Biomedical subjects

G Jancsó

Publications and source records attributed to G Jancsó.

At least 19 recordsLinked to original sources

PubMed2004

Analyzing of segregation in mixtures of 3-methylpyridine and heavy water by dynamic neutron radiography.

The closed-loop phase diagram of 3-methylpyridine-heavy water mixture was studied, to our best knowledge, for the first time with dynamic neutron radiography (DNR) at the 10MW VVR-SM Research Reactor in Budapest (Hungary). Visualized were the (i) lower temperature non-segregated states (below 38 degrees C), (ii) transition (40-43 degrees C), (iii) segregated states (46-128 degrees C), (iv) higher temperature transition (110-128 degrees C) and (v) higher temperature non-segregated states. The non-segregated state belonging to 141 degrees C, was found to be definitely dissimilar from the lower temperature state. Existence of a solid-like structure at the liquid-liquid interface was indicated.

Journal Article↗

PubMed2004

Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries.

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1-TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea.

Animals↗

PubMed2003

Transganglionic transport of choleragenoid by capsaicin-sensitive C-fibre afferents to the substantia gelatinosa of the spinal dorsal horn after peripheral nerve section.

Choleratoxin B subunit-binding thick myelinated, A-fibre and unmyelinated, capsaicin-sensitive nociceptive C-fibre primary afferent fibres terminate in a strict topographic and somatotopic manner in the spinal cord dorsal horn. Injection of choleratoxin B subunit-horseradish peroxidase conjugate into injured but not intact peripheral nerves produced transganglionic labelling of primary afferents not only in the deeper layers (Rexed's laminae III-IV), but also in the substantia gelatinosa (Rexed's laminae II) of the spinal dorsal horn. This was interpreted in terms of a sprouting response of the Abeta-myelinated afferents and suggested a contribution to the pathogenesis of neuropathic pain [Nature 355 (1992) 75; J Comp Neurol 360 (1995) 121]. By utilising the selective neurotoxic effect of capsaicin, we examined the role of C-fibre sensory ganglion neurons in the mechanism of this phenomenon. Elimination of these particular, capsaicin-sensitive C-fibre afferents by prior intrathecal or systemic capsaicin treatment inhibited transganglionic labelling by the choleratoxin B subunit-horseradish peroxidase conjugate of the substantia gelatinosa evoked by chronic sciatic nerve section. More importantly, prior perineural capsaicin treatment of the transected nerve proximal to the anticipated site of injection of choleragenoid 12 hours later prevented the labelling of the substantia gelatinosa, but not that of the deeper layers. Electron microscopic examination of the dorsal roots revealed no significant difference in the proportion of labelled myelinated fibres relating to the intact (54.4+/-5.5%) and the transected (62.4+/-5.4%) sciatic nerves. In contrast, the proportion of labelled unmyelinated dorsal root axons relating to the transected, but not the intact nerves showed a significant, six-fold increase after sciatic nerve transection (intact: 4.9+/-1.3%; transected: 35+/-6.7%). These observations indicate that peripheral nerve lesion-induced transganglionic labelling of the substantia gelatinosa by choleratoxin B subunit-horseradish peroxidase may be primarily accounted for by the uptake and transganglionic transport of choleragenoid by injured capsaicin-sensitive C-fibre afferents rather than a sprouting response of A-fibre afferents. The present findings suggest an essential role of capsaicin-sensitive primary sensory neurons in lesion-induced spinal neuroplastic changes and provide further support for C-fibre nociceptor neurons being promising targets for the development of new strategies in pain management.

Afferent Pathways↗

PubMed2002

Peripheral nerve lesion-induced uptake and transport of choleragenoid by capsaicin-sensitive c-fibre spinal ganglion neurons.

In the present experiments the effect of systemic capsaicin treatment on the retrograde labelling of sensory ganglion cells was studied following the injection of choleratoxin B subunit-horseradish peroxidase conjugate (CTX-HRP) into intact and chronically transected peripheral nerves. In the control rats CTX-HRP injected into intact sciatic nerves labelled medium and large neurons with a mean cross-sectional area of 1,041 +/- 39 gm2. However, after injection of the conjugate into chronically transected sciatic nerves of the control rats, many small cells were also labelled, shifting the mean cross-sectional area of the labelled cells to 632 +/- 118 microm2. Capsaicin pretreatment per se induced a moderate but significant decrease in the mean cross-sectional area of the labelled neurons (879 +/- 79 microm2). More importantly, systemic pretreatment with capsaicin prevented the peripheral nerve lesion-induced labelling of small cells. Thus, the mean cross-sectional areas of labelled neurons relating to the intact and transected sciatic nerves, respectively, did not differ significantly. These findings provide direct evidence for a phenotypic switch of capsaicin-sensitive nociceptive neurons after peripheral nerve injury, and suggest that lesion-induced morphological changes in the spinal cord may be related to specific alterations in the chemistry of C-fibre afferent neurons rather than to a sprouting response of A-fibre afferents.

Animals↗

PubMed2001

Capsaicin stimulation of the cochlea and electric stimulation of the trigeminal ganglion mediate vascular permeability in cochlear and vertebro-basilar arteries: a potential cause of inner ear dysfunction in headache.

Trigeminal neurogenic inflammation is one explanation for the development of vascular migraine. The triggers for this inflammation and pain are not well understood, but are probably vasoactive components acting on the blood vessel wall. Migraine-related inner ear symptoms like phonophobia, tinnitus, fluctuation in hearing perception and increased noise sensitivity provide indirect evidence that cochlear blood vessels are also affected by basilar artery migraine. The purpose of this investigation was to determine if a functional connection exists between the cochlea and the basilar artery. Neuronally mediated permeability changes in the cochlea and basilar artery were measured by colloidal silver and Evans Blue extravasation, following orthodromic and antidromic stimulation of the trigeminal ganglion innervating the cochlea. Capsaicin and electrical stimulation induced both dose- and time-dependent plasma extravasation of colloidal silver and Evans Blue from the basilar artery and anterior inferior cerebellar artery. Both orthodromic and antidromic activation of trigeminal sensory fibers also induced cochlear vascular permeability changes and significant quantitative differences between the treated and control groups in spectrophotometric assays. These results characterize a vasoactive connection between the cochlea and vertebro-basilar system through the trigeminal sensory neurons. We propose that vertigo, tinnitus and hearing deficits associated with basilar migraine could arise by excitation of the trigeminal nerve fibers in the cochlea, resulting in local plasma extravasation. In addition, cochlear "dysfunction" may also trigger basilar and cluster headache by afferent input to the trigeminal system.

Animals↗

PubMed2000

Inhibitory neurogenic modulation of histamine-induced cutaneous plasma extravasation in the pigeon.

The neurohumoral modulation of the permeability increasing effect of histamine was studied in pigeon skin. Substances were administered through plasmapheresis capillaries inserted into the dorsal wing skin and the protein contents of the perfusates were determined by a quantitative method. The vascular labelling technique was also utilized to histologically identify leaky blood vessels. In the innervated skin histamine evoked a significant, dose-dependent plasma extravasation which was markedly augmented by the coadministration of a specific galanin receptor antagonist, galanin-1-16-bradykinin-2-9-amide (M35). Chronic cutaneous denervation per se resulted in a significant elevation of the permeability-enhancing effect of histamine. In the denervated skin this response was not affected by M35 but was significantly inhibited by galanin. It is concluded that in the normally innervated skin endogenous galanin may exert a neurogenic tonic inhibitory effect on histamine-induced plasma leakage. It is suggested that sensory nerves possess not only pro-inflammatory, but also anti-inflammatory (inhibitory) sensory-efferent functions.

Animals↗

PubMed2000

Capsaicin-sensitive mechanisms are involved in cortical spreading depression-associated cerebral blood flow changes in rats.

We tested the hypothesis that capsaicin-sensitive mechanisms play a role in the cortical spreading depression (CSD)-related changes in cortical blood flow (CBF). CBF was measured with laser Doppler flowmetry in anesthetized rats. The animals were treated with capsaicin before (48 h-2 weeks) or during the experiments. This agent is thought to stimulate small-diameter sensory nerve fibers selectively and to deplete stored peptides. In the vehicle-treated group (n=8), the peak value of the CSD-associated hyperperfusion was 257+/-12% above the baseline (mean+/-SEM, P<0.05). In the groups treated with 20 and 40 microg/kg or 20 mg/kg capsaicin, there were only small decreases in CBF. In the groups treated with 100 mg/kg capsaicin, the CSD-associated hyperemia was reduced at 48 h (158+/-7%, P<0.05). However, at 96 h a transient hyperresponsiveness (390+/-38%, P<0.05) was observed, which had disappeared by 2 weeks. These results indicate that the manipulation of sensory neuropeptide stores results in a biphasic effect on CSD-induced CBF responses.

Animals↗

PubMed1999

Inhibitory modulation of cutaneous vascular responses by endogenous galanin in the pigeon.

The possible role of endogenous galanin in modulation of cutaneous vascular responses was studied in pigeons. Chemically induced plasma extravasation and regional skin blood flow changes were measured simultaneously with a capillary perfusion technique and a laser Doppler imager, respectively. Perfusion with both histamine and bradykinin increased plasma protein extravasation which was dose-dependently and significantly augmented by co-administration of M35, a specific galanin antagonist. This effect of M35 was abolished after chronic cutaneous denervation. In intact but not denervated skin, M35 increased the vasodilatatory effect of histamine, too. It is suggested that galanin-containing nerves may play an inhibitory efferent role in the modulation of cutaneous inflammatory responses.

Animals↗

PubMed1999

Changes in fibre populations of the rat hairy skin following selective chemodenervation by capsaicin.

Perineural application of capsaicin results in a selective and permanent reduction in the sensitivity to noxious chemical and heat stimuli and elimination of the neurogenic inflammatory response. The present quantitative immunohistochemical study has been undertaken to reveal the populations of cutaneous afferent nerves that are affected by perineural capsaicin treatment. Areas of intact and chemodenervated skin were determined with the aid of the vascular labelling technique. In sections taken from intact skin areas, staining with antibodies against protein gene product 9.5 revealed a rich epidermal innervation. Fibres immunoreactive for growth-associated protein 43 were also abundant; nerve fibres immunoreactive for substance P and calcitonin gene-related peptide were less numerous. Somatostatin- and RT97-immunoreactive fibres were seen only in the subepidermal layer. In sections taken from skin areas supplied by the sciatic nerve treated with capsaicin 3 days previously, the number of epidermal nerve fibres immunoreactive to protein gene product 9.5, growth-associated protein 43, substance P and calcitonin gene-related peptide was reduced by 90%, 95%, 97% and 66%, respectively. These changes persisted for at least 42 days. The findings reveal that the majority of epidermal axons are capsaicin-sensitive and comprise a chemically heterogeneous population. Reductions in cutaneous fibre populations following perineural capsaicin treatment may result from both the degeneration of sensory axons and the depletion of neuron-specific macromolecules. In addition, most cutaneous nociceptive axons may not use the major sensory neuropeptides substance P and calcitonin gene-related peptide as afferent neurotransmitters.

Animals↗

PubMed1999

Galanin mediated inhibitory nervous modulation of cutaneous vascular reactions.

Noxious stimulation induces local inflammatory responses in a variety of mammals but these reactions are only faint in avian species. The possibility that endogenous galanin inhibits neurogenic vascular responses in avians was tested in the wing skin of anaesthetized pigeons. Intraarterial infusion of nanomolar concentrations of the specific galanin antagonist M35 dose dependently enhanced the small mustard oil induced increase of skin blood flow measured by means of a Laser Doppler Imager. Similarly, the small transient vasodilatation following electrical stimulation of a cutaneous nerve was also enhanced by M35. The effect of M35 was not observed after chronic denervation. Coperfusion of M35 dose dependently augmented the histamine and bradykinin induced plasma extravasation revealed by skin microdialyses, but this effect was abolished in the chronically denervated skin. However, chronic denervation per se enhanced the plasma extravasation induced by histamine but not by bradykinin and this effect was diminished by coperfusion of galanin. The results suggest an inhibitory modulation of cutaneous neurogenic inflammatory reactions by endogenous galanin in the pigeon.

Animals↗

PubMed1998

Beta-amyloid (1-42) peptide impairs blood-brain barrier function after intracarotid infusion in rats.

The effects of intracarotid infusions of beta-amyloid (1-42) peptide was studied on the permeability of brain vessels. Using a quantitative Evans blue method a dose-dependent increase of brain tissue albumin content was established following intracarotid injections of the peptide. Cerebral vessels of increased permeability were also demonstrated with a vital 'staining' technique. Lectin histochemistry revealed an almost complete abolition of specific lectin binding sites of affected endothelial cells. The findings indicate a significant deterioration by beta-amyloid (1-42) peptide of blood-brain barrier function and suggest that this may result from endothelial damage. It is assumed that altered permeability of cerebral vessels may be involved in the development of brain pathologies associated with Alzheimer's disease.

Amyloid beta-Peptides↗

PubMed1998

Evidence for an inhibition by endogenous galanin of neurogenic cutaneous vasodilatation in the pigeon.

The effect of high affinity galanin antagonist M35 on neurogenic cutaneous vasodilatation has been studied in the pigeon using a Laser Doppler Imager. Cutaneous application of mustard oil or antidromic electrical stimulation of a cutaneous nerve produced a small increase in skin blood flow. Close arterial injection of M35 prior to chemical or electrical stimulation resulted in a marked augmentation of the vasodilatory response. This effect was abolished by chronic denervation. The results suggest a nerve-mediated inhibitory effect of endogenous galanin on neurogenic cutaneous vasodilatation in the pigeon skin and provide the first experimental evidence for an inhibitory local regulatory function of cutaneous sensory nerves at least in the avian skin.

Animals↗

PubMed1997

Capsaicin-sensitive local sensory innervation is involved in pacing-induced preconditioning in rat hearts: role of nitric oxide and CGRP?

UNLABELLED: Among several mediators, nitric oxide (NO) and calcitonin gene-related peptide (CGRP) were suggested to be involved in the mechanism of preconditioning. We examined the possible role of the cardiac capsaicin-sensitive sensory innervation in pacing-induced preconditioning, as well as in the cardiac NO and CGRP content. Wistar rats were treated subcutaneously with capsaicin or its solvent in the sequence of 10, 30, and 50 mg/kg increasing single daily doses for 3 days to deplete neurotransmitters of the sensory innervation. Isolated hearts from both groups were then subjected to either preconditioning induced by three consecutive periods of pacing at 600 beats per minute for 5 min with 5 min interpacing periods, or time-matched non-preconditioning perfusion, followed by a 10-min coronary occlusion. NO content of left ventricular tissue samples was assayed by electron-spin resonance, and CGRP release was determined by radioimmunoassay. CGRP immunohistochemistry was also performed. In the non-preconditioned, solvent-treated group, coronary occlusion decreased cardiac output (CO) from 68.1 to 32.1 mL/min, increased left ventricular end-diastolic pressure (LVEDP) from 0.58 to 1.90 kPa, and resulted in 200 mU/min/g LDH release. Preconditioning significantly increased ischaemic CO to 42.9 mL/min (P < 0.05), decreased ischaemic LVEDP to 1.26 kPa (P < 0.05) and decreased LDH release to 47 mU/min/g (P < 0.05) in the solvent-treated group. Preconditioning did not confer protection in the capsaicin-pretreated group (ischaemic CO: 35.6 mL/min; LVEDP: 1.76 kPa; LDH 156 mU/min/g). Capsaicin-treatment markedly decreased cardiac NO content, CGRP release, and CGRP-immunoreactivity. CONCLUSIONS: (i) The presence of an intact local sensory innervation is a prerequisite to elicit pacing-induced preconditioning in the rat heart. (ii) A significant portion of cardiac basal NO content may be of neural origin. (iii) Release of NO and CGRP from capsaicin-sensitive nerves may be involved in the mechanism of pacing-induced preconditioning.

Animals↗

PubMed1997

Trigeminal ganglion innervation of the cochlea--a retrograde transport study.

Innervation patterns of sensory nerves from the trigeminal ganglion to the cochlear blood vessels were studied using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Guinea-pigs (n=7) were unilaterally implanted with an osmotic pump and a cannula for cochlear delivery of 2% or 20% wheat germ agglutinin horseradish peroxidase (Group 1), 2% wheat germ agglutinin-horseradish peroxidase followed by 100 micromol capsaicin (Group 2), or vehicle alone. Histological sections of the trigeminal ganglia, the C1 and C2 dorsal ganglia, the superior and inferior ganglia of the glossopharyngeal nerve bilaterally, the midbrain and the brainstem were obtained after 48 h of infusion. In Group 1, a large number of labeled nerve cell bodies were observed in the anteromedial portion of the trigeminal ganglion and at the origin of the ophthalmic nerve. Some labeled cells were also found on the lateral side of the ophthalmic nerve, as well as on the medial side of the maxillary nerve root. Capsaicin pretreatment significantly reduced the density of labeled neurons in the trigeminal ganglion. A few labeled neurons were also found in the trigeminal brainstem nucleus complex and in certain auditory brainstem nuclei. No wheat germ agglutinin horseradish peroxidase-positive cells were observed in the spinal C1 or C2 cervical ganglia or in the superior or inferior glossopharyngeal ganglia. In contrast, wheat germ agglutinin-horseradish peroxidase application to the middle ear resulted in labeled cells in the middle posterolateral portion of the trigeminal ganglia and in the superior ganglia of the glossopharyngeal nerve. These results provide the first direct evidence that the trigeminal ganglion sends projections to the cochlea.

Animals↗

PubMed1996

Neurogenic inflammation in the gastrointestinal tract of the rat.

In contrast to the skin and some visceral organs the capability of capsaicin-sensitive sensory nerves of evoking an inflammatory response in the gastrointestinal tract is equivocal. We have therefore investigated the neurogenic plasma extravasation induced by local application of capsaicin to the stomach, duodenum, jejunum, ileum and colon of the rat. Permeable vessels were visualised histologically with the vascular labelling technique using colloidal silver. In the smooth muscle layer of the small intestine, capsaicin elicited a 3-fold increase in the density of labelled blood vessels (diameter, 7-35 microns). Significant capsaicin-evoked plasma extravasation was also observed in the submucosa of the jejunum and ileum, and in the basal layer of the jejunal mucosa. Capsaicin-induced extravasation was not noted in the stomach and the colon. The data suggest the involvement of capsaicin-sensitive afferents in inflammatory processes in the rat small intestine.

Animals↗

PubMed1996

Inhibition of the neurogenic inflammatory response by lidocaine in rat skin.

Axon reflex vasodilatation and neurogenic plasma extravasation are characteristic cutaneous vascular responses mediated by neuropeptides released from stimulated capsaicin-sensitive sensory nerve endings. Intracutaneous injections of local anaesthetics inhibit the axon-reflex flare elicited by chemical irritants in human skin. Results of earlier reports on the effects of local anaesthetics on neurogenic plasma extravasation are controversial. The aim of the present study, therefore, was to re-examine the effect of the local anaesthetic lidocaine on the neurogenic inflammatory response of rat skin. The effects of lidocaine on cutaneous inflammatory reactions were measured quantitatively by means of the Evans blue technique. Intracutaneous injection of lidocaine resulted in a dose-dependent inhibition of the neurogenic inflammation elicited by mustard oil and of the dye leakage response to compound 48/80 or histamine. It is suggested that the site of this inhibition is beyond the sensory nerve terminal, presumably at the level of the vascular endothelium.

Anesthetics, Local↗

PubMed1995

Reduction of substance P binding sites in the spinal dorsal horn after perineural capsaicin treatment in the rat.

The long-term effect of perineural capsaicin treatment on the distribution of substance P (SP) binding sites was studied in the rat spinal dorsal horn using 125I-labelled Bolton-Hunter-SP. Three months after local application of capsaicin onto the sciatic nerve quantitative evaluation of the autoradiograms revealed a significant decrease in the density of SP binding sites of up to 48% in regions of laminae I and II of the spinal dorsal horn somatotopically related to the capsaicin treated sciatic nerve. It is suggested that reduction in SP binding may result from transganglionic and transsynaptic degenerative changes affecting postsynaptic structures. Changes in the distribution of SP binding sites may significantly contribute to functional alterations observed after perineural treatment with capsaicin.

Afferent Pathways↗

PubMed1995

In vitro capsaicin-induced cytological changes and alteration in calcium distribution in giant serotonergic neurons of the snail Helix pomatia: a light- and electron-microscopic study.

Morphological changes induced by capsaicin were studied in the serotonergic metacerebral giant neurons of the cerebral ganglia of Helix pomatia under in vitro conditions. Capsaicin at a concentration of 10(-4)M caused characteristic structural alterations in the giant serotonergic neurons but did not significantly influence serotonin immunoreactivity in the neurons. At the light-microscopic level, the most conspiciuous structural alterations were swelling of the cell bodies, which contained a swollen pale nucleus. Under the electron microscope, the nuclei, mitochondria and the cisternae of the endoplasmic reticulum were swollen in the capsaicin-affected metacerebral giant neurons. Electron-microscopic cytochemical techniques for calcium demonstration revealed electron-dense deposits in the swollen mitochondria and in the cisternae of the endoplasmic reticulum, suggesting an increased Ca2+ influx. The serotonergic metacerebral giant neurons could be labelled by cobalt (1mM) in the presence of capsaicin (10(-4)M) suggesting that capsaicin opens the cation chanels of the capsaicin-sensitive neuronal membrane. The morphological and cytochemical alterations induced by capsaicin in the serotonergic metacerebral giant neurons of Helix pomatia closely resemble those induced in sensory neurons of mammalian dorsal root ganglion.

Animals↗