Changes in the blood vessels, spinal cord neurocytes, pia mater and spinal ganglia in chronic stimulation of the sympathetic trunks

Taking into account the data concerning disturbances in blood supply of the spinal cord as a response to irritation of the sympathetic trunks, the experimental morphological investigation has been performed on rabbits. By means of the injection technique and staining of neurocytes, changes in the spinal cord, in the spinal nodes and in the pia mater have been studied at chronic irritation of the lumbar nodes of the sympathetic trunk. Certain degenerative changes have been revealed in nervous cells and also phenomena of the spinal cord ischemia, decreasing contacts between the nervous cells and the capillaries surrounding them. As the authors believe, these data can be used by clinicians for revealing pathological mechanisms of the spinal cord ischemia as a result of chronic irritation of the sympathetic trunk.     

Developmental changes of choline acetyltransferase (ChAc) activity in chick embryo spinal and sympathetic ganglia

The ChAc activity of spinal and sympathetic ganglia was measured throughout the embryonic life of the chick. In spinal ganglia, the ChAc activity reached a first peak when the maximal proliferation of neuroblasts occurred. Then, the relative ChAc activity decreased. After the 12th day of incubation, the enzyme activity increased again and reached a second peak on the 16th day. In sympathetic ganglia, the general course of the development of ChAc activity was similar to spinal ganglia. However, higher enzymic activity was found. Furthermore, the earlier peak of ChAc activity occurred 48 hr later than the corresponding peak in spinal ganglia. The behaviour of ChAc activity in these two areas of the developing nervous system is interpreted as a function of their histogenesis.     

Immunohistochemical characterisation of sympathetic and parasympathetic pelvic neurons projecting to the distal colon in the male rat

The pelvic ganglia are mixed ganglia containing both sympathetic and parasympathetic neurons that receive spinal input via the hypogastric (lumbar cord) and pelvic nerves (sacral cord), respectively. A recent study has utilised immunohistochemistry against synaptophysin (a protein associated with small vesicles) to visualise the preganglionic terminals in these ganglia. By selectively cutting the hypogastric or pelvic nerves and allowing subsequent terminal degeneration, the populations of parasympathetic and sympathetic preganglionic terminals, respectively, can be visualised. The present study has used this method in conjunction with retrograde labelling of pelvic neurons from the distal colon and double label immunofluorescence against tyrosine hydroxylase and vasoactive intestinal polypeptide (VIP) to identify and characterise the sympathetic and parasympathetic neurons projecting to the distal colon from the major pelvic ganglia of the male rat. Approximately equal numbers of distal colonic-projecting pelvic neurons are sympathetic and parasympathetic. Almost all noradrenergic neurons are sympathetic. Of the VIP neurons that project to the distal colon approximately one third are sympathetic, one third parasympathetic and the remaining third are possibly innervated by both the lumbar and sacral cord. Extrapolation from our results also suggests that the majority of non-noradrenergic neuropeptide Y neurons (which are known to comprise the remainder of the neurons) are parasympathetic. These studies have demonstrated that the pelvic ganglia are a major source of sympathetic innervation to the distal bowel and have further shown that the distal colon is another target for the non-noradrenergic sympathetic neurons of the pelvic ganglia.     

Extra-organic sources of innervation of the sigmoid]

By means of horseradish peroxidase administration into the wall of the sigmoid colon central part, localization, relative amount, body forms and size of the neurons, dealing with innervation of the given part of the colon have been determined. Labelled neurons are present in the colon wall, in ganglia of the caudal mesenteric artery nervous plexus, in the caudal and cranial mesenteric ganglia in the celiac plexus ganglia, in nodes and internodal branches of the lumbar part of the sympathetic trunk (the left one predominantly) and in the spinal ganglia from TXIII up to LVII. In the grey substance of the spinal cord labelled neurons are not revealed. The main part of the postganglionar sympathetic neurons, projecting their axons to the sigmoid colon, are situated in the caudal mesenteric ganglion. In the spinal ganglia the most part of the labelled neurons are to the left at the level of LII-LVI, to the right--at the level of LII-LV. The optimal time for revealing the greatest number of the labelled neurons are the 1st-3d days after administration of the enzyme. Capture of the lable takes place later in the neurons of those ganglia, which are situated more further from the place of peroxidase administration.     

Location of efferent sympathetic neurons and afferent neurons in spinal ganglia innervating the heart

Location and numbers of neurons associated with sympathetic innervation of the heart within the right stellate and accessory cervical ganglia, the spinal cord, and spinal ganglia were investigated using horseradish peroxidase retrograde axonal transport techniques in cats. The enzyme was applied to central sections of the anastomosis of the stellate ganglion with the vagus nerve, the inferior cardiac nerve, and the vagosympathetic trunk caudal to the anastomosis. Labeled neurons within the stellate ganglion were located close to the point of departure of the nerves and more thinly distributed in the accessory cervical ganglion. A group of labeled cells was found in the anastomosis itself. Preganglionic neurons associated with sympathetic innervation of the heat were detected at segmental levels T₁–T₅ in the spinal cord. Labeled neurons were diffusely located in the spinal ganglia, concentrated mainly at levels T₂–T₄.Medical Institute, Ministry of Public Health of the RSFSR, Yaroslavl'. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 106–111, January–February, 1989.     

Distribution of arginine-vasopressin in the trigeminal,dorsal root ganglia and spinal cord of the rat; depletion by capsaicin

We have measured arginine vasopressin in the neural lobe, the trigeminal ganglion (TG), dorsal root ganglia (DRG), spinal cord, trigeminal and sciatic nerves of the rat by radioimmunoassay. In control rats, the neural lobe contained 1600 pg/mg, the ganglia 52.5, 21.0, 8.5, 4.28, 3.85 pg/mg in the lumbar, sacral, cervical, thoracic, and trigeminal ganglion, respectively, the spinal cord contained 5.1, 4.3, 4.2 and 2.6 pg/mg in the lumbar, thoracic, sacral and cervical cord, respectively and the trigeminal and sciatic nerves contained 3.8 and 13 pg/mg. Neonatal capsaicin treatment depleted about 38–67% of AVP in the ganglia. Residual AVP amounted to 526.8, 30.55, 20.75, 12.88, 4.95, 2.74, 2.14, 7.94 and 2.53 pg/mg in the neural lobe, lumbar, thoracic, sacral, cervical DRG, lumbar, thoracic spinal cord, the sciatic and trigeminal nerves respectively. Capsaicin destroyed about 40.5% of total cells and 52% of AVP-immunoreactive neurons.     

Differential effects of denervation on acetylcholinesterase activity in parasympathetic and sympathetic ganglia of the frog, Rana pipiens

The transsynaptic regulation of acetylcholinesterase (AChE) was studied by recording the changes in enzymatic activity following denervation in two types of autonomic ganglia in the frog, Rana pipiens. Opposite effects on AChE were found in the parasympathetic cardiac ganglion and in the sympathetic lumbar ganglion; denervation produced a significant increase in AChE activity in cardiac ganglia but a significant decrease in lumbar ganglia. The relative effects of denervation on intracellular and total AChE were examined by selectively inhibiting extracellular AChE with echothiophate, a poorly lipid-soluble cholinesterase inhibitor. Denervation resulted in a significant increase in intracellular AChE in cholinergic cardiac ganglia but had no effect on intracellular AChE activity in adrenergic lumbar ganglia. Histochemical studies revealed little change in extracellular AChE staining upon denervation in the cardiac ganglion, whereas in the lumbar ganglia there was a loss of AChE-specific reaction product. These results raise the possibility that the transsynaptic control of AChE activity by innervation in the frog is influenced by the transmitter synthetic properties of the postsynaptic ganglion cells.     

Cyclic AMP content of autonomic ganglia as affected by catecholamines

The relative content of cAMP was measured in the rat ganglion nodosum, lumbar ganglia of the sympathetic trunk, the main pelvic ganglion and intramural ganglia of the heart. It was observed that the basal level of cAMP in the cardiac ganglia was lower than in other ganglia. The process of stimulation of the cAMP content by noradrenaline was most pronounced in the main pelvic and lumbar ganglia, that by dopamine in the cardiac ganglia. The catecholamines failed to alter the cAMP content in the ganglion nodosum.     

Effects of corticospinal tract stimulation on renal sympathetic nerve activity in rats with intact and chronically lesioned spinal cords

Sympathetic preganglionic neurons and interneurons are closely apposed (presumably synapsed upon) by corticospinal tract (CST) axons. Sprouting of the thoracic CST rostral to lumbar spinal cord injuries (SCI) substantially increases the incidence of these appositions. To test our hypothesis that these additional synapses would increase CST control of sympathetic activity after SCI, we measured the effects of electrical stimulation of the CST on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in alpha-chloralose-anesthetized rats with either chronically intact or chronically lesioned spinal cords. Stimuli were delivered to the CST at intensities between 25-150 muA and frequencies between 25 and 75 Hz. Stimulation of the CST at the midcervical level decreased RSNA and AP. These decreases were not mediated by direct projections of the CST to the thoracic spinal cord because we could still elicit them by midcervical stimulation after acute lesions of the CST at caudal cervical levels. In contrast, caudal thoracic CST stimulation increased RSNA and AP. Neither the responses to cervical nor thoracic stimulation were affected by chronic lumbar SCI. These data show that the CST mediates decreases in RSNA via a cervical spinal system but excites spinal sympathetic neurons at caudal thoracic levels. Because chronic lumber spinal cord injury affected responses evoked from neither the cervical nor thoracic CST, we conclude that lesion-induced or regeneration-induced formation of new synapses between the CST and sympathetic neurons may not affect cardiovascular regulation.     

Specificity of nerve fibre 'attraction' to autonomic effector organs in tissue culture.

Explants of atrium, vas deferens and lung from 5-day-old rats were grown between, and 1–2 mm from, a row each of sympathetic ganglia and spinal cord explants. After 5 days the amount of sympathetic nerve fibre growth in cultures with atrium or vas deferens (but not lung) was greater than in controls and directed towards the tissues. In contrast, in cultures with atrium, vas deferens and lung, the direction and amount of nerve growth from spinal cord explants was not significantly different from controls. Further, when sympathetic ganglia were grown between, and 1–2 mm from, a row each of atrium and ventricle explants, the total amount of nerve growth was increased and directed mainly towards the atrium. The results are discussed in relation to the hypothesis that normally densely innervated autonomic effector organs contain higher levels of Nerve Growth Factor than tissues which become more sparsely innervated, and that this allows nerve fibres from sympathetic ganglia (but not NGF-insensitive spinal cord) to distinguish between different tissues from a distance.     

Peripheral and central origin of Phe-Met-Arg-Phe-amide immunoreactivity in rat spinal cord

Phe-Met-Arg-Phe-amide immunoreactivity (FMRF-NH2-IR) is highly concentrated in the dorsal horn of rat spinal cord, and particularly in nerve terminals of lamina I. In order to establish the location of the cell bodies of the lamina I terminals containing FMRF-NH2-IR, we measured by radioimmunoassay the FMRF-NH2-IR in sensory ganglia and in spinal roots. FMRF-NH2-IR was found in both tissues, and reverse-phase HPLC analysis revealed that both tissues contain the same molecular forms that are also present in the spinal cord. Lumbo-sacral rhizotomy induced a 50% decrease of FMRF-NH2-IR in the lumbar segment of the spinal cord suggesting that at least a portion of the FMRF-NH2-IR present in this tissue is of peripheral origin. Transection of the spinal cord at the midthoracic level induced a 20-50% decrease of FMRF-NH2-IR in the lumbar segment of the spinal cord suggesting also the presence of FMRF-NH2-IR in descending pathways.     

Consequences of neural tube and notochord excision on the development of the peripheral nervous system in the chick embryo

Notochordectomy and neuralectomy were carried out either in one- or in two-step experiments on the chick embryo. The aim of this operation was to study the influence of the axial organs (notochord and neural tube) on the development of the ganglia of the peripheral nervous system. The neural crest cells from which most peripheral ganglion cells arise were labeled through the quail-chick marker system and their fate was followed under various experimental conditions. It appeared that the development of the dorsal root and sympathetic ganglia depends on survival and differentiation of somite-derived structures. In the absence of neural tube and notochord, somitic cells die rapidly, and so do the neural crest cells that are present in the somitic mesenchyme at that time. In contrast, those crest cells which can reach the mesenchymal wall of the aorta, the suprarenal glands, or the gut survive and develop normally into nerve and paraganglion cells. Differentiation of the neural crest- and placode-derived sensory ganglia of the head which develop in the cephalic mesenchyme is not affected by removal of notochord and encephalic vesicles. These results show that the peripheral ganglia are differentially sensitive to the presence of the neural tube and the notochord. Among the various ganglia of the peripheral nervous system, spinal and sympathetic ganglia are the only ones which require the presence of these axial structures. The neural tube allows both the spinal and the sympathetic ganglia to develop in the absence of the notochord. In contrast, if the notochord is left in situ and the neural tube removed, the spinal ganglia fail to differentiate and only sympathetic ganglia can develop.     

Nerve growth factor changes the relative levels of neuropeptides in developing sensory and sympathetic ganglia of the chick embryo

The effects of chronic nerve growth factor administration on the development of neuropeptides in the embryonic chick peripheral nervous system were quantitated by radioimmunoassays. Starting at embryonic Day 3.5, daily doses of 20 micrograms of nerve growth factor (NGF) increased the substance P content of lumbosacral spinal sensory ganglia at all ages studied (Days 10-14), while having no effect on substance P levels of thoracic sensory ganglia. In contrast, the contents of somatostatin were increased in both thoracic and lumbosacral ganglia, but only at comparatively late time points (Day 14). Nerve growth factor administration was also found to decrease the somatostatin contents of lumbosacral paravertebral sympathetic ganglia at early time points (Day 8) while increasing levels at later stages (Day 14), thus acting to accelerate the normally occurring developmental changes in level of this peptide. These changes were shown to be specific for somatostatin by demonstrating that NGF increased tyrosine hydroxylase levels in sympathetic neurons at Day 8, and had no effect on sympathetic vasoactive intestinal polypeptide levels at Day 14. It has been concluded that exogenous NGF does not simply act to increase or prolong the expression of neuron-specific phenotypes in the chick, but rather its action is time and location dependent to accelerate development.     

Descending course of primary afferent collaterals in the cat's spinal cord.

After injecting horseradish-peroxidase into the lower thoracic, lumbar and sacral spinal cord segments of cats, labelled perikarya were found in several spinal ganglia localized cranially to the site of injection. The segmental distance between the injection site and the rostralmost localized ganglion with labelled cells varied depending on the medio-lateral localization of the injection. The longest distance (10 segments) was achieved by medial injections. Primary sensory neurones with long descending collaterals belong to large ganglion cells.     

Biomechanical implications of lumbar spinal ligament transection

Many lumbar spine surgeries either intentionally or inadvertently damage or transect spinal ligaments. The purpose of this work was to quantify the previously unknown biomechanical consequences of isolated spinal ligament transection on the remaining spinal ligaments (stress transfer), vertebrae (bone remodelling stimulus) and intervertebral discs (disc pressure) of the lumbar spine. A finite element model of the full lumbar spine was developed and validated against experimental data and tested in the primary modes of spinal motion in the intact condition. Once a ligament was removed, stress increased in the remaining spinal ligaments and changes occurred in vertebral strain energy, but disc pressure remained similar. All major biomechanical changes occurred at the same spinal level as the transected ligament, with minor changes at adjacent levels. This work demonstrates that iatrogenic damage to spinal ligaments disturbs the load sharing within the spinal ligament network and may induce significant clinically relevant changes in the spinal motion segment.     

Nerve growth factor-induced stimulation of dorsal root ganglion/spinal cord co-grafts in oculo: enhanced survival and growth of CGRP-immunoreactive sensory neurons

Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted beside the spinal cord graft. Nerve growth factor or vehicle was injected weekly for 4 weeks into the anterior eye chamber. Co-grafts were examined weekly and, at 6 weeks, processed for calcitonin gene-related peptide (CGRP) immunofluorescence. No differences in overall size were determined for the grafts. Co-grafts treated with nerve growth factor contained many more CGRP neurons (19.4 cells/20 microm) that were significantly larger (mean 764 microm2) than neurons from control co-grafts (8.6 cells/20 microm; mean 373 microm2). In co-grafts treated with nerve growth factor, CGRP-immunoreactive fibers were extensive in the dorsal root ganglion, adjacent iris, and spinal cord compared to control co-grafts. A few CGRP-positive motoneurons were observed in the spinal cord, but no differences in number or size of motoneurons were found. The current report demonstrates that spinal cord and dorsal root ganglia can be co-grafted in oculo for long periods of time. Many dorsal root ganglion neurons survive and send peripheral processes into the iris and central processes into the spinal cord under the influence of exogenous nerve growth factor. The intraocular graft paradigm can be of use to further examine the role of neurotrophic factors in regulating or modulating dorsal root ganglion and spinal cord neurons.     

DEVELOPMENTAL CHANGES OF CHOLINESTERASES AND MONOAMINE OXIDASE IN CHICK EMBRYO SPINAL AND SYMPATHETIC GANGLIA

Abstract— Total cholinesterase, acetylcholinesterase, (AChE) and monoamine oxidase (MAO) activity and protein content were determined throughout the embryonic life of the chick in spinal and sympathetic ganglia. The greatest part of total cholinesterase activity was due to AChE.
AChE and MAO activity increased in both spinal and sympathetic ganglia very similarly from the 6th to the 12th day of incubation; from this day on a significant divergence occurred, mainly owing to a steady fall in spinal ganglion AChE, which decreased to approximately one tenth of the maximum value. The ratio of MAO activity in sympathetic and spinal ganglia increased from the 8th day onwards and approached 5·0 at hatching. The ratio between sympathetic and spinal ganglia, for AChE, choline acetylase (ChAc) and MAO activity, suggests a relationship between the maturation of the synapse in the sympathetic ganglia and the maximal activity of these enzymes.     

Ependyma and meninges of the spinal cord of the mouse

Summary In addition to ependymal epithelial cells, numerous tanycytes are found along the entire central canal of the mouse. These tanycytes are arranged in clusters in the cervical, thoracic and lumbar segments of the spinal cord. In the conus medullaris, tanycytes separate and ensheath bundles of myelinated and unmyelinated axons; their processes take part in the formation of the stratum marginale gliae. In the caudal part of the spinal cord, the ventral wall of the central canal is thin and some areas are reduced to a single-cell thickness. In this region, ependymal cells participate directly in the formation of the stratum marginale gliae.The meninges consist of the intima piae, the pia mater, the arachnoid, a subdural neurothelium and the dura mater. The subarachnoid space appears occluded and opens only around the spinal roots. In the vicinity of the spinal ganglia, the dura mater, the subdural neurothelium and the arachnoid form a cellular reticulum.     

Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation

The peripheral branch of primary sensory neurons regenerates after injury, but there is no regeneration when their central branch is severed by spinal cord injury. Here we show that microinjection of a membrane-permeable analog of cAMP in lumbar dorsal root ganglia markedly increases the regeneration of injured central sensory branches. The injured axons regrow into the spinal cord lesion, often traversing the injury site. This result mimics the effect of a conditioning peripheral nerve lesion. We also demonstrate that sensory neurons exposed to cAMP in vivo, when subsequently cultured in vitro, show enhanced growth of neurites and an ability to overcome inhibition by CNS myelin. Thus, stimulating cAMP signaling increases the intrinsic growth capacity of injured sensory axons. This approach may be useful in promoting regeneration after spinal cord injury.     

Effects of Peripheral Axotomy on Cholecystokinin Neurotransmission in the Rat Spinal Cord

Abstract : Because cholecystokinin (CCK) acts as a "functional" endogenous opioid antagonist, it has been proposed that changes in central CCKergic neurotransmission might account for the relative resistance of neuropathic pain to the analgesic action of morphine. This hypothesis was addressed by measuring CCK-related parameters 2 weeks after unilateral sciatic nerve section in rats. As expected, significant decreases (-25-38%) in the tissue concentrations and in vitro release of both substance P and calcitonin gene-related peptide were noted in the dorsal quadrant of the lumbar spinal cord on the lesioned side. In contrast, the tissue levels and in vitro release of CCK were unchanged in the same area in lesioned rats. Measurements in dorsal root ganglia at L4-L6 levels revealed no significant changes in proCCK mRNA after the lesion. However, sciatic nerve section was associated with a marked ipsilateral increase in both CCK-B receptor mRNA levels in these ganglia (+70%) and the autoradiographic labeling of CCK-B receptors by [³H]pBC 264 (+160%) in the superficial layers of the lumbar dorsal horn. Up-regulation of CCK-B receptors rather than CCK synthesis and release probably contributes to increased spinal CCKergic neurotransmission in neuropathic pain.