Skip to main content

Advertisement

SpringerLink
Log in

Tenoxicam Exerts a Neuroprotective Action after Cerebral Ischemia in Rats

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

In this study we investigated the effects of Tenoxicam, a type 2 cyclooxygenase (COX-2) inhibitor, on brain damage induced by ischemia-reperfusion. Male Wistar rats (18-month old average) were anesthetized and submitted to ischemia occlusion of both common carotid arteries (BCAO) for 45 min. After 24 h of reperfusion, rats were decapitated and hippocampi removed for further assays. Animals were divided into sham-operated, ischemia, ischemia + Tenoxicam 2.5 mg/kg, and ischemia + Tenoxicam 10 mg/kg groups. Tenoxicam was administered intraperitoneally immediately after BCAO. Histological analyses show that ischemia produced significant striatal as well as hippocampal lesions which were reversed by the Tenoxicam treatment. Tenoxicam also significantly reduced, to control levels, the increased myeloperoxidase activity in hippocampus homogenates observed after ischemia. However, nitrite concentrations showed only a tendency to decrease in the ischemia + Tenoxicam groups, as compared to that of ischemia alone. On the other hand, hippocampal glutamate and aspartate levels were not altered by Tenoxicam. In conclusion, we showed that ischemia is certainly related to inflammation and to increased free radical production, and selective COX-2 inhibitors might be neuroprotective agents of potential benefit in the treatment of cerebral brain ischemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • R. Ross (1999) ArticleTitleAtherosclerosis–an inflammatory disease [review] New Engl. J. Med. 340 IssueID2 115–126 Occurrence Handle10.1056/NEJM199901143400207

    Article  Google Scholar 

  • K. Becker D. Kindrick J. Relton J. Harlan R. Winn (2001) ArticleTitleAntibody to the α4 integrin decreases infarct size in transient focal cerebral ischemia in rats Stroke 32 206–211

    Google Scholar 

  • M. Campanella C. Sciorati G. Tarozzo M. Beltramo (2002) ArticleTitleFlow cytometric analysis of inflammation cells in schemic rat brain Stroke 33 586–592 Occurrence Handle10.1161/hs0202.103399

    Article  Google Scholar 

  • J.H. Garcia K.F. Liu Y. Yoshida J. Lian S. Chen G.J. Del Zoppo (1994) ArticleTitleInflux of leukocytes and platelets in an evolving brain infarct (Wistar rats) Am. J. Pathol. 144 IssueID1 188–199

    Google Scholar 

  • B. Lin M. D. Gisnberg R. Busto L. Li (2000) ArticleTitleHyperglycemia triggers massive neutrophil deposition in brain following transient ischemia in rats Neurosci. Lett. 278 1–4 Occurrence Handle10.1016/S0304-3940(99)00889-7

    Article  Google Scholar 

  • T. Sairanen A. Ristimaki M. L. Karjalainen-Lindsberg (1998) ArticleTitleCyclooxygenase-2 is induced globally in infarcted human brain Ann. Neurol. 43 738–747 Occurrence Handle10.1002/ana.410430608

    Article  Google Scholar 

  • U. Dirnagl C. Iadecola M. A. Moskowitz (1999) ArticleTitlePathobiology of ischaemic stroke: an integrated view Trends Neurosci. 22 IssueID9 391–397 Occurrence Handle10.1016/S0166-2236(99)01401-0

    Article  Google Scholar 

  • C. Iadecola (1999) Mechanisms of cerebral ischemic damage W. Walz (Eds) Cerebral Ischemia: Molecular and Cellular Pathophysiology Humana Press New Jersey 3–32

    Google Scholar 

  • P. Lipton (1999) ArticleTitleIschemic cell death in brain neurons Physiol. Rev. 79 IssueID4 1431–1568

    Google Scholar 

  • S. Love (1999) ArticleTitleOxidative stress in brain ischemia Brain Pathol. 9 IssueID1 119–131

    Google Scholar 

  • B. K. Siesjö P. Siesjö (1996) ArticleTitleMechanisms of secondary brain injury Eur. J. Anesthesiol. 13 IssueID3 247–268 Occurrence Handle10.1046/j.1365-2346.1996.00976.x

    Article  Google Scholar 

  • N. R. Sims E. Zaidan (1995) ArticleTitleBiochemical changes associated with selective neuronal death following short-term cerebral ischemia Int. J. Biochem. Cell Biol. 27 IssueID6 531–550 Occurrence Handle10.1016/1357-2725(95)00026-L

    Article  Google Scholar 

  • J. De Alba A. Cárdenas M. A. Moro J. C. Leza P. Lorenzo I. Lizasoain (1999) ArticleTitleUse of brain slices in the study of pathogenic role of inducible nitric oxide synthase in central ischemia-reperfusion Gen. Pharmacol. 32 577–581 Occurrence Handle10.1016/S0306-3623(98)00280-8

    Article  Google Scholar 

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

    Google Scholar 

  • C. Iadecola F. Zhang R. Casey H.B. Clark M. E. Ross (1996) ArticleTitleInducible nitric oxide synthase gene expression in vascular cells after transient focal cerebral ischemia Stroke 27 IssueID8 1373–1380

    Google Scholar 

  • M. Nagayama K. Niwa T. Nagayama M. E. Ross C. Iadecola (1999) ArticleTitleThe cyclooxygenase-2 inhibitor NS–398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene J. Cereb. Blood Flow Metab. 19 1213–1219 Occurrence Handle10.1097/00004647-199911000-00005

    Article  Google Scholar 

  • S. Govoni E. Masoero L. Favalli A. Rozza R. Scelsi S. Viappiani C. Buccellati A. Sala G. Folco (2001) ArticleTitleThe cyclooxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat Neurosci. Lett. 303 91–94 Occurrence Handle10.1016/S0304-3940(01)01675-5

    Article  Google Scholar 

  • L. McCullough L. Wu N. Haughey X. Liang T. Hand Q. Wang R. M. Breyer K. Andreasson (2004) ArticleTitleNeuroprotective function of the PGE2 EP2 receptor in cerebral ischemia J. Neurosci. 24 257–268 Occurrence Handle10.1523/JNEUROSCI.4485-03.2004

    Article  Google Scholar 

  • T. Takadera H. Yumoto Y. Tozuka T. Ohyashiki (2002) ArticleTitleProstaglandin E(2) induces caspase-dependent apoptosis in rat cortical cells Neurosci. Lett. 317 61–64 Occurrence Handle10.1016/S0304-3940(01)02449-1

    Article  Google Scholar 

  • Y. Matsuo T. Kihara M. Ikeda M. Ninomiya H. Onodera K. Kogure (1996) ArticleTitleRole of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain Brain Res. 709 296–302 Occurrence Handle10.1016/0006-8993(95)01324-5

    Article  Google Scholar 

  • K. Nishigaya Y. Yoshida M. Sasuga H. Nukui G. Ooneda (1991) ArticleTitleEffect of recirculation on exacerbation of ischemic vascular lesions in rat brain Stroke 22 635–642

    Google Scholar 

  • H. C. A. Emsley P. J. Tyrrell (2002) ArticleTitleInflammation and infection in clinical stroke J Cereb. Blood Flow Metab. 22 1399–2419 Occurrence Handle10.1097/00004647-200212000-00001

    Article  Google Scholar 

  • W. C. Jean S. R. Spellman E. S. Nussbaun W. C. Low (1998) ArticleTitleReperfusion injury after focal cerebral ischemia: role of inflammation and the therapeutic horizon [review] Neurosurgery 43 1382–1397

    Google Scholar 

  • P. J. Lindsberg R. O. Roine T. Tatlisumak T. Sairanen M. Kaste (2000) ArticleTitleStroke: the future of stroke treatment Neurol. Clinics 18(2) 495–510

    Google Scholar 

  • M. Fisher T. G. Brott (2003) ArticleTitleEmerging therapies for acute ischemic stroke-new therapies on trial Stroke 34 359–361 Occurrence Handle10.1161/01.STR.0000054627.69159.C2

    Article  Google Scholar 

  • L. Pantoni C. Sarti D. Inzitori (1998) ArticleTitleCytokines and cell adhesion molecules in cerebral ischemia experimental bases and therapeutic perspectives Arterioscler. Thromb. Vasc. Biol. 18 503–513

    Google Scholar 

  • D. Myron M. D. Ginsberg (2003) ArticleTitleAdventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection Stroke 34 214–223 Occurrence Handle10.1161/01.STR.0000048846.09677.62

    Article  Google Scholar 

  • E. Candelario-Jalil A. Gonzalez-Falcon M. Garcia-Cabrera D. Alvarez S. Al-Dalain G. Martinez O. S. Leon J. E. Springer (2003) ArticleTitleAssessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia J. Neurochem 86 545–555 Occurrence Handle10.1046/j.1471-4159.2003.01812.x

    Article  Google Scholar 

  • M. Myrjany L. Ho G. M. Pasinetti (2002) ArticleTitleRole of cyclooxygenase-2 in neuronal cell cycle activity andglutamate-mediated excitotoxicity J. Pharmacol. Exp. Ther. 301 494–500 Occurrence Handle10.1124/jpet.301.2.494

    Article  Google Scholar 

  • T. Sasaki J. Hamada M. Shibata N. Araki Y. Fukuuchi (2001) ArticleTitleInhibition of nitric oxide production during global ischemia ameliorates ischemic damage of pyramidal neurons in the hippocampus Keio J. Med. 50(3) 182–187

    Google Scholar 

  • Y. Manabe J. Anrather T. Kawano K. Niwa P. Zhou M. E. Ross C. Iadecola (2004) Prostanoids, not reactive oxygen species, mediate COX-2-dependent neurotoxicity Ann. Neurol. 55–668

    Google Scholar 

  • P. P. Bradley D. A. Priebat R. D. Christensen G. Rothstein (1982) ArticleTitleMeasurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker J. Invest. Dermatol. 78 206–209 Occurrence Handle10.1111/1523-1747.ep12506462

    Article  Google Scholar 

  • J. E. Krawisz P. Sharon W. F. Stenson (1984) ArticleTitleQuantitative assay for acute intestinal inflammation based on myeloperoxidase activity Gastroenterol. 87 1344–1350

    Google Scholar 

  • P. Lindroth K. Mopper (1979) ArticleTitleHigh performance liquid chromatographic determination on subpicomole amounts of amino acids by precolumn fluorescence derivatization with O-phtaldialdehyde Anal. Chem. 51 1667–1674

    Google Scholar 

  • G. Paxinos C. Watson (1986) The Rat Brain in Stereotaxic Coordinates, 2 nd ed Academic Press Sydney

    Google Scholar 

  • B. K. Sharma K. Kumar (1998) ArticleTitleRole of proinflammatory cytokines in cerebral ischemia: a review Metabol. Brain Dis. 13 1–8 Occurrence Handle10.1023/A:1020670610512

    Article  Google Scholar 

  • S. Cuzzocrea M.C. McDonald E. Mazzon D. Siriwardena G. Constantino F. Fulia G. Cuccinota E. Gitto S. Cordano I. Barberi A. De Sarro A.P. Caputi C. Thiemermann (2000) ArticleTitleEffects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury Brain Res. 875 96–106 Occurrence Handle10.1016/S0006-8993(00)02582-8

    Article  Google Scholar 

  • I. S. Hwang C. Y. Shin Y. Huh J. H. Ryu (2002) ArticleTitleHwangryun-Hae-Dok-Tang (Huanglian-Jie-Du-Tang) extract and its constituents reduce ischemia-reperfusion brain injury and neutrophil infiltration in rats Life Sci. 71 2105–117 Occurrence Handle10.1016/S0024-3205(02)01920-3

    Article  Google Scholar 

  • M. Weaver K. Leshley H. Sands K. R. Gritman J. L. Legos R. F. Tuma (2002) ArticleTitleLEX032, a novel recombinant serpin, protects the brain after transient focal ischemia Microvasc. Res. 63 327–334 Occurrence Handle10.1006/mvre.2002.2405

    Article  Google Scholar 

  • Y. Yamasaki Y. Matsuo J. Zagorski M. Matsuura H. Onodera Y. Itoyama K. Kogure (1997) ArticleTitleNew therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats Brain Res. 759 103–111 Occurrence Handle10.1016/S0006-8993(97)00251-5

    Article  Google Scholar 

  • Y. Kanemoto H. Nakase N. Akita T. Nakaki (2002) ArticleTitleEffects of anti-intercellular adhesion molecule-1 antibody on reperfusion injury induced by late reperfusion in the rat middle cerebral artery occlusion model Neurosurgery 51 1034–1042 Occurrence Handle10.1097/00006123-200210000-00033

    Article  Google Scholar 

  • L. A. Dawson S. Djali C. Gonzales M. A. Vinagra M. M. Zaleska (2000) ArticleTitleCharacterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate in spontaneously hypertensive rats Brain Res. Bull. 53(6) 767–776 Occurrence Handle10.1016/S0361-9230(00)00363-4

    Article  Google Scholar 

  • S. Shapira M. Sapir A. Wengier E. Grauer T. Kadar (2002) ArticleTitleAging has a complex effect on a rat model of ischemic stroke Brain Res. 925(2) 148–158 Occurrence Handle10.1016/S0006-8993(01)03270-X

    Article  Google Scholar 

  • Z. He S. Ibayashi H. Sugimori K. Fujii S. Sadoshima M. Fujishima (1997) ArticleTitleAge-related ischemia in the brain following bilateral carotid artery occlusion–collateral blood flow and brain metabolism Neurochem. Res. 22(1) 37–42 Occurrence Handle10.1023/A:1027321203294

    Article  Google Scholar 

  • A. P. Fotheringham C. A. Davies I. Davies (2000) ArticleTitleOedema and glial cell involvement in the aged mouse brain after permanent focal ischaemia Neuropathol Appl. Neurobiol. 26(5) 412–423 Occurrence Handle10.1046/j.1365-2990.2000.00265.x

    Article  Google Scholar 

  • S. Iskelel H. Islekel G. Guner N. Ozdamar (1999) ArticleTitleAlterations in superoxide dismutase, glutathione peroxidase and catalase activities in experimental cerebral ischemia–reperfusion Res. Exp. Med. 199 167–176 Occurrence Handle10.1007/s004330050121

    Article  Google Scholar 

  • T. Sugawara N. Noshita A. Lewen Y. Gasche M. Ferrand-Drake M. Fujimura Y. Morita-Fujimura P. H. Chan (2002) ArticleTitleOverexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation J. Neurosci. 22 209–217

    Google Scholar 

  • B. Onteniente C. Couriaud J. Braudeau A. Benchoua C. Guegan (2003) ArticleTitleThe mechanism of cell death in focal cerebral ischemia highlight neuroprotective perspectives by anti-caspase therapy Biochem. Pharmacol. 66 1643–1649 Occurrence Handle10.1016/S0006-2952(03)00538-0

    Article  Google Scholar 

  • N. Plesnila C. Zhu C. Culmsee M. Groger M. A. Moskowitz K. Blomgren (2004) ArticleTitleNuclear translocation of apoptosis-inducing factor after focal cerebral ischemia J. Cereb. Blood Flow Metab. 24 458–466 Occurrence Handle10.1097/00004647-200404000-00011

    Article  Google Scholar 

  • R.C. Li B.W. Row E. Gozal L. Kheirandish Q. Fan K.R. Brittian S.Z. Guo L.R. Sachleben SuffixJr. D. Gozal (2003) ArticleTitleCyclooxygenase 2 and intermittent hypoxia-induced spatial deficits in the rat Am J. Resp. Crit. Care Med. 168 469–475 Occurrence Handle10.1164/rccm.200211-1264OC

    Article  Google Scholar 

  • S. Tuzgen N. Tanriover M. Uzan E. Tureci T. Tanriverdi K. Gumustas (2003) ArticleTitleNitric oxide levels in rat cortex, hippocampus, cerebellum, and brainstem after impact accelaration head injury Neurol. Res. 25(1) 31–34 Occurrence Handle10.1179/016164103101201085

    Article  Google Scholar 

  • M. Suzuki M. Tabuchi M. Ikeda T. Tomita (2002) ArticleTitleConcurrent formation of peroxynitrite with the expression of inducible nitric oxide synthase in the brain during middle cerebral artery occlusion and reperfusion in rats Brain Res. 951(1) 113–120 Occurrence Handle10.1016/S0006-8993(02)03145-1

    Article  Google Scholar 

  • H. Mizushima C. J. Zhou K. Dohi R. Horai M. Asano Y. Iwakura T. Hirabayashi S. Arata S. Nakajo A. Takaki H. Ohtaki S. Shioda (2002) ArticleTitleReduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1 J. Comp. Neurol. 448 203–216 Occurrence Handle10.1002/cne.10262

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

    Rita I. M. Galvão, João P. L. Diógenes, Graziela C. L. Maia, Emídio A. S. Filho, Silvânia M. M. Vasconcelos, Geanne M. A. Cunha & Glauce S. B. Viana

  2. Department of Pathology and Legal Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

    Dalgimar B. de Menezes

  3. Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Rua Coronel Nunes de Melo, 1127, Fortaleza, Brazil, CEP 60430-270

    Glauce S. B. Viana

Authors
  1. Rita I. M. Galvão
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. João P. L. Diógenes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graziela C. L. Maia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emídio A. S. Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvânia M. M. Vasconcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dalgimar B. de Menezes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Geanne M. A. Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Glauce S. B. Viana
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galvão, R.I.M., Diógenes, J.P.L., Maia, G.C.L. et al. Tenoxicam Exerts a Neuroprotective Action after Cerebral Ischemia in Rats. Neurochem Res 30, 39–46 (2005). https://doi.org/10.1007/s11064-004-9684-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-004-9684-5

Keywords

Search

Navigation