Non-perikarial elements in the central nervous system ischaemia  Page description

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Details of project

  
Identifier
37885
Type K
Principal investigator Sándor, Péter
Title in Hungarian Non-perikariális elemek a központi idegrendszeri ischaemiában
Title in English Non-perikarial elements in the central nervous system ischaemia
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Clinical Research Dept. (Semmelweis University)
Participants Benyó, Zoltán
Erdos, Benedek
Krizbai, István Adorján
Lacza, Zsombor
Starting date 2002-01-01
Closing date 2006-12-31
Funding (in million HUF) 7.144
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
Az agyi vérellátási zavarok racionális terápiáj nem képzelhető el az agyi keringés szabályzásában részt vevő tényezők és mechanizmusok feltérképezése nélkül. Ezek kutatása során ezideig háttérbe szorult a non-perikariális elemek (axonok, endothelialis sejtek, vér-agy gát) agyi keringési hatásainak vizsgálata a vérvesztés, keringési shock, agyi érelzáródás, cukorbetegség során. Altatott állatokon, agykérgi mikroereken, végzett vizsgálataink e kérdéskörben a következő jelentősebb megállapításokhoz vezettek:(1) Normál artériás nyomás mellett a CO2 agyi áramlásfokozó hatása nitrogén monoxid szabadgyökök közvetítésével jön létre. (2) Súlyos vérnyomásesés okozta agyi ischemiában a CO2 klasszikus agyi értágító hatása megfordul, érszűkítő hatást vált ki. (3) Vérzéses shock dekompenzált fázisában a vér-agy gát áteresztővé válik, ennek oka az érfali endotelsejteket összetartó occludin és cadherin expresszió csökkenése. (4) Szomatikus fájdalomingerek hatására az agy regionális véráramlása nő, a teljes agyi vértérfogat nem változik. (5) Inzulin-rezisztens állapotban, mely növeli a stroke kialakulásának veszélyét, az agyi erek endotelium-függő vazodilatációja csökken, ez a ciklooxigenáz enzim által mediált folyamatok károsodásának a következménye,
Results in English
The role of non-perikaryal elements (axons, endothelial cells, blood-brain barrier) of the brain in the regulation of cerebral blood flow (CBF) is incomplete. In the present studies this question was investigated. Main findings: (1) Vasodilatory action of the CO2 in the cerebrovascular bed is mediated by nitric oxide /NO/ (2)In severe arterial hypotension, the classic cerebral vasodilatory effect of CO2 is reversed: increased paCO2 results in decreased CBF. (3) In hemorrhagic shock the blood-brain barrier function is lost as a result of reduced occludin and cadherin expression. (4) Painful somatic afferent stimulation results in a significant increase of the regional cerebral blood flow (thalamus, somatosensory cortex) while total cerebral blood volume remains unchanged. (5) Endothelium-dependent cerebral vasodilation is significantly reduced in insulin-resistant animals as a consequence of disturbed cyclooxigenase mediated processes. (6) The PARP enzyme plays an important role in the development of ischemic brain damage: selective blockade of PARP results in a significant decrease of the infarct area of the brain, both in the gray and white matter.
Full text http://real.mtak.hu/390/
Decision
Yes





 

List of publications

  
KIS, B., SNIPES, J.A., GASPAR, T., LENZSER, G., TULBERT, C.D., BUSIJA, D.W.:: Cloning of cyclooxigenase-1b (putative COX-s) in mouse., Inflamm Res 55(7):274-278, 2006
LACZA, Z., CSORDÁS, A., PANKOTAI, E., SÁRSZEGI, Z., CZIRÁKI, A., KOLLAI, M., SZABÓ, C.:: Human heart mitochondria do not produce nitric oxide, Shock 23(2): 228, 2005
PACHER, P., MABLEY, J:G:, SORIANO, F.G., LIAUDET, K., KOMJATI, K., SZABÓ, C.: Endothelial disfunction in aging animals: the role of poly(ADP Ribose)Polymerase activation, Brit.J.Pharmacol 135: 1347-1350, 2002
SZABÓ, C., ZANCHI, K., KOMJÁTI, K., PACHER, P., KROLEWSKI, A.S., QUIST, W.C., LoGERFO, F.W., HORTON, E.S, VEVES, A.: Poly(ADP Ribose)Polymerase is activated in subjects at risk if developing type 2 diabetes and is associated with impaired vascular reactivity, Circulation 106: 2680-2686, 2002
PACHER, P., LIAUDET, K., MABLEY, J.G, KOMJÁTI, K., SZABÓ, C.: Pharmacological inhibition of Poly(Adenosine Diphosphate Ribose)Polymerase may represent a novel therapeutic approach in chronic heart failure, J. Amer Coll Cardiol 45:1006-1016, 2002
LACZA, Z., PUSKAR, M., KIS, B., PERCIACCANTE, J.V., MILLER, A.W., BUSIJA, D.W.: Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to bradykinin, AM. J. Phisiol. Heart Circ.Physiol. 283:406-411, 2002
GASPAR, T., KIS, B., SNIPES, J.A., LENZSER G., MAYANAGI, K., BARI, F., BUSIJA, D.W.:: Transient glucose and amino acid deprivation induces delayed preconditioning in cultured rat cortical neurons., J Neurochem 98(2): 555-565, 2006
SHIMIZU, K., LACZA, Z., RAJAPAKSE, N., HORIGUCHI, T., SNIPES, J., BUSIJA,D.W.: MitoK(ATP) opener, diazoxide reduces neuronal damage after middle cerebral artery occlusion in the rat, AM. J. Phisiol. Heart Circ. Physiol. 283:1005-1011, 2002
SÁNDOR, P.:: Az agyi véráramlás szabályozása. A mikrokeringés regulációjának fő tényezői., Vascularis neurologia (Ed.: Nagy Zoltán) B+V Kiadó, Budapest, pp.30-46, 2006
ERDÖS, B., MILLER, A.W., BUSIJA, D.W.: Alteration in KATP and KCa channel function in cerebral arteries of insulin-, Am J Physiol Heart Circ Physiol 283:2472-2477, 2002
ERDÖS, B., MILLER, A.W., BUSIJA, D.W.: Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats, Am J Physiol Heart Circ Physiol 282:2060-2065, 2002
LACZA, Z., HORVÁTH, E., BUSIJA, D.W.: Neural stem cell transplantation in cold lesion: a novel approach for the investigation of brain trauma and repair, Brain Res Protoc 11: 145-154, 2003
ISHIGURO,M., LACZA, Z., HORVÁTH, E.M., JÁRAI, Z., SÁNDOR, P., BENYO, Z.: The cannabinoid receptor antagonist AM-251 enhances the cerebrocortical hyperemic response tohypoxia/hypercapnia, Federation of the American Societies of Experimental Biology, Washington D.C., USA, The Faseb Journal 18: A1193, 2004
LENZSÉR, G., KRIZBAI, I.A., FEKETE, ZS., SÁNDOR, P., KOMJÁTI, K.: Blood brain barrier (BBB) changes during permanent global cerebral ischemia, 4th Internat Congress of Pathophysiology, Budapest, Acta Phys Hung 89:(1-3), p.2o3, 2002
ERDÖS, B., LACZA, Z., TÓTH, I.E., SZELKE, E., MERSICH, T., KOMJÁTI,K., PALKOVITS, M., SÁNDOR, P.: Mechanism of pain-infuced local cerebral blood flow changes in the rat sensory cortex and thalamus, Brain Res 960:219-227, 2003
SÁNDOR, P., REIVICH, M., KOMJÁTI, K.: Significance of endogenous opioids in the maintenance of cerebral and spinal vascular CO2-sensitivity in deep hemorrhagic hypotension, Brain Res Bull 59:433-438, 2003
HORVÁTH, B., HRABÁK, A., KÁLDI, K., SÁNDOR, P., BENYÓ, Z.: Contribution of the heme oxygenase pathway to the maintenance of the hypothalamic blood flow during diminished NO synthesis, J Cereb Blood Flow Metab 23:653-657, 2003
LACZA, Z., DÉZSI, L., KÁLDI, K., HORVÁTH, E.M., SÁNDOR, P., BENYÓ,Z.: Prostacyclin -mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade, Life Sci 73:1141-1149, 2003
BUSIJA, D.W., LACZA, Z., RAJAPAKSE, N., SHIMIZU, K., KIS, B., BARI, F., DOMOKI, F., HORIGUCHI, T.: Targeting mitochondrial ATP-sensitive potassium channels - a novel approach to neuroprotection, Brain Res Rev, 2004
ERDÖS, B., SNIPES, J.A., MILLER, A.W., BUSIJA, D.W.: Cerebrovascular dysfunction in Zucker obese rats is mediated by oxidative stress and protein kinase C, Diabetes 53:1352-1359, 2004
ERDÖS, B., SIMANDLE, S.A., SNIPES, J.A., MILLER, A.W., BUSIJA, D.W.: Potassium channel dysfunction in cerebral arteries of insulin-resistant rats is mediated by reactive oxygen species, Stroke 35:964-969, 2004
KOMJÁTI, K.,MABLEY, J.G., VIRÁG, L., SOUTHAN, G.J., SALZMAN, A.L., SZABO, C.: Poly(ADP-ribose) polymerase inhibition protects neurons and the white matter and regulates the translocation of apoptosis-inducing factor in stroke, Int J Mol Med 13:373-382, 2004
LACZA, Z., HORN, T.F., SNIPES, J.A., ZHANG, J., ROYCHOWDHURY, S., HORVÁTH, E.M., FIGUEROA, J.P., SZABO, C., BUSIJA, D.W., KOLLAI, M.: Lack of mitochondrial nitric oxide production in the mouse brain, J Neurochem 90:942-951, 2004
ERDÖS, B., SNIPES, J.A., KIS,B., MILLER, A.W., BUSIJA, D.W.: Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance, Am J Physol 27:1456-1461, 2004
McCULLOCH, J., KOMJÁTI, K., VALERIANI, V., DEWAR, D.: Beyond neuroprotection: protection of axons and oligodendrocytes in cerebral ischemia, In: Cerebrovascular Disease.(Ed.: Pak H.Chan)Cambridge University Press, Cambridge, pp.401-415, 2002
SÁNDOR,P., BENYÓ,Z., ERDŐS,B., LACZA,Z., KOMJÁTI,K.: The Roy-Sherrington hypothensis: facts and surmises, In:Brain Activation and Cerebral Blood Flow Control. (Ed.:Minoru Tomita, Iwao Kano, Edith Hamel)Elsevier, Amsterdam, pp. 325-335, 2002
BENYÓ, Z., LACZA, Z., HORTOBÁGYI, T., GÖRLACH, C., SÁNDOR, P., WAHL,M.: Neuronal nitric oxide synthase in the cerebrovascular endothelium, In: Brain Activation and Cerebral Blood Flow Control.(Ed.: Minoru Tomita, Iwao Kanno, Edith Hamel)Elsevier, Amsterdam, pp.369-377, 2002
LACZA, Z., BUSIJA, D.W.: The mitochondrial respiratory chain increases DAF fluorescence independently from nitric oxide levels, Federation of the American Societies of Experimental Biology, Washington D.C., USA, The Faseb Journal 18(4): 859, 2004
KRIZBAI, I.A., SZATMÁRI, E., BAUER, H.C., KOMJÁTI, K., LENZSÉR, G., SÁNDOR,P.: Blood-Brain barrier changes during compensated and decompensated hemorrhagic shock, 5th Symp. on Signal Transduction in the Blood Brain Barriers, Pottsdam, Abstract of Papers, p.1., 2002
KOMJÁTI, K., JAGTAP, P., BALOGLU,E., VAN DUZER, J., SALZMAN, A., SZABÓ, C.: Poly(ADP-ribose) polymerase inhibition of stroke: establishment..., Annual Meeting of the Federation of the American Societies of Experimental Biology, New Orleans, FASEB J A599, 2002
KOMJÁTI, K., WILLIAMS, W., Van DUZER, J., SALZMAN, A., SZABÓ, C.: Effects of FP15, a potent peroxynitrite decomposition catalyst in a rat model ofmiddle cerebral artery (MCA) occlusion induced stroke, Annual Meeting of the Federation of the American Societies of Experimental Biology, New Orleans,FASEB J A972, 2002
KOMJÁTI, K., PACHER, J.G., MABLEY, A., VEVES, A., SZABÓ, C.: Evidence for poly(ADP-ribose) polymerase activation in the diabetic microvasculature, Annual Meeting of the Federation of the American Societies of Experimental Biology, New Orleans, FASEB J A237, 2002
PACHER, J.G., SORIANO, F.G., KOMJÁTI, K., MABLEY, A., SZABÓ, C.: Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation, Annual Meeting of the Federation of the American Societies of Experimental Biology, New Orleans, FASEB J A242, 2002
KOMJÁTI, K., JAGTAP, P., BALOGLU, E., VAN DUZER, J., SALZMAN, A., SZABÓ, C.: Poly(ADP-ribose) polymerase inhibition of stroke: establishment of the therapeutic window, Society for Neuroscience Meeting, Orlando, Neursci Abst 202.4, 2002
LACZA Z., HORVÁTH E., KOMJÁTI K., HORTOBÁGYI T., SZABÓ C., BUSIJA DW.:: PARP inhibition improves the effectiveness of neural stem cell implantation in experimental brain trauma, Int J Mol Med 12:155–159, 2003
BUSIJA, D.W., SHIMIZU, K., LACZA, ZS., RAJAPAKSE, T., HORIGUCHI, T., SNIPES, J.A.: Mitochondrial ATP-sensitive potassium opener diazoxide reduces neuronal damage after ischemia in rats, 4th Internat Congress of Pathophysiology, Budapest, Acta Phys Hung 89: (1-3), p.195, 2002
BENYÓ, Z., LACZA, ZS., HERMÁN, P., GÖRLACH, T., HORTOBÁGYI, T., SÁNDOR, P., WAHL, M.: Interplay between cyclic GMP- and thromboxane receptor- mediated mechanisms in the rat middle cerebral artery (MCA), 4th Internat. Congress of Pathophysiology, Budapest, Acta Phys Hung 89: (1-3), p.56, 2002
HORVÁTH, B., HRABÁK, A., KÁLDY, K., JOHNSON, F.K., SÁNDOR, P., BENYÓ, Z.: The role of endogenous carbon monoxide (CO) and its interaction with nitric oxide (NO) in the cerebral circulation, 4th Internat Congress of Pathophysiology, Budapest, Acta Phys Hung 89: (1-3), p.124, 2002
ERDÖS, B., MILLER, A.W., BUSIJA, D.W.: Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin resistant rats, Federation of the American Society of Experimental Biology Meeting, New Orleans, FASEB J 16, A1123, 2002
ERDÖS, B., MILLER, A.W., BUSIJA, D.W.: Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin resistant rats, 4th Internat Congress of Pathophysiology, Budapest, Acta Phys Hung 89: (1-3), p.55, 2002
LACZA, Z., SNIPES, J.A., RAJAPAKSE, T., KIS, B., BUSIJA, D.W.: Characterization of the mithochondrial ATP-dependent K-channel, 4th Internat Congress of Pathophysiology, Budapest, Acta Phys Hung 89: (1-3), p.2o2, 2002
LENZSÉR, G., KRIZBAI, A., FEKETE, ZS., WAPPLER, E., SÁNDOR, P., KOMJÁTI, K.: A vér-agy gát strukturális és funkcionális változásai permanens globális agyi ischemia folyamán, Magyar Élettani Társaság LXVII. Vándorgyülése, Pécs, Előadáskivonatok, p.82, 2003
LENZSÉR, G., HERMÁN, P., SÁNDOR, P., BENYÓ, Z.: .: Nitric oxide synthase blockade sensitizes the cerebral circulation to thromboxane-induced CBF oscilations, 18th IMSS Congress, Istambul, Abstract Book, p.174, 2003
HORTOBÁGYI, L., HORVÁTH, B., HRABÁK, A., SÁNDOR, P., BENYÓ, Z.: A nitrogén monoxid szintáz (NOS) és a ciklooxigenáz (COX) reakcióutak kölcsönhatása a hypothalamus véráramlásának szabályozásában, Magyar Élettani Társaság LXVII. Vándorgyülése, Pécs, Előadáskivonatok, p.82, 2003
LENZSÉR, G., KRIZBAI, I., FEKETE, ZS., WAPPLER, E., SÁNDOR, P., KOMJÁTHY, K.: A vér agy-gát strukturális és funkcionális változásai permanens globális agyi ischemia folyamán, Magyar Stroke Társaság VI. nemzetközi Kongresszusa, Zalakaros, Elöadáskivonatok, p.85, 2003
LENZSÉR, G., HERMÁN, P., KOMJÁTHY, K., SÁNDOR, P., BENYÓ, Z.: Nitric oxide synthase blockade sensitizes the cerebrocortical circulation to thromboxane-induced CBF oscillations, “Brain o3, Barin PET o3“ Calgary, Canada, J Cereb Blood Flow Metabol 23 (suppl.1): 65, 2003
HORVÁTH, B., ISHIGURO, M., HRABÁK, A., KÁLDI, K., LACZA, Z., SÁNDOR, P., BENYÓ, Z.: Interaction between the heme oxigenase and nitric oxide synthase pathways in the regulation of the resting CBF, Brain o3, Brain PET o3, Calgary, Canada, J Cerebr Blood Flow Metabol 23(suppl.1.): 65, 2003
LACZA, Z., SNIPES, J.A., PANKOTAI, E., KOLLAI, M., BUSIJA, D.W., SZABÓ, C.: Isolation of ATP-dependent potassium subunits in heart and brain mitochondria, 68th Annual Meeting of the Hungarian Physiological Society, Debrecen, Proceedings, p. 141, 2004
HORVÁTH, B., ISHIGURO, M., LENZSÉR, G., HERMÁN, P., HRABÁK, A., KÁLDI, L., SÁNDOR, P., BENYO, Z.: Interaction between the heme oxygenase (HO) and NO synthase pathways in the regulation of the resting CBF, Federation of the American Societies of Experimental Biology, Washington D.C., USA, The Faseb Journal 18:A268, 2004
HORVÁTH, E.M., LACZA, Z., KOLLAI, M., BUSIJA, D.W.: Evidence for fusion between stem cells and host cells in the penumbra region of experimental brain trauma, IBRO International Workshop on Neuronal Circuits: from Elementary to Complex Functions, Budapest, Proceedings in: Ideggyógyászati Szemle (Clinical Neuroscience) 57, 2004
HORVÁTH, E.M., LACZA, Z., HORN, T.W.F., ROYCHOWDHURRY, S., ZHANG, J., FIGUEROA, J.P., SZABO, C., KOLLAI, M., BUSIJA, D.W.: Isolation of ATP-dependent potassium channel subunits in heart and brain mitochondria, 68th Annual Meeting of the Hungarian Physiological Society, Debrecen, Proceedings, p.156, 2004
HORVÁTH, E.M., LACZA, Z., KOLLAI, M., BUSIJA, D.W.: Evidence for fusion between stem cells and host cells in the penumbra region of experimental brain trauma, Magyar Idegtudományi Társaság Vándorgyýlése, Budapest, 2004
LACZA, Z., HORN TWF., ROYCHOWDHURY, S., KIS, B., HORVÁTH, E.M., SZABÓ, C., BUSIJA, D.W.: Mitochondria produce peroxynitrite rather than nitric oxide in the brain, IBRO International Workshop on Neuronal Circuits: from Elementary to Complex Functions, Budapest, Proceedings in: Ideggyógyászati Szemle (Clinical Neuroscience) 57: A 38, 2004
LACZA, Z., HORN, T.W.F., SNIPES, J.A., HORVÁTH, E.M.., ROYCHOWDHURY, S., ZHANG, J., FIGUEROA, J.P., SZABÓ, C., BUSIJA, D.W.: Mitochondrial NO and reactive nitrogen production: Does mtNOS exist?, The 3rd International Conference on the Biology, Chemistry and Therapeutic Applications on Nitric Oxide, Atlanta, USA, Proceedings, p.56, 2004
LACZA, Z., ROYCHOWDHURY, S., HORVÁTH, E.M., KIS, B., HORN, T.W.F., BUSIJA, D.W.: Lack of mitochondrial nitric oxide production in the brain, Federation of the American Societies of Experimental Biology, Washington D.C., USA, The Faseb Journal 18: A1193, 2004
LACZA, Z., SNIPES, J.A., KOLLAI, M., SZABO, C., BUSIJA, D.W.: The mitochondrial ATP-dependent potassium channel: a novel drug target for ischemic cardioprotection, Annual Meeting of the Hungarian Society of Cardiologists, Balatonfüred, Cardiol Hung 34: C66, 2004
LACZA, ZS., SNIPES, J. A., PANKOTAI, E., KOLLAI, M., BUSIJA, D.W., SZABO, CS.: ATP-függő K-csatorna alegységek azonosítása szív és agy mitochondriumokban, Magyar Élettani Társaság 68. Vándorgyılése, Debrecen, 2004
LACZA, Z., PUSKAR, M., BUSIJA, D.W.: Urotensin II is an NO-dependent vasodilator in the piglet pial vasculature, Federation of the American Societies of Experimental Biology, Washington D.C., USA, The Faseb Journal 18(4): 199.13, 2004
LENZSÉR, G., KIS, B., BARI, F., BUSIJA, D.W.:: Diazoxide preconditioning attenuates global cerebral ischemia-induced blood-brain barrier permeability, Brain Res 1051:72-80, 2005
KRIZBAI, I., LENZSÉR, G., SZATMÁRI, E., FARKAS, A.E., WILHELM, M.I., FEKETE, Z., ERDŐS, B., BAUER, H., BAUER, H-C., SÁNDOR, P., KOMJÁTI, K.:: Blood-brain barrier changes during compensated and decompensated hemorrhagic shock., Shock 24(5): 428-433, 2005
SZELKE, E., VÁRBÍRÓ, SZ., MERSICH, T., BÁNHIDY, F., SZÉKÁCS, B., SÁNDOR, P., KOMJÁTI, K.:: Effects of estrogen and progestin on hypothalamic blood flow autoregulation, J Soc Gynecol Investig 12(8): 604-609, 2005
ISHIGURO, M., HORVÁTH, B., HORVÁTH, E.M., LENZSÉR, G., HERMÁN, P., SÁNDOR, P., BENYÓ, Z.:: Effects of hem-oxygenase blockade ont he cerebral circulation, 67th Annual Meting of the Hungarian Physiological Society, Budapest; Acta Phys Hung 92(3-4): 264, 2005
BENYÓ, Z., GILLE, A., KERO, J., CSIKY, M., SUCHANKOVA, N.C., NÜSSIG, R.M., MOERS, A., PFEFFER, K., OFFERMANS, K.:: GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing, J Clin Invest 115:3634-3640, 2005
SHIMIZU k., MILLER AW., ERDOS B., BARI F., BUSIJA DW.:: Role of endothelium in hyperemia during cortical spreading depression (CSD) in the rat, Brain Res 928: 40–49, 2002
HORTOBAGYI, L., KIS, B., HRABÁK, A., HORVÁTH, B., HUSZTY, G., SCHWEER, H., BENYÓ, B., SÁNDOR, P., BUSIJA, D.W., BENYÓ, Z.:: Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids., Brain Res 1131:129-137, 2007
LENZSER, G., KIS, B,. SNIPES, J.A., GASPAR, T., SÁNDOR, P,. KOMJÁTI K,. SZABÓ, C,. BUSIJA, D,W.:: Contribution of poly(ADP-ribose)polymerase to postischemic blood-brain barrier damage in rats., J Cereb Blood Flow Metabol (advance online publication doi10.1038sj.cbfm.9600437, p.1-9, 10 January,), 2007
MERSICH, T., SZELKE, E., ERDŐS, B., LACZA, Z., KOMJÁTI, K., SÁNDOR, P.:: Somatosensory pain does not affect total cerebral blood volume., Neuroreport, 00: 1-4. (accepted for publication 9. January), 2007



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