References of "Koulchitsky, Stanislav"
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See detailEffect of Amphetamine on Ventral Tegmental Area Neurons in awake Rats
Delairesse, Charlotte ULiege; Koulchitsky, Stanislav ULiege; Seutin, Vincent ULiege

Poster (2018, December 18)

Amphetamine (AMPH) is an addictive psychostimulant targeting the dopamine system. But its effect on the neurons of this system is still unclear. Here, we studied the effects of amphetamine on the firing ... [more ▼]

Amphetamine (AMPH) is an addictive psychostimulant targeting the dopamine system. But its effect on the neurons of this system is still unclear. Here, we studied the effects of amphetamine on the firing rate of dopamine (DA) and non-dopamine neurons of the ventral tegmental area, a key structure in the reward circuit, of awake rats. Using wireless neural probes to investigate the electrical activity of the neurons in freely moving rats, we observed that acute injection of AMPH is followed by a decrease of firing rate of most of registered DA units. The remaining population of DA units either increased or did not significantly change their activity. At the same time, AMPH stimulated the locomotor activity and induced a stereotypic behavior. (FR) L'amphétamine (AMPH) est un psychostimulant addictif visant le système dopaminergique. Cependant, ses effets sur les neurones de ce système sont nébuleux. Nous étudions les effets de l'AMPH sur la fréquence de décharge des neurones dopaminergiques et non dopaminergique de l'aire tegmentale ventrale, une structure clef du circuit de la récompense, de rats éveillés. En utilisant un système d'électrodes sans fil pour étudier l'activité électrique des neurones de rats libres de leurs mouvements, nous avons observer que l'injection aiguë d'AMPH est suivie d'une diminution de la fréquence de décharge de la majorité des neurones dopaminergiques enregistrés. Le reste des neurones dopaminergique présentaient une activité augmentée ou qui ne subissait pas de changement significatif. En même temps, l'AMPh stimule l'activité locomotrice et induit un comportement stéréotypé. [less ▲]

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See detailSomatotopic principle of perineural implantation of stem cells in patients with brain injuries
Shanko, Yuri; Navitskaya, Valeria; Zamaro, Alexandra et al

in Journal of Neurology and Stroke (2018), 8(5), 259-261

Background: Neuro destructive processes of any etiology are related to problematic and socially important diseases due to ineffective therapeutic strategy and need to search for new successful ways of ... [more ▼]

Background: Neuro destructive processes of any etiology are related to problematic and socially important diseases due to ineffective therapeutic strategy and need to search for new successful ways of treatment and rehabilitation of patient with cerebral infarctions and brain attacks Aims: Authors plant overify hypothesis on viability of additional use of perineural implantation of autologous mesenchymal stem cells (MSC) in order to optimize standard therapy of patients with brain attacks. Such combined technology is aim datextra activation of brain plasticity mechanisms during development of neuro destructive processes. Methods: The technique of MSC perineural migration to injured brain regions was experimentally verifed on rats (n=40) paying attention to somatotopic organization of cranial nerves. This technique was clinically tested in pilot project. Phenotyping of autologous MSC from adipose tissue (AT) was performed in 23 patients with brain attacks. These 23 patients received standard treatment as per international guidelines together with three perineural implantations of autologous MSC from AT with 5-9days intervals. The other group of patients (n=7) received only standard therapy as per international guidelines. Results: Additional use of cell therapy resulted in more rapid and effective recovery of disordered neurological functions in all cases compared to those who received standard therapy. The phenomenon of abrupt recovery of neurological functions was established during frst 24hours after each injection of autologous MSC. Cumulative recovery of functions progressed after each implantation. Discussion and conclusion: Experimentally developed technique of perineural implantation of autologous MSC was successfully verifed in clinical conditions in accordance with certifed cell therapy guideline (The Ministry of Health of the Republic of Belarus) in combination with standard treatment of patients with cerebral infarctions. Cell therapy with autologous MSC from AT by means of perineural delivery to injured brain regions is the basis for activation of reparative potential of nerve tissue and progressive recovery of neurological functions in patients with cerebral infarctions. [less ▲]

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See detailEffect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus
Fischer, Michael; Schmidt, Jakob; Koulchitsky, Stanislav ULiege et al

in Journal of Headache and Pain (2018), 19(1), 3

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from ... [more ▼]

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception. METHODS: In a rat model of meningeal nociception, single cell activity of neurons in the spinal trigeminal nucleus with meningeal afferent input was recorded to test a further pharmacological approach, scavenging CGRP with a CGRP-binding L-RNA oligonucleotide, the L-aptamer NOX-C89. Cumulative ascending doses of NOX-C89 were intravenously infused. RESULTS: Spontaneous activity of spinal trigeminal neurons did not change after 0.05 mg/kg NOX-C89, however, after additional infusion of 0.5 mg/kg and 5 mg/kg NOX-C89, spontaneous activity was dose-dependently reduced. Identical doses of a control L-aptamer had no effect. This pharmacological effect of NOX-C89 was observed 10-25 min after infusion, but no difference was detected in the period 0-5 min. For comparison, the previously investigated CGRP receptor antagonist olcegepant had reduced activity within 5 min after infusion. Alongside the reduced spontaneous activity, after infusion of NOX-C89 the heat-induced neuronal activity was abolished. CONCLUSIONS: Scavenging CGRP by mirror-image RNA aptamers provides further evidence that this approach can be used to control spinal trigeminal activity. [less ▲]

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See detailRaman spectroscopy: comparing the “fingerprints” of C6 glioma and mesenchymal stem cells
Kulchitsky, V.A.; Arzumanyan, G.M.; Dosina, M.O. et al

in Journal of Stem Cells and Regenerative Therapy (2016), 1(1),

Using Coherent anti-Stokes Raman scattering (CARS) mapping we compared the Raman spectra of rat’s C6 glioma cells with those of mesenchymal stem cells. Raman spectroscopy revealed a striking similarity of ... [more ▼]

Using Coherent anti-Stokes Raman scattering (CARS) mapping we compared the Raman spectra of rat’s C6 glioma cells with those of mesenchymal stem cells. Raman spectroscopy revealed a striking similarity of scattering spectra from rat’s mesenchymal stem cells and C6 glioma cells. Our results indicate possible relations between the Mesenchymal Stem Cells (MSCs) and C6 glioma cells, which is in accordance with the studies reporting expression of common antigens in stem cells and various types of tumor [less ▲]

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See detailEffect of electrode morphology on the frquency spectrum of local field potentials in the rat ventral tegmental area
Delairesse, Charlotte ULiege; Seutin, Vincent ULiege; Koulchitsky, Stanislav ULiege

Poster (2016, November 14)

Implantable microelectrode arrays for chronic neural recordings receive an attention by a number of research groups investigating ensemble spike activity and local field potentials. Due to that interest ... [more ▼]

Implantable microelectrode arrays for chronic neural recordings receive an attention by a number of research groups investigating ensemble spike activity and local field potentials. Due to that interest, various types of arrays have been developed. In the present study we compared the LFP signals recorded from the ventral tegmental area (VTA) of freely moving male Wistar rats using the two types of arrays: microelectrode microwire arrays, and silicon-based planar probes. Our choice was based on the difference in the geometry of these two array types. The microwire electrodes have a three-dimensional recording surface around their tips. This allows them to receive the signal from the diverse brain regions. In contrast, the electrode contacts of the planar probe are patterned on one side of the silicon shaft (often named top-side, in contrast to the other, back-side). This configuration mainly allows registering the signal from the top-side of the shaft, while the signal from the back-side gets attenuated. Microwire arrays used in this study consisted of 8 sharpened platinum iridium wires, coated with parylene-C, except for the tip allowing the recording (Alpha Omega GmbH, Israel). Planar probes (ATLAS Neuroengineering, Belgium) had 16 iridium oxide electrode contacts implemented in the 4 silicon shafts, 4 electrode contacts per shaft. The recording was performed using a wireless system (W-Basic-System, Multi Channel Systems MCS GmbH, Germany). The probes were implanted in two orientations: top-side facing the midline, and top-side facing the lateral plane of the brain. For verification of the recording area the rats were anaesthetized and perfused with 4% paraformaldehyde containing 1 % of Gadovist. The brains were removed from the skull and placed in Fomblin for MRI scanning (9.4 Tesla MRI DirectDrive VNMRS, Agilent Technologies, Palo Alto, CA). Frequency spectra of LFP recorded by the microwire arrays, and by the planar probes oriented to the lateral plane of the brain contained a prominent peak in the theta range (6-8 Hz). In contrast, the signal registered using the planar probes oriented to the midline lacked such a peak and was more heterogeneous. We attribute the observed difference to the geometry of the recording platforms. [less ▲]

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See detailOn the management of neurotransmitter imbalance after the use of neurotransmitter ligands or dielectrics in hypoxia
Koulchitsky, Stanislav ULiege; Pashkevich, Svetlana; Grinchik, Nikolay et al

in Proceedings of the seventh Workshop on Experimental Models and Methods in Biomedical Research (2016)

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See detailThe model of endotoxemia in rats after subdiaphragmatic vagotomy
Koulchitsky, Stanislav ULiege; Netukova, Nina; Navratil, Leos et al

in Proceedings of the seventh Workshop on Experimental Models and Methods in Biomedical Research (2016)

Escherichia coli lipopolysaccharide (3 µg/kg) injection intravenously to rats (n=23) is accompanied with development of polyphasic fever and shift of nociceptive reactions threshold to hypo- or ... [more ▼]

Escherichia coli lipopolysaccharide (3 µg/kg) injection intravenously to rats (n=23) is accompanied with development of polyphasic fever and shift of nociceptive reactions threshold to hypo- or hyperalgesia according to fever phase. The blockade of afferent and efferent signals after vagotomy disturbs formation of fever and nociceptive reactions pattern. Therefore, obtained data allow explaining the phenomenon of nociceptive reactions and fever threshold shift after imperative change of signals flow through vagus nerve (for example, during qigong practicing) [less ▲]

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See detailTargeted migration of stem cells in the model of brain trauma
Stukach, Y.; Koulchitsky, Stanislav ULiege; Shanko, Y. et al

in Proceedings of the seventh Workshop on Experimental Models and Methods in Biomedical Research (2016)

Objective: to develop technique of stem cells migration to the brain along trunks of cranial nerves during brain injury modeling. Methods: 40 anesthetized white rats were fixed in stereotaxis and ... [more ▼]

Objective: to develop technique of stem cells migration to the brain along trunks of cranial nerves during brain injury modeling. Methods: 40 anesthetized white rats were fixed in stereotaxis and subjected to craniotomy (20 rats at anterior cranial fossa (group 1) and 20 rats at posterior cranial fossa (group 2). 100 µl of brain tissue were bilaterally aspirated from somatosensory zone and cerebellar cortex in 1st and 2nd groups, respectively. Mesenchymal stem cells (labeled with PKH67 green fluorescent linker) were injected in 10 minutes: intranasally (10 animals) and to Meckel cavity (10 animals) in both groups. Animals were observed and sacrificed at certain periods of time after the operation during three weeks. Results: Appearance of small groups of mesenchymal stem cells in cranial cavity was established in 30 minutes after the operation. The highest fluorescence was observed at the damaged zone from 14 till 21 day after labeled stem cells implantation. Mesenchymal stem cells were predominantly distributed at the damaged zone in anterior cranial fossa after intranasal injection, and injection of stem cells to Meckel cavity resulted in their pronounced accumulation in the zone of cerebellar cortex injury (posterior cranial fossa). Conclusion: The fact of somatotopic arrangement of mesenchymal stem cells in cranial cavity according to application zone near cranial nerve endings was established. Intranasal injection of mesenchymal stem cells is followed by their distribution in damaged zone in anterior cranial fossa. Injection of mesenchymal stem cells to Meckel cavity leads to accumulation of labeled cells in damaged zone in posterior cranial fossa. [less ▲]

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See detailBehavior in the open field predicts the number of KCl-induced cortical spreading depressions in rats.
Bogdanov, Volodymyr Borysovych; Bogdanova, Olena Viktorivna; Koulchitsky, Stanislav ULiege et al

in Behavioural Brain Research (2013), 236(1), 90-3

Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility ... [more ▼]

Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility to CSD and anxiety we used the open field test in male Sprague-Dawley rats chronically treated with the preventive anti-migraine drugs valproate or riboflavin. Animals avoiding the central area of the open field chamber and those with less exploratory activity (i.e. rearing) were considered more anxious. After 4 weeks of treatment CSDs were elicited by application of 1M KCl over the occipital cortex and the number of CSDs occurring over a 2h period was compared to the previously assessed open field behavior. Higher anxiety-like behavior was significantly correlated with a higher frequency of KCl-induced CSDs. In saline-treated animals, fewer rearings were found in animals with more frequent CSDs (R=-1.00). The duration of ambulatory episodes in the open field center correlated negatively with number of CSDs in the valproate group (R=-0.83; p<0.005) and in riboflavin treated group (R=-0.69; p<0.05) as well as total time spent in the open field center in both groups (R=-0.75; p<0.05 and R=-0.58; p<0.1 respectively). These results suggest that anxiety symptoms are associated with susceptibility to CSD and might explain why it can be an aggravating factor in migraine with aura. [less ▲]

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See detailDifferential Effects of Cocaine on Dopamine Neuron Firing in Awake and Anesthetized Rats
Koulchitsky, Stanislav ULiege; DE BACKER, Benjamin ULiege; Quertemont, Etienne ULiege et al

in Neuropsychopharmacology (2012), 37

Cocaine (benzoylmethylecgonine), a natural alkaloid, is a powerful psychostimulant and a highly addictive drug. Unfortunately, the relationships between its behavioral and electrophysiological effects are ... [more ▼]

Cocaine (benzoylmethylecgonine), a natural alkaloid, is a powerful psychostimulant and a highly addictive drug. Unfortunately, the relationships between its behavioral and electrophysiological effects are not clear. We investigated the effects of cocaine on the firing of midbrain dopaminergic (DA) neurons, both in anesthetized and awake rats, using pre-implanted multielectrode arrays and a recently developed telemetric recording system. In anesthetized animals, cocaine (10 mg/kg, intraperitoneally) produced a general decrease of the firing rate and bursting of DA neurons, sometimes preceded by a transient increase in both parameters, as previously reported by others. In awake rats, however, injection of cocaine led to a very different pattern of changes in firing. A decrease in firing rate and bursting was observed in only 14% of DA neurons. Most of the other DA neurons underwent increases in firing rate and bursting: these changes were correlated with locomotor activity in 52% of the neurons, but were uncorrelated in 29% of them. Drug concentration measurements indicated that the observed differences between the two conditions did not have a pharmacokinetic origin. Taken together, our results demonstrate that cocaine injection differentially affects the electrical activity of DA neurons in awake and anesthetized states. The observed increases in neuronal activity may in part reflect the cocaine-induced synaptic potentiation found ex vivo in these neurons. Our observations also show that electrophysiological recordings in awake animals can uncover drug effects, which are masked by general anesthesia. [less ▲]

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See detailChanges in Neuropil Ultrastructure in Hippocampal Field CA1 in Rat Pups after Application of Hyaluronidase
Koulchitsky, Stanislav ULiege; Yakubovich, N.V.; Emel’yanova, A.A. et al

in Neuroscience and Behavioral Physiology (2009), 39(6), 517-521

Electron microscopy and electrophysiological studies were performed on cross-sectional slices of the hippocampus of four-week-old male rat pups (n = 35) to detect ultrastructural changes in hippocampal ... [more ▼]

Electron microscopy and electrophysiological studies were performed on cross-sectional slices of the hippocampus of four-week-old male rat pups (n = 35) to detect ultrastructural changes in hippocampal field CA1 and the characteristics of the formation of excitatory postsynaptic potentials in this area of the brain after incubation of slices in hyaluronidase solution (10 U/ml), whose specific substrate is the extracellular matrix glycosaminoglycan hyaluronic acid. At 1.5 min after enzyme application, there were reductions in synaptic cleft widths in axodendritic contacts of the striatum radiatum of hippocampal field CA1 by 15–25%, which were consistent with increases seen in the amplitudes of excitatory postsynaptic potentials. At 4.5 min of incubation, the lumens of synaptic clefts decreased by 45–55%: during this time there was blockade of signal transmission via Schäffer collaterals to hippocampal field CA1. Thus, the structural-functional state of glycosaminoglycans is among the factors determining the efficiency of synaptic transmission in the brain. [less ▲]

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See detailCalcitonin gene-related peptide receptor inhibition reduces neuronal activity induced by prolonged increase in nitric oxide in the rat spinal trigeminal nucleus
Koulchitsky, Stanislav ULiege; Fischer, M. J. M.; Messlinger, K.

in Cephalalgia (2009), 29(4), 408--417

Infusion of nitric oxide (NO) donors is known to induce delayed attacks of migraine and cluster headache or aggravate tension-type headaches in patients suffering from these primary headaches. Previously ... [more ▼]

Infusion of nitric oxide (NO) donors is known to induce delayed attacks of migraine and cluster headache or aggravate tension-type headaches in patients suffering from these primary headaches. Previously we have reported that infusion of NO donors in the rat causes delayed neuronal activity in the spinal trigeminal nucleus, which parallels the above clinical observations. Suggesting that endogenous NO production is involved in the generation of primary headaches, we used this animal model of meningeal nociception to determine whether a prolonged increase in NO levels causes an increase in neuronal activity. In anaesthetized rats spinal trigeminal neurons with afferent input from the exposed dura were recorded. Continuous intravenous infusion of the NO donors sodium nitroprusside (25 mg/kg/h) or glycerol trinitrate (250 mg/ kg/h) for 2 h induced a persisting increase in neuronal activity but no change in systemic blood pressure. In this activated trigeminal system the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS (900 mg/ kg) was infused. Spinal trigeminal activity was significantly reduced within minutes and to a similar extent as previously reported in animals not treated with NO. Slow continuous NO infusion may be a model of the active headache phase, and inhibition of CGRP receptors can reverse the induced neuronal activity. [less ▲]

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See detailRelease of calcitonin gene-related peptide from the jugular--nodose ganglion complex in rats--A new model to examine the role of cardiac peptidergic and nitrergic innervation
Strecker, Thomas; Koulchitsky, Stanislav ULiege; Dieterle, Anne et al

in Neuropeptides (2008), 42(5), 543--550

Objective: Afferent information from the heart and the lung is conveyed to the brainstem by primary afferent fibers originating from vagal sensory neurons (jugular–nodose ganglion complex, JNC). The ... [more ▼]

Objective: Afferent information from the heart and the lung is conveyed to the brainstem by primary afferent fibers originating from vagal sensory neurons (jugular–nodose ganglion complex, JNC). The present study was made to evaluate if release of the sensory neuropeptide calcitonin gene-related peptide (CGRP) from the JNC can be used as a model for future studies on changes in neuropeptide release under pathological conditions of the heart. Methods: Freshly isolated rat JNC’s were passed through a series of solutions based on oxygenated synthetic interstitial fluid (SIF). Substances such as the TRPV1 receptor agonist capsaicin and the nitric oxide (NO) donor sodium nitroprusside (SNP) were added as excitatory test stimuli. The eluates were processed using an enzyme immuno-assay (EIA) for measurement of CGRP concentrations. Immunohistochemistry was used to visualize CGRP containing and NO producing neurons in the JNC. Results: Both SNP and capsaicin caused significant increases in CGRP release. CGRP-immunoreactive neurons (somata) were preferentially found in the jugular ganglion, whereas neurons immunoreactive for neuronal NO synthase were mostly localized in the nodose ganglion. Conclusion: The present study demonstrates an easily reproducible model for measuring stimulated CGRP release from vagal afferents arising from the JNC. Nitric oxide produced by vagal afferents may stimulate CGRP release upon afferent activation. [less ▲]

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See detailActions of Nociceptive Mediators in the Trigeminovascular System as a Basis for the Generation of Headaches
Messlinger, K.; De Col, R.; Denekas, T. et al

in Aktuelle Neurologie (2007), 34(9), 504--507

Nociceptive mechanisms in the trigeminovascular system are probably involved in the generation of different forms of hedaches, wherein the neuropeptide CGRP (calcitonin gene-related peptide), which is ... [more ▼]

Nociceptive mechanisms in the trigeminovascular system are probably involved in the generation of different forms of hedaches, wherein the neuropeptide CGRP (calcitonin gene-related peptide), which is released from a subset of activated primary afferents, is regarded as an important mediator. CGRP is not only a potent vasodilator but is also involved in nociceptive transmission in the trigeminal nucleus. Inhibition of CGRP receptors by the high-affinity CGRP receptor antagonist BIBN4096BS, which had proved its therapeutic potency in migraine patients, led to a significant decrease in neuronal activity in the spinal trigeminal nucleus of the rat. Another important vasodilatory mediator in meningeal nociception seems to be nitric oxide (NO), which may facilitate CGRP release from peripheral and central trigeminal structures. Inhibition of NO generation was effective in lowering the neuronal activity in the spinal trigeminal nucleus as well, whereas infusion of NO donors led to an increase in activity. The activiation showed typically a biphasic pattern. The delayed response can only be explained by secondary processes such as the expression of pro-nociceptive substances in the trigeminal nucleus or ganglion, as indicated by preliminary experimental studies. The fact that clinical and basic experimental data complement each other highlights the interpretative value of basic experiments for the pathophysiological mechanisms underlying the generation of headaches. [less ▲]

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See detailOngoing activity in trigeminal wide-dynamic range neurons is driven from the periphery
Roch, Michael; Messlinger, K.; Kulchitsky, V. et al

in Neuroscience (2007), 150(3), 681--691

Ongoing activity of spinal trigeminal neurons is observed under various conditions and suggested to be responsible for ongoing headache. It can be spontaneous, i.e. arising intrinsically from the neuron ... [more ▼]

Ongoing activity of spinal trigeminal neurons is observed under various conditions and suggested to be responsible for ongoing headache. It can be spontaneous, i.e. arising intrinsically from the neuron, or the product of descending influences from other central neurons, or maintained by ongoing afferent input. The aim of the present study was to examine if ongoing activity of neurons in different subnuclei of the spinal trigeminal nucleus is driven from peripheral afferent input. Experiments were performed in Wistar rats anesthetized with isoflurane or Nembutal/urethane. Ongoing activity of single wide-dynamic range (WDR) neurons was recorded with carbon fiber glass microelectrodes in two subnuclei of the spinal trigeminal nucleus: oral (Sp5O) and caudal (Sp5C). Peripheral receptive fields were evaluated using von Frey filaments. Sp5O neurons received peripheral input from facial areas innervated by the mandibular branch of the trigeminal nerve. Units in Sp5C had receptive fields in the surgically exposed dura mater and in facial areas innervated by the ophthalmic and maxillary branch of the trigeminal nerve. Saline or the local anesthetic lidocaine was locally applied onto the exposed dura mater or microinjected into V3 (for Sp5O units) or V1/V2 (for Sp5C units) divisions of the trigeminal ganglion via the infraorbital channel. Local application of lidocaine onto the exposed dura caused mechanical insensitivity of dural receptive fields but not significant decrease in ongoing activity. Microinjection of lidocaine but not saline into the trigeminal ganglion was followed by a substantial decrease in both the receptive field size and the activity of the recorded WDR units. Mechanical insensitivity of receptive fields after trigeminal ganglion blockade was accompanied by the disappearance of ongoing activity. We conclude that the ongoing activity of WDR neurons in the spinal trigeminal nucleus, which may be indicative for processes of sensitization, is driven remotely by ongoing afferent input. [less ▲]

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See detailThe nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS lowers the activity of neurons with meningeal input in the rat spinal trigeminal nucleus
Fischer, Michael Jochen Marco; Koulchitsky, Stanislav ULiege; Messlinger, Karl

in Journal of Neuroscience (2005), 25(25), 5877--5883

Calcitonin gene-related peptide (CGRP) has been suggested to play a major role in the pathogenesis of migraines and other primary headaches. CGRP may be involved in the control of neuronal activity in the ... [more ▼]

Calcitonin gene-related peptide (CGRP) has been suggested to play a major role in the pathogenesis of migraines and other primary headaches. CGRP may be involved in the control of neuronal activity in the spinal trigeminal nucleus (STN), which integrates nociceptive afferent inputs from trigeminal tissues, including intracranial afferents. The activity of STN neurons is thought to reflect the activity of central trigeminal nociceptive pathways causing facial pain and headaches in humans. In a rat model of meningeal nociception, single neuronal activity in the STN was recorded. All units had receptive fields located in the exposed parietal dura mater. Heat and cold stimuli were repetitively applied to the dura in a fixed pattern of ramps and steps. The nonpeptide CGRP receptor antagonist BIBN4096BS was topically applied onto the exposed dura or infused intravenously. BIBN4096BS (300 microg/kg, i.v.) reduced spontaneous activity by approximately 30%, the additional dose of 900 microg/kg intravenously by approximately 50% of the initial activity, whereas saline had no effect. The activity evoked by heat ramps was also reduced after BIBN4096BS (900 microg/kg, i.v.) by approximately 50%. Topical administration of BIBN4096BS (1 mm) did not significantly change the spontaneous neuronal activity within 15 min. We conclude that the endogenous release of CGRP significantly contributes to the maintenance of spontaneous activity in STN neurons. Blockade of CGRP receptors, possibly at central and peripheral sites, may therefore be an effective way to decrease nociceptive transmission. This may offer a new therapeutic strategy for the treatment of facial pain and primary headaches [less ▲]

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See detailBiphasic response to nitric oxide of spinal trigeminal neurons with meningeal input in rat--possible implications for the pathophysiology of headaches
Koulchitsky, Stanislav ULiege; Fischer, M. J.; De Col, Roberto et al

in Journal of Neurophysiology (2004), 92(3), 1320-8

Nitric oxide (NO) is suggested to play a causative role in the pathogenesis of primary headaches. Infusion of NO donors can trigger headache attacks, and products of NO metabolism are found to be ... [more ▼]

Nitric oxide (NO) is suggested to play a causative role in the pathogenesis of primary headaches. Infusion of NO donors can trigger headache attacks, and products of NO metabolism are found to be increased in the cranial circulation in patients suffering from such headaches. To examine if NO is involved in mediating and maintaining spinal trigeminal neuronal activity, an animal model of meningeal nociception was used. In barbiturate-anesthetized rats, a cranial window was made to expose the parietal dura mater. An access to the medullary brain stem allowed extracellular action potentials to be recorded from neurons in the spinal trigeminal nucleus that received afferent input from the exposed dura. Slow intravenous infusion of the NO donor, sodium nitroprusside (SNP, 50 microg/kg), transiently increased spontaneous activity in a subset of neurons and, with a latency of 50 min, caused a progressive increase in impulse activity across the entire sample of neurons. A similar pattern of delayed activation was seen after topical application of the same dose of SNP onto the exposed medulla. Slow injection of the nonspecific inhibitor of NO synthase, N(omega)-nitro-l-arginine methyl ester (20 mg/kg), reduced the spontaneous activity in all neurons within 15 min. The results suggest that NO can induce delayed, slowly developing activation of central trigeminal neurons and that endogenous release of NO may contribute to the ongoing activity of these neurons. The delayed changes in neuronal activity may include gene expression of pro-nociceptive mediators. These mechanisms may be relevant for the pathogenesis of chronic headaches. [less ▲]

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See detailCorrelation between Paired Responses Confirms the Existence of a Positive Ephaptic Feedback in Central Synapses
Koulchitsky, Stanislav ULiege; (Kulchitsky); Maximov, V. V. et al

in Doklady Biological Sciences (2003), 389(1), 102-104

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See detailNitric oxide synthase inhibition lowers activity of neurons with meningeal input in the rat spinal trigeminal nucleus
De Col, R.; Koulchitsky, Stanislav ULiege; Messlinger, K. B.

in Neuroreport (2003), 14(2), 229-32

Nitric oxide is thought to control transmitter release and neuronal activity in the spinal dorsal horn and the spinal trigeminal nucleus, where nociceptive information from extra- and intracranial tissues ... [more ▼]

Nitric oxide is thought to control transmitter release and neuronal activity in the spinal dorsal horn and the spinal trigeminal nucleus, where nociceptive information from extra- and intracranial tissues is processed. Extracellular impulse activity was recorded from neurons in the rat spinal trigeminal nucleus with afferent input from the cranial dura mater. In contrast to the inactive isomer D-NAME, infusion of the nitric oxide synthase inhibitor L-NAME (20 mg/kg) significantly reduced neuronal activity and increased systemic blood pressure. It is concluded that nitric oxide production contributes to the ongoing activity of sensitized neurons in the spinal trigeminal nucleus. The results suggest that nitric oxide may be involved in the generation and maintenance of primary headaches such as migraine. [less ▲]

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