinergic neurons as demonstrated by acetylcholinesterase pharmacohistochemistry and choline acetyltransferase immunohistochemistry
1983, Brain Research BulletinThe topographical distribution of cholinergic cell bodies has been studied in the rat brain and spinal cord by choline acetyltransferase (ChAT)-immunohistochemistry and acetylcholinesterase (AChE)-pharmacohistochemistry using diisopropylfluorophosphate (DFP). The ChAT-containing cells and the cells that stained intensely for AChE 4–8 hr after DFP were mapped in detail on an atlas of the forebrain (telencephalon, diencephalon) hindbrain (mesencephalon, rhombencephalon) and cervical cord (C2, C6). Striking similarities were observed between ChAT-positive cells and neuronal soma that stained intensely for AChE both in terms of cytoarchitectural characteristics, and with respect to the distribution of the labelled cells in many areas of the central nervous system (CNS). In the forebrain these areas include the caudatoputamen, nucleus accumbens, medial septum, nucleus of the diagonal band, magnocellular preoptic nucleus and nucleus basalis magnocellularis. In contrast, a marked discrepancy was observed in the hypothalamus and ventral thalamus where there were many neurons that stained intensely for AChE, but where there was an absence of ChAT-positive cells. No cholinergic perikarya were detected in the cerebral cortex, hippocampus, amygdala and dorsal diencephalon by either histochemical procedure. In the hindbrain, all the motoneurons constituting the well-established cranial nerve nuclei (III–VII, IX–XII) contained ChAT and exhibited intense staining for AChE. Further, a close correspondence was observed in the distribution of labeled neurons obtained by the two histochemical procedures in the midbrain and pontine tegmentum, including the laterodorsal tegmental nucleus, some areas in the caudal pontine and bulbar reticular formation, and the central gray of the closed medulla oblongata. On the other hand, AChE-intense cells were found in the nucleus raphe magnus, ventral part of gigantocellular reticular nucleus, and flocculus of the cerebellum, where ChAT-positive cells were rarely observed. According to both techniques, no positive cells were seen in the cerebellar nuclei, the pontine nuclei, or the nucleus reticularis tegmenti pontis. Large ventral horn motoneurons and, occasionally, cells in the intermediomedial zone of the cervical cord displayed ChAT-immunoreactivity and intense AChE staining. On the other hand, AChE-intense cells were detected in the dorsal portion of the lateral funiculus, but immunoreactive cells were not found in any portion of the spinal cord white matter. The present observations indicate that there is an excellent correspondence, both in terms of distribution and morphology, between ChAT-containing and AChE-intense neurons in most regions of the CNS. AChE pharmacohistochemistry can, therefore, be used as a reliable method to detect cholinergic neurons in many, but not all regions of the CNS. Finally, it is proposed that central cholinergic neurons can be subdivided conveniently into four major cell groups: (1) the rostral column (basal forebrain); (2) the caudal column (pons); (3) local circuit neurons in dopamine-rich regions of the forebrain; and (4) somatic and visceral motoneurons.
Catecholamine varicosities in cat dorsal root ganglion and spinal ventral roots
1983, Brain ResearchCatecholamine (CA) varicosities have been observed within the dorsal root ganglion and spinal ventral roots of the cat at all spinal levels. There was no apparent change in either appearance or numbers of these CA varicosities following spinal transection or distal spinal root lesion. It is suggested that the source of CA innervation of these areas is sympathetic accompanying transdural blood vessels.
The preganglionic sympathetic neurons in the intermediolateral cell column of the thoracic and upper lumbar segments of the spinal cord which innervate the chromaffin cells in the adrenal medulla, sympathoadrenal preganglionic neurons, were identified by the method of retrograde axonal transport of the fluorescent dyes Fast Blue and True Blue. In rats, Fast Blue or True Blue was injected into the medulla of the left adrenal gland. After a survival period of 5 days, the animals were perfusion fixed, the thoracic and lumbar spinal cord sectioned and processed for the immunofluorescent localization of met-enkephalin, neurophysin, oxytocin, serotonin, somatostatin and substance P immunoreactivity.
Neuronal perikarya which were retrogradely-labeled with Fast Blue or True Blue were observed in the intermediolateral cell column from the T1 to the L2 spinal cord segments. The distribution of the sympathoadrenal neurons was determined by counting the number of retrogradely-labeled neurons per spinal cord segment. In the five animals used for quantifying the sympathoadrenal preganglionic neurons, the majority (72.3%) of the retrogradely-labeled neurons counted per spinal cord were located within the T7–T12 segments. The T9 segment contained the largest average number (20.1%) of retrogradely-labeled cells in a single segment.
Met-enkephalin, serotonin and substance P immunoreactive fibers were prominent in the intermediolateral cell column, whereas oxytocin, neurophysin and somatostatin immunoreactive fibers were sparse. The met-enkephalin, serotonin and substance P fibers were seen surrounding both unlabeled and retrogradely-labeled neurons; somatostatin fibers appeared to preferentially contact retrogradely-labeled neurons; whereas, the neurophysin and oxytocin fibers were not found in proximity to retrogradely-labeled neurons.
Met-enkephalin, neurophysin, oxytocin, somatostatin and substance P immunoreactivity were depleted in the intermediolateral cell column below the level of a spinal cord transection. Serotonin immunoreactivity was depleted in the intermediolateral cell column below the level of the transection for five to six segments, but sparse networks of immunoreactive fibers were observed in both the intermedio-lateral cell column and the ventral horn in more caudal segments. Met-enkephalin, serotonin, somatostatin and substance P immunoreactivity were decreased in both the contralateral and ipsilateral intermediolateral cell column below the level of a spinal cord hemisection, suggesting that both crossed and uncrossed descending pathways exist. Neurophysin and oxytocin immunoreactivity were depleted below the level of the hemisection in the ipsilateral intermediolateral cell column without noticeable decrease in the level of immunoreactivity in the contralateral intermediolateral cell column, suggesting that a decussation does not occur at the level of the spinal cord, but may exist above the level of the hemisection.
The sympathoadrenal preganglionic neurons in the intermediolateral cell column of the thoracic and lumbar spinal cord were observed and quantified. The findings suggest that sympathoadrenal preganglionic neurons, as well as other neurons in the intermediolateral cell column, receive met-enkephalin, serotonin and substance P afferents; somatostatin afferents preferentially surround sympathoadrenal neurons; and neurophysin and oxytocin immunoreactive fibers do not appear to impinge upon sympathoadrenal preganglionic neurons.
Innervation of the spinal cord by sympathetic fibers
1980, Experimental NeurologyPharmacologic and neurochemical studies suggest that catecholamines are still present below the level of transection in the spinal cord of the chronic spinal animal, despite the degeneration of bulbospinal catecholamine pathways. Histofluorescence studies of rat and dog spinal cord revealed noradrenergic fibers and varicosities remaining in the chronically decentralized spinal cord which can account for the low concentrations of norepinephrine (NE) found below the transection. The fibers appear to enter the spinal cord with blood vessels through the anterior median fissure, and are probably of sympathetic origin. In the spinal cord, these fibers can dissociate from blood vessels and continue through the neuropil; they are associated with neurons in the ventral horn and occasionally in the central gray. These peripheral sympathetic fibers may influence motor systems and other nervous functions.