creators_name: Gonzalez-Falcon, Armando
creators_name: Candelario-Jalil, Eduardo
creators_name: Garcia-Cabrera, Michel
creators_name: Leon, Olga S.
type: journalp
datestamp: 2007-08-20
lastmod: 2011-03-11 08:56:56
metadata_visibility: show
title: Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats
ispublished: pub
subjects: neuro-chem
full_text_status: public
keywords: pyruvate; middle cerebral artery occlusion; neuroprotection; stroke; rat; neurological deficits; cerebral ischemia
abstract: Recent experimental evidences indicate that pyruvate, the final metabolite of glycolysis, has a remarkable protective effect against different types of brain injury. The purpose of this study was to assess the neuroprotective effect and the neurological outcome after pyruvate administration in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in rats. Three doses of pyruvate (250, 500 and 1000 mg/kg, i.p.) or vehicle were administered intraperitoneally 30 min after pMCAO. In other set of experiments, pyruvate was given either before, immediately after ischemia or in a long-term administration paradigm. Functional outcome, mortality and infarct volume were determined 24 h after stroke. Even when the lowest doses of pyruvate reduced mortality and neurological deficits, no concomitant reduction in infarct volume was observed. The highest dose of pyruvate increased cortical infarction by 27% when administered 30 min after pMCAO. In addition, when pyruvate was given before pMCAO, a significant increase in neurological deficits was noticed. Surprisingly, on the contrary of what was found in the case of transient global ischemia, present findings do not support a great neuroprotective role for pyruvate in permanent focal cerebral ischemia, suggesting two distinct mechanisms involved in the effects of this glycolytic metabolite in the ischemic brain.
date: 2003-11
date_type: published
publication: Brain Research
volume: 990
number: 1-2
publisher: Elsevier
pagerange: 1-7
refereed: TRUE
referencetext: [1]	J.M. Braughler, E.D. Hall, Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Radic. Biol. Med. 6 (1989) 289-301. 

[2]	D.W. Choi, Calcium: still center-stage in hypoxic-ischemic neuronal death, Trends Neurosci. 18 (1995) 58-60.

[3]	D.W. Choi, J.Y. Koh, Zinc and brain injury, Annu. Rev. Neurosci. 21 (1998) 347-375.

[4]	D.W. Choi, S.M. Rothman, The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death, Annu. Rev. Neurosci. 13 (1990) 171-182.

[5]	W. Danysz, A.C. Parsons, Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications, Pharmacol. Rev. 50 (1998) 597-664.

[6]	R. Davenport, M. Dennis, Neurological emergencies: acute stroke, J. Neurol. Neurosurg. Psychiatry 68 (2000) 277-288. 

[7]	G. del Zoppo, I. Ginis, J.M. Hallenbeck, C. Iadecola, X.Wang, G.Z. Feuerstein, Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia, Brain Pathol. 10 (2000) 95-112.

[8]	S. Desagher, J. Glowinski, J. Premont, Pyruvate protects neurons against hydrogen peroxide-induced toxicity, J. Neurosci. 17 (1997) 9060-9067.

[9]	A. Doerfler, S. Schwab, T.T. Hoffmann, T. Engelhorn, M. Forsting, Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats, Stroke 32 (2001) 2675-2681.

[10]	L.L. Dugan, D.W. Choi, Hypoxic-ischemic brain injury and oxidative stress. In: G.J. Siegel, B.W. Agranoff, R.W. Albers, S.K. Fisher, M.D. Uhler (Eds.), Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Lippincott-Raven Publishers, Philadelphia, 1999, pp. 711-729.

[11]	Edaravone Acute Infarction Study Group, Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters, Cerebrovasc. Dis. 15 (2003) 222-229.

[12]	M. Fisher, Neuroprotection of acute ischemic stroke: where are we?, Neuroscientist 5 (1999) 392-401.

[13]	M. Fisher, Stroke Therapy. 2nd Edition. Butterworth Heineman, 2001.


[14]	F. Funk, J.P. Lenders, R.R. Crichton, W. Schneider, Reductive mobilisation of ferritin iron, Eur. J. Biochem. 152 (1985)167-172.

[15]	W. Hacke, S. Schwab, M Horn, M. Spranger, M. De Georgia, R. von Kummer, The “malignant” middle cerebral artery territory infarction: clinical course and prognostic signs, Arch. Neurol. 53 (1996) 309-315. 


[16]	G.J. Hankey, Stroke: how large a public health problem, and how can the neurologist help?, Arch. Neurol. 56 (1999) 748-754.

[17]	J. Honkaniemi, S.M. Massa, M. Breckinridge, F.R. Sharp, Global ischemia induces apoptosis-associated genes in hippocampus, Brain Res. Mol. Brain Res. 42 (1996) 79-88.

[18]	A.J. Hunter, K.B. Mackay, D.C. Rogers, To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents?, Trends Pharmacol. Sci. 19 (1998) 59-66.

[19]	C. Iadecola, M. Alexander, Cerebral ischemia and inflammation, Curr. Opin.  Neurol. 14 (2001) 89-94.

[20]	H. Kassem-Moussa, C. Graffagnino, Nonocclusion and spontaneous recanalization rates in acute ischemic stroke: a review of cerebral angiography studies, Arch. Neurol. 59 (2002) 1870-1873.

[21]	Y. H. Kim, E.Y. Kim, B.J. Gwag, S. Sohn, J.Y. Koh, Zinc-induced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals, Neuroscience 89 (1999) 175-182.

[22]	J. Koizumi, Y. Yoshida, T. Nakazawa, G. Ooneda, Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area, Jpn. J. Stroke 8 (1986) 1-8.

[23]	J.Y. Lee, Y.H. Kim, J.Y. Koh, Protection by pyruvate against transient forebrain ischemia in rats, J. Neurosci. 21 (2001) RC171.

[24]	Q. Li, D. Stephenson, Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat, Exp. Neurol. 177 (2002) 531-537.

[25]	Y. Liu, L. Belayev, W. Zhao, R. Busto, M.D. Ginsberg, MRZ 2/579, a novel uncompetitive N-methyl-D-aspartate antagonist, reduces infarct volume and brain swelling and improves neurological deficits after focal cerebral ischemia in rats, Brain Res. 862 (2000) 111-119.

[26]	D. Lobner, L.M. Canzoniero, P. Mancera, F. Gottron, H. Ying, M. Knudson, M. Tian, L.L. Dugan, G.A. Kerchner, C.T. Sheline, S.J. Korsmeyer, D.W. Choi, Zinc-induced neuronal death in cortical neurons, Cell. Mol. Biol. 46 (2000) 797-806.

[27]	E.Z. Longa, P.R. Weinstein, S. Carlson, R. Cummins, Reversible middle cerebral artery occlusion without craniectomy in rats, Stroke 20 (1989) 84-91.

[28]	S. Love, Oxidative stress in brain ischemia, Brain Pathol 9 (1999) 119-131.

[29]	M. Maus, P. Marin, M. Israel, J. Glowinski, J. Premont, Pyruvate and lactate protect striatal neurons against N-methyl-D-aspartate-induced neurotoxicity, Eur. J.  Neurosci. 11 (1999) 3215-3224.

[30]	E. Mazzio, K.F. Soliman, Pyruvic acid cytoprotection against 1-methyl-4-phenylpyridinium, 6- hydroxydopamine and hydrogen peroxide toxicities in vitro, Neurosci. Lett. 337 (2003) 77-80.

[31]	E. Mazzio, K.F. Soliman, Cytoprotection of pyruvic acid and reduced beta-nicotinamide adenine dinucleotide against hydrogen peroxide toxicity in neuroblastoma cells, Neurochem. Res. 28 (2003) 733-741. 

[32]	K. Minematsu, L. Li, C.H. Sotak, M.A. Davis, M. Fisher, Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats, Stroke 23 (1992) 1304-1310.

[33]	P.D. Mongan, J.L. Fontana, R. Chen, R. Bünger, Intravenous pyruvate prolongs survival during hemorrhagic shock in swine, Am. J. Physiol. Heart Circ. Physiol. 277 (1999) H2253–H2263.

[34]	P.D. Mongan, J. Capacchione,  J.L. Fontana, S. West, R. Bünger, Pyruvate improves cerebral metabolism during hemorrhagic shock. Am. J. Physiol. Heart Circ. Physiol. 281 (2001) H854–H864.

[35]	P. Muntner, E. Garrett, M.J. Klag, J. Coresh, Trends in stroke prevalence between 1973 and 1991 in the US population 25 to 74 years of age, Stroke 33 (2002) 1209-1213.

[36]	C.J. Murray, A.D. López,  Mortality by cause for eight regions of the world: Global burden of Disease Study, Lancet 349 (1997) 1269-1276. 

[37]	N. Nagai, M. De Mol, B. Van Hoef, M. Verstreken, D. Collen, Depletion of circulating alpha(2)-antiplasmin by intravenous plasmin or immunoneutralization reduces focal cerebral ischemic injury in the absence of arterial recanalization, Blood 97 (2001) 3086-3092.

[38]	S. Namura, J. Zhu, K. Fink, M. Endres, A. Srinivasan, K.J. Tomaselli, J. Yuan, M.A. Moskowitz, Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia, J. Neurosci. 18 (1998) 3659-3668.

[39]	A. Ogawa, T. Yoshimoto, H. Kikuchi, K. Sano, I. Saito, T. Yamaguchi, H. Yasuhara, Ebselen in acute middle cerebral artery occlusion: a placebo-controlled, double blind clinical trial. Cerebrovasc. Dis. 9 (1999) 112-118.

[40]	P. Pantano, F. Caramia, L. Bozzao, C. Dieler, R. von Kummer, Delayed increase in infarct volume after cerebral ischemia: correlation with thrombolytic treatment and clinical outcome, Stroke 30 (1999) 502-507.

[41]	J.A. Park, J.Y. Lee, T.A. Sato, J.Y. Koh, Co-induction of p75NTR and p75NTR-  associated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat, J. Neurosci. 20 (2000) 9096-9103.

[42]	R.C. Poole, A.P. Halestrap, Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264 (1993) C761-C782. 

[43]	N. Ramakrishnan, R. Chen, D.E. McClain, R. Bunger, Pyruvate prevents hydrogen peroxide-induced apoptosis, Free Radic. Res. 29 (1998) 283-295.

[44]	A. Rami, R. Agarwal, G. Botez, J. Winckler, mu-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage, Brain Res. 866 (2000) 299-312.

[45]	D. Reglodi, A. Somogyvari-Vigh, S. Vigh, T. Kozicz, A. Arimura,  Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in the rat, Stroke 31 (2000) 1411-1417.

[46]	S. Rehncrona, H.N. Hauge, B.K. Siesjo, Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2, J. Cereb. Blood Flow Metab. 9 (1989) 65-70.

[47]	F. Ruiz, G. Alvarez, R. Pereira, M. Hernandez, M. Villalba, F. Cruz, S. Cerdan, E. Bogonez, J. Satrustegui, Protection by pyruvate and malate against glutamate-mediated neurotoxicity, Neuroreport 9 (1998) 1277-1282.

[48]	S.L. Sensi, H.Z. Yin, J.H. Weiss, AMPA/kainate receptor-triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction, Eur. J. Neurosci. 12 (2000) 3813-3818.

[49]	C.T. Sheline, M.M. Behrens, D.W. Choi, Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD(+) and inhibition of glycolysis, J. Neurosci. 20 (2000) 3139-3146.

[50]	A. Shuaib, C. Xu Wang, T. Yang, R. Noor, Effects of nonpeptide V(1) vasopressin receptor antagonist SR-49059 on infarction volume and recovery of function in a focal embolic stroke model, Stroke 33 (2002) 3033-3037.

[51]	B. K. Siesjo, G. Bendek, T. Koide, E. Westerberg, T. Wieloch, Influence of acidosis on lipid peroxidation in brain tissues in vitro, J. Cereb. Blood Flow Metab. 5 (1985) 253-258.

[52]	Stroke Therapy Academy Industry Roundtable (STAIR II), Recommendation for clinical trial evaluation of acute stroke therapies, Stroke 32 (2001) 1598-1606.

[53]	J. H. Weiss, S.L. Sensi, J.K. Koh, Zn(2+): a novel ionic mediator of neural injury in brain disease, Trends Pharmacol. Sci. 21 (2000) 395-401.

[54]	Y. Yang, Q. Li, H. Miyashita, W. Howlett, M. Siddiqui, A. Shuaib, Usefulness of postischemic thrombolysis with or without neuroprotection in a focal embolic model of cerebral ischemia, J. Neurosurg. 92 (2000) 841-847.

[55]	Y. Yang, A. Shuaib, Q. Li, Quantification of infarct size on focal cerebral ischemia model of rats using a simple and economical method, J. Neurosci.  Methods 84 (1998) 9-16.

[56]	H.Z. Yin, S.L. Sensi, F. Ogoshi, J.H. Weiss, Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation- induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons, J. Neurosci. 22 (2002) 1273-1279.

[57]	Q. Zhang, G. Zhang, F. Meng, H. Tian, Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated by Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involving oxidative stress following brain ischemia in rat hippocampus, Neurosci. Lett. 337 (2003) 51-55.

[58]	Z. Zhao, M. Cheng, K.R. Maples, J.Y. Ma, A.M. Buchan, NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat, Brain Res. 909 (2001) 46-50.

citation:   Gonzalez-Falcon, Armando and Candelario-Jalil, Eduardo and Garcia-Cabrera, Michel and Leon, Olga S.  (2003) Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats.  [Journal (Paginated)]     
document_url: http://cogprints.org/5652/1/pyruvate_in_stroke_Brain_Res_2003.pdf