Rolando Substance Research Articles

Distribution of astrocytes in the lumbosacral spinal cord and the effect of epidural anaesthesia

Event Abstract Back to Event Distribution of astrocytes in the lumbosacral spinal cord and the effect of epidural anaesthesia Ferenc Hajos1 and Balázs Gerics1* 1 Szent Istvan University , Department of Anatomy & Histology, Hungary The GFAP-map of the spinal cord is very fragmentary. The aim of the present study was to give a more detailed account on the distribution of GFAP-IR astrocytes in the lumbosacral spinal cord. In all segments of the serial Vibratome-sections an intense immunostaining was observed in the Rolando substance of the dorsal horn and around the large ventral horn motor neurons. While immunoreactive astrocytes of the Rolando substance proved to be densely packed small cells with short stout processes other areas of the dorsal horn contained delicate, stellate astrocytes with long, slender processes. In the ventral horn, the large motor neurons were contacted by immunoreactive astrocytes. Characteristically, in the upper lumbar segments where motor neurons occurred in two groups the focus of immunoreactivity was also doubled. The central grey matter had a slightly higher immunoreactivity than its surrounding. An intense staining was observed around the central canal which proved to be due to immunoreactive subependymal cells rather than to the ependyma proper. In the white matter marked difference was observed in the radially fibrous and cellular appearences of GFAP in the ventral and lateral, and the dorsal funiculus, respectively. Thirty minutes after the epidural deposition of 1% lidocain a substantial enhancement of GFAP immunoreactivity was observed in the Rolando substance. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - non-degenerative disorders Citation: Hajos F and Gerics B (2009). Distribution of astrocytes in the lumbosacral spinal cord and the effect of epidural anaesthesia. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.029 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Feb 2009; Published Online: 26 Feb 2009. * Correspondence: Balázs Gerics, Szent Istvan University, Department of Anatomy & Histology, Budapest, Hungary, gerics.balazs@aotk.szie.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ferenc Hajos Balázs Gerics Google Ferenc Hajos Balázs Gerics Google Scholar Ferenc Hajos Balázs Gerics PubMed Ferenc Hajos Balázs Gerics Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.

Light and electron microscopic localization of B-50 (GAP43) in the rat spinal cord during transganglionic degenerative atrophy and regeneration.

Crush or transection of a peripheral nerve is known to induce transganglionic degenerative atrophy (TDA) in the segmentally related, ipsilateral Rolando substance of the spinal cord. When the lost peripheral connectivity is reestablished, the consecutive regenerative synaptoneogenesis results in restoration of the circuitry in the formerly deteriorated upper dorsal horn. Enhanced expression of the growth-associated protein (GAP43) B-50 occurs during neuronal differentiation, axon outgrowth, and peripheral nerve regeneration. This study documents changes in immunocytochemical distribution of B-50 in the regions of the lumbar spinal cord which are segmentally related to the axotomized sciatic nerve. At the light microscopic level, a weak B-50 immunoreactivity (BIR) is present in the neuropil of the upper dorsal horn of control animals. After unilateral transection and ligation of the sciatic nerve, BIR increased in the ipsilateral upper dorsal horn at 17 days postinjury, but decreased again after 24 days with respect to the contralateral side. Differences between effects of crush and transection were prominent in combined crush-cut experiments as well (i.e., after unilateral crush and contralateral transection and ligation of the sciatic nerve). Electron microscopic studies show that in the uninjured and injured spinal cord, BIR is detected in axons and axon terminals, but not all are stained. After transection of the sciatic nerve, BIR is found in afflicted primary sensory axon terminals, including those contacting substantia gelatinosa neurons and in axon terminals undergoing glial phagocytosis. The localization of BIR seen after crushing the sciatic nerve is similar. However, at 24 days after crush, BIR is detected also in axonal growth cones. In the ventral horn of control animals, synaptic boutons impinging upon motor neurons exhibited weak BIR. At 17 days after unilateral transection of the sciatic nerve, the pericellular BIR surrounding motor neurons is decreased at the ipsilateral with respect to the contralateral side, whereas 24 days after crush injury it increased considerably. Our results show that peripheral nerve injury inducing TDA also affects BIR distribution in the spinal gray matter. Successful regeneration of the peripheral nerve after crush lesion is associated with enhanced expression of B-50 in growth cones of sprouting central axons. The neuroplastic response of B-50 is in line with a function of B-50 in axonal sprouting and reactive synaptogenesis.

Transneuronal degeneration in the Rolando substance of the primate spinal cord evoked by axotomy-induced transganglionic degenerative atrophy of central primary sensory terminals.

Transection of the sciatic nerve in Rhesus monkeys and the consequent transganglionic degenerative atrophy (TDA) of central terminals of primary afferents result in transneuronal degeneration of substantia gelatinosa (SG) cells. Severe degeneration is characterized by an increased electron density of the nucleus and by conspicuous shrinkage of the cytoplasm, mitochondrial swelling, dilation of cisterns of the rough-surfaced endoplasmic reticulum, accumulation of free ribosomes and an electron-dense material in the cytoplasm. In the mild form, dilation of cisternal elements of the endoplasmic reticulum, swollen mitochondria and accumulation of free ribosomes takes place. About 10% of SG cells in segment L5 undergo the severe form whereas the rest shows signs of the mild form. Cytoplasmic alterations that occur during transneuronal degeneration seem to start at the level of subsurface cisterns. Dendrites and axons of transneuronally degenerating SG cells also show a conspicuous electron density. By analyzing the synaptic relationships of such "darkened" dendrites, connections in the upper dorsal horn can be deciphered. Modular units of the primary nociceptive analyzer that evaluate noxious and innocuous inputs on the basis of thin versus thick (A delta C/A beta) afferent activity and subjecting them to descending control appear to be recruited from structurally dispersed elements of synaptic glomeruli. These are arranged alongside dendritic processes of large antenna cells which relay impulses to projection cells of the spinothalamic tract.

Distribution of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the rat brain. II. Mesencephalon, rhombencephalon and spinal cord.

The topographical mapping of glial fibrillary acidic protein (GFAP)-immunoreactivity was performed in coronal serial sections of the rat mesencephalon, rhombencephalon and spinal cord. Relative to a background of poor or moderate overall staining of the mesencephalon, the interpeduncular nucleus, substantia nigra and the periaqueductal grey matter were prominent by their intense GFAP-immunoreactivity. The pons and particularly the medulla contained more GFAP-labelled elements compared with the mesencephalon. The spinal trigeminal nucleus and Rolando substance were distinguished by their intense staining. Large fibre tracts were usually poor in immunoreactive GFAP. In a concluding discussion, findings relevant to the GFAP-mapping of the whole rat CNS are evaluated with regard to possible reasons underlying the observed differential distribution of GFAP-immunoreactivity.

Cobalt-complex ATP enhanced regeneration in the dorsal horn of the rat spinal cord.

ATP, the energy source for axoplasmic transport, is indispensable for the transport of nerve growth factor (NGF). NGF regulates the regeneration of central processes of the primary sensory neurons, by means of transganglionic regulatory mechanisms. This central regeneration was investigated with the help of the histochemical detection of fluoride-resistant acid phosphatase (FRAP), one of the marker enzymes of the primary nociceptive neurons. Transganglionic degenerative atrophy (TDA) of the central terminals of primary sensory neurons was induced with sciatic nerve crush. Dynamics of central regeneration was studied in rats treated with a cobalt-ATP complex, and with commercially available Na-ATP, respectively, by means of histochemical detection of the restitution of FRAP activity in the Rolando substance. Disappearance of FRAP activity was complete on the 6th postoperative day in the medial two-thirds of the upper dorsal horn in segments L2-L6. The regeneration (i.e. replenishment of FRAP activity) began on the 14th day and was complete by the 31st day in animals treated with cobalt-ATP, while in the animals treated with Na-ATP the replenishment of FRAP activity began on the 20th day and was complete only by the 60th day. It is concluded that the cobalt-ATP-complex significantly enhances central regeneration.

Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor (NGF)

Blockade of axonal transport or transection of the rat sciatic nerve results in transganglionic degenerative atrophy (TDA) of nerve terminals containing fluoride-resistant acid phosphatase (FRAP) in the Rolando substance of the spinal cord. Application of vinblastine (9 μg) in a cuff around the sciatic nerve of adult rats blocked the retrograde transport of [ 125I]NGF in sensory fibers; this amount of vinblastine is identical to the threshold amount that induces TDA. Conversely, application of NGF to the proximal stump of the transected sciatic nerve prevented or delayed the occurrence of TDA as reflected by the maintenance of FRAP in the upper dorsal horn, that otherwise would inevitably disappear following the peripheral nerve lesion. These results suggest that endogenous NGF transported retrogradely in peripheral sensory fibers of the adult rat under normal conditions may be responsible for the regulation of the structural and functional integrity of the central terminals of these FRAP-containing primary sensory neurons and that TDA may be the consequence of the failure of NGF to reach the perikarya of these neurons.

Treatment of chronic pain syndromes with iontophoresis of vinca alkaloids to the skin of patients

Repeated iontophoretic administration of the microtubule inhibitors vinblastic or vincristine to the segmentally related dermatomes of patients suffering from postherpetic, trigeminal and other neuralgias permanently alleviates chronic, autochthonoue pain. The beneficial effect of this therapy is probably due to transganglionic degenerative atrophy of primary central sensory terminals in the Rolando substance by blockade of retrograde axoplasmic transport in sensory nerves.

Reversibility of microtubule inhibitor-induced transganglionic degenerative atrophy of central terminals of primary nociceptive neurons

Microtubule inhibitor Vinca alkaloids applied around a peripheral nerve induce transganglionic degenerative atrophy of the central terminals of primary nociceptive neurons. This effect is reversible: 40–50 days later the original histochemical structure of the central terminals is restored. Restoration of fluoride-resistant acid phosphatase activity (the marker enzyme of primary nociceptive neurons) in the Rolando substance is due to regenerative sprouting of the formerly atrophied central terminals. Since peripherally-applied Vinca alkaloids induce transganglionic degenerative atrophy of the central terminals without inducing Wallerian degeneration of the peripheral nerve, and since this effect (virtually a synaptic discoupling) is only temporary, this approach may be used in the treatment of otherwise intractable neuralgias without inducing irreparable alterations.

Regenerative synaptoneogenesis in the Mammalian spinal cord: dynamics of synaptochemical restoration in the Rolando Substance after transganglionic degenerative atrophy.

Crush injury of the sciatic nerve, that results in Wallerian degeneration of axons in the peripheral stump, induces, within 10-14 days, transganglionic degenerative atrophy of central terminals of primary nociceptive neurons in the ipsilateral substantia gelatinosa Rolandi of the segmentally related region of the spinal cord. Transganglionic degenerative atrophy is characterized by disappearance of fluoride-resistant acid phosphatase (FRAP) from the Rolando substance, normally exerted by primary nociceptive terminals. From the 40th postoperative day on, FRAP reaction starts to reappear in the formerly depleted Rolando substance. Restoration of FRAP reactivity reflects regenerative sprouting of formerly atrophied primary nociceptive terminals. Growth cones of primary nociceptive axons establish synapses with dendritic growth cones of substantia gelatinosal gelatinosal cells. Synaptoneogenesis in the Rolando substance follows medio-lateral and caudo-rostral gradients.

Selective ‘labelling’ by transsynaptic degeneration of substantia gelatinosal cells: An attempt to decipher intrinsic wiring in the Rolando substance of primates

Transganglionic degenerative atrophy of primary sensory terminals in the head of the spinal dorsal horn that follows transection of the segmentally related peripheral sensory nerve, induces transsynaptic degeneration of substantia gelatinosal (SG) cells, as was studied here in monkeys. On the basis of increased electron density as a selective ‘labelling’, SG cells are shown to be postsynaptic both to thin (Aδ and C) and to thick (Aβ) afferents as well as to descending (or propriospinal) fibres, while their recurrent axon collaterals establish inhibitory synapses upon somata of neighbouring SG cells and upon Aβ terminals. SG cells are envisaged as biasing elements with a contract-enhancing function that, by means of inhibitory dendro-dendritic and axo-axonal synapses, realize a gating mechanism.

Regional distribution of acid phosphatase-positive axonal systems in the rat spinal cord and medulla, representing central terminals of cutaneous and visceral nociceptive neurons.

In addition to the substantia gelatinosa Rolandi, acid phosphatase active axonal systems are described (1) in the viscerosensory nucleus of the vagus nerve, (2) in Lissauer's band, (3) in the fasciculus cornus posterioris (Cajal), and (4) in the nucleus basilaris externus (Cajal). Electron microscopically, acid phosphatase is located in between synaptic vesicles of axon terminals; the vesicle population of such terminals in the Rolando substance, however, markedly differs from that in systems 1--4, characterized by the presence of large dense-core vesicles. While acid phosphatase-active axon terminals in the Rolando substance appear to subserve cutaneous nociception, circumstantial evidence suggests participation of systems 1--4 in processing visceral nociception.

Degenerative atrophy of central terminals of primary sensory neurons induced by blockade of axoplasmic transport in peripheral nerves.

Perineural colchicine- or vinblastine-treatment results in disappearance of non-lysosomal acid phosphatase activity, characterizing axon terminals in the Rolando substance of the normal spinal cord. Ultrastructural alterations are identical with those seen in the course of degenerative atrophy.

Effect of peripheral anatomy on the fine structure and histochemistry of the Rolando substance: degenerative atrophy of central processes of pseudounipolar cells.

Disappearance of fluorid-resistant acid phosphatase activity from the ipsilateral Rolando substance after transection of the peripheral nerve, is shown to be due to the cessation of enzyme supply from dorsal root ganglion cells to their central terminals. This is accompanied by (or ensues in consequence of) a fine structural derangement of these terminals ("degenerative atrophy"). Fine structural alterations of axon terminals undergoing degenerative atrophy, though similar to some extent to those seen during early phases of a Wallerian degeneration, are markedly different. Also myelinated nerve fibers, both in the dorsal horn and in dorsal columns, are affected by degenerative atrophy. This important, new trophical feature of sensory ganglion cells suggests a delicate metabolic balance between peripheral and central axonal branches of bipolar (pseudounipolar) cells. Degenerative atrophy raises serious implications in evaluating hodological experiments based upon Wallerian degeneration and offers new perspectives for theoretical and clinical neurology.

Representation of cutaneous afferents by fluoride-resistant acid phosphatase (FRAP)-active terminals in the rat substantia gelatinosa rolandi.

While transection of the sciatic nerve results in a complete ipsilateral extinction of FRAP activity in respective segments of the rat spinal cord, cutaneous denervation of the hind leg induces a patchy disappearance of this same enzyme in the Rolando substance. The possible participation of FRAP in metabolism of the primary sensory transmitter substance, its relation to substance P and its involvement in gating mechanisms are discussed.

Fine structure and fluoride resistant acid phosphatase activity of electron dense sinusoid terminals in the substantia gelatinosa Rolandi of the rat after dorsal root transection.

Fluoride resistant acid phosphatase (FRAP) activity of the rat substantia gelatinosa Rolandi is confined to electron dense sinusoid terminals under normal conditions. Transection of dorsal roots or removal of dorsal root ganglia results in a rapid degeneration of more than half of the electron dense sinusoid axon terminals. First signs of degeneration ensue 20 hours after surgery; at the 24 hours state osmiophilic degeneration bodies develop that are translocated into glial elements in the course of the second postoperative day. At the same time, light microscopically visible FRAP-activity of the Rolando substance disappears. Electron histochemical investigations reveal that decreased enzyme activity is due to degeneration of FRAP-positive terminals. It is concluded that FRAP-positive terminals, representing the majority of electron dense sinusoids in the Rolando substance, are dorsal root collaterals; the origin of non-degenerating FRAP-negative electron dense terminals remains unknown for the time being.

Extra-lysosomal localization of acid phosphatase in the spinal cord of the rat.

The Rolando substance of the rat spinal cord was investigated by means of standard electron microscopy and by light-and electron microscopic histochemical demonstration of acid phosphatase. In accordance with previous studies, electron dense, large sinusoid terminals in the Rolando substance, constituting the central element of Rolando glomeruli, are shown to establish numerous axo-axonal and axo-dendritic synapses. Acid phosphatase reaction of the Rolando substance, resistant to 0.2 mM sodium fluoride inhibition, is located in and around the large sinusoid terminals. By using various incubation parameters and cryo-protection, the most plausible physiological localization of this enzyme, probably related to transmission processes appears to be in the greater membrane (glycocalyx) of large sinusoid terminals.