creators_name: Candelario-Jalil, Eduardo creators_name: Mhadu, Noel H. creators_name: Al-Dalain, Saied M. creators_name: Martinez, Gregorio creators_name: Leon, Olga S. type: journalp datestamp: 2007-08-20 lastmod: 2011-03-11 08:56:56 metadata_visibility: show title: Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils ispublished: pub subjects: neuro-chem full_text_status: public keywords: oxidative stress, cerebral ischemia, glutathione, lipid peroxidation, antioxidants, brain abstract: The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention. date: 2001-11 date_type: published publication: Neuroscience Research volume: 41 number: 3 publisher: Elsevier pagerange: 233-241 refereed: TRUE referencetext: 1. Anderson, M.E., 1985. Determination of glutathione and glutathione disulfide in biological samples. Meth. Enzymol. 113, 548-555. 2. Barker, J.E., Heales, S.J.R., Cassidy, A., Bolaños, J.P., Land, J.M., Clark, J.B., 1996. Depletion of brain glutathione results in a decrease of glutathione reductase activity; an enzyme susceptible to oxidative damage. Brain Res. 716, 118-122. 3. Bradford, M.M., 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal. Biochem. 72, 248-254. 4. Caldwell, M., O´Neill, M., Early, B., Kelly, J.P., Leonard, B.E., 1995. NG-nitro-L-arginine methyl ester protects against lipid peroxidation in the gerbil following cerebral ischemia. Eur. J. Pharmacol. 285, 203-206. 5. Caldwell, M., O´Neill, M., Early, B., Leonard, B.E., 1994. NG-nitro-L-arginine protects against ischaemia-induced increases in nitric oxide and hippocampal neuro-degeneration in the gerbil. Eur. J. Pharmacol. 260, 191-200. 6. Candelario-Jalil, E., Ajamieh, H.H., Sam, S., Martínez, G., León, O.S., 2000. Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur. J. Pharmacol. 390, 295-298. 7. Cao, W., Carney, J.M., Duchon, A., Floyd, R.A., Chevion, M., 1988. Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci. Lett. 88, 233-238. 8. Carlberg, I., Mannervik, B., 1985. Glutathione reductase. In: Colowick, S.P., Kaplan, N.O. (Eds.), Methods in Enzymology, vol. 113. Academic Press, Orlando, FL, pp. 484-490. 9. Chabrier, P.E., Auguet, M., Spinnewyn, B., Auvin, S., Cornet, S., Demerle-Pallardy, C., Guilmard-Favre, C., Marin, J.G., Pignol, B., Guillard-Roubert, V., Roussillot-Charnet, C., Schulz, J., Viossat, I., Bigg, D., Moncada, S., 1999. BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: a promising neuroprotective strategy. Proc Natl Acad Sci U S A 96, 10824-10829. 10. Chan, P.H., 1996. Role of oxidants in ischemic brain damage. Stroke 27, 1124-1129. 11. Chandra, J., Samali, A., Orrenius, S., 2000. Triggering and modulation of apoptosis by oxidative stress. Free Rad. Biol. Med. 29, 323-333. 12. Evans, P.H., 1993. Free radicals in brain metabolism and pathology. Br. Med. Bull. 49, 577-587. 13. Facchinetti, F., Dawson, V.L., Dawson, T.M., 1998. Free radicals as mediators of neuronal injury. Cell Mol. Neurobiol. 18, 667-682. 14. Flohé, L., Gunzler, W.A., 1984. Assays of glutathione peroxidase. In: Colowick, S.P., Kaplan, N.O. (Eds.), Methods in Enzymology, vol. 105. Academic Press, Orlando, FL, pp. 114-121. 15. Floreani, M., Skaper, S.D., Facci, L., Lipartiti, M., Giusti, P., 1997. Melatonin maintains glutathione homeostasis in kainic acid-exposed rat brain tissues. FASEB J. 11, 1309-1315. 16. Floyd, R.A., Carney, J.M., 1991. Age influence on oxidative events during brain ischemic/reperfusion. Arch. Gerontol. Geriatr. 12, 155-177. 17. Gay, C., Collins, J., Gebicki, J.M., 1999. Hydroperoxide assay with the ferric-xylenol orange complex. Anal. Biochem. 273, 149-155. 18. Globus, M.Y.T., Ginsberg, M.D., Dietrich, W.D., 1987. Substantia nigra lesion protects against ischemic damage in the striatum. Neurosci. Lett. 80, 251-256. 19. Haba, K., Ogawa, N., Mizukawa, K., Mori, A., 1991. Time course of changes in lipid peroxidation, pre- and postsynaptic cholinergic indices, NMDA receptor binding and neuronal death in the gerbil hippocampus following transient ischemia. Brain Res. 540, 116-122. 20. Hall, E.D., Andrus, P.K., Althaus, J.S., VonVoightlander, P.F., 1993. Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain. J. Neurosci. Res. 34, 107-112. 21. Hall, E.D., Oostveen, J.A., Andrus, P.K., Anderson, D.K., Thomas, C.E., 1997. Immunocytochemical method for investigating in vivo neuronal oxygen radical-induced lipid peroxidation. J. Neurosci. Meth. 76, 115-122. 22. Halliwell, B., Gutteridge, J.M.C., 1985. Oxygen radicals and the nervous system. Trends Neurosci. 8, 22-29. 23. Huang, J., Philbert, M.A., 1996. Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbations of subcellular glutathione homeostasis. Brain Res. 711, 184-192. 24. Kindy, M.A., Bhat, A.N., Bhat, N.R., 1992. Transient ischemia stimulates glial fibrillary acid protein and vimentine gene expression in the gerbil neocortex, striatum and hippocampus. Mol. Brain Res. 13, 199-206. 25. Kirino, T., 1982. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239, 57-69. 26. Kitagawa, K., Matsumoto, M., Oda, T., Niinobe, M., Hata, R., Handa, N., Fukunaga, R., Isaka, Y., Kimura, K., Maeda, H., 1990. Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death. Neuroscience 35, 551-558. 27. Lee, J.M., Zipfel, G.J., Choi, D.W., 1999. The changing landscape of ischaemic brain injury mechanisms. Nature (Suppl) 399, A7-A14. 28. Macdonald, R.L., Stoodley, M., 1998. Pathophysiology of cerebral ischemia. Neurol. Med. Chir. (Tokyo) 38, 1-11. 29. Martínez, G., Candelario-Jalil, E., Giuliani, A., León, O.S., Sam, S., Delgado, R., Nuñez-Sellés, A.J., 2001. Mangifera indica L. extract (QF808) reduces ischaemia-induced neuronal loss and oxidative damage in the gerbil brain. Free Radic. Res. In press. 30. Mattson, M.P., 1998. Modification of ion homeostasis by lipid peroxidation: roles in neuronal degeneration and adaptive plasticity. Trends Neurosci. 20, 53-57. 31. McIntosh, L.J., Hong, K.E., Sapolsky, R.M., 1998. Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies. Brain Res. 791, 209-214. 32. Melchiorri, D., Reiter, R.J., Chen, L.D., Sewerynek, E., Nisticó, G., 1996. Melatonin affords protection against kainate-induced in vitro lipid peroxidation in brain. Eur. J. Pharmacol. 305, 239-242. 33. Nitatori, T., Sato, N., Waguri, S., Karasawa, Y., Araki, H., Shibanai, K., Kominami, E., Uchiyama, Y., 1995. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J. Neurosci. 15, 1001-1011. 34. Ohtsuki, T., Kitagawa, K., Yanagihara, T., Matsumoto, M., 1996. Induction of cyclooxygenase-2 mRNA in gerbil hippocampal neurons after transient forebrain ischemia. Brain Res. 736, 353-356. 35. Oostveen, J.A., Dunn, E., Carter, D.B., Hall, E.D., 1998. Neuroprotective efficacy and mechanisms of novel pyrrolopyrimidine lipid peroxidation inhibitors in the gerbil forebrain ischemia model. J. Cereb. Blood Flow Metab. 18, 539-547. 36. Paxinos, G., Watson, C., 1998. The rat brain in stereotaxic coordinates. 4th Edition. Academic Press, New York. 37. Pigeolet, E., Remacle, J., 1991. Susceptibility of glutathione peroxidase to proteolysis after oxidative alterations by peroxides and hydroxyl radicals. Free Rad. Biol. Med. 11, 191-195. 38. Rao, V.L.R., Rao, A.M., Dogan, A., Bowen, K.K., Hatcher, J.F., Rothstein, J.D., Dempsey, R.J., 2000. Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia. Neurochem. Int. 36, 531-7. 39. Ren, Y., Li, X., Xu, Z.C., 1997. Asymmetrical protection of neostriatal neurons against transient forebrain ischemia by unilateral dopamine depletion. Exp. Neurol. 146, 250-257. 40. Sato, N., Iwata, S., Nakamura, K., Hori, T., Mori, K., Yodoi, J., 1995. Thiol-mediated redox regulation of apoptosis: possible roles of cellular thiols other than glutathione in T cell apoptosis. J. Immunol. 154, 3194-3203. 41. Schulz, J.B., Lindenau, J., Seyfried, J., Dichgans, J., 2000. Glutathione, oxidative stress and neurodegeneration. Eur. J. Biochem. 267, 4904-4911. 42. Shukla, G.S., Hussain, T., Chandra, S.V., 1987. Possible role of superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats. Life Sci. 14, 2215-2225. 43. Song, J.H., Shin, S.H., Ross, G.M., 1999. Prooxidant effects of ascorbate in rat brain slices. J. Neurosci. Res. 58, 328-336. 44. Springer, J.E., Azbill, R.D., Mark, R.J., Begley, J.G., Waeg, G., Mattson, M.P., 1997. 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. J. Neurochem. 68, 2469-2476. 45. Tietze, F., 1969. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal. Biochem. 27, 502-522. 46. Urabe, T., Yamasaki, Y., Hattori, N., Yoshikawa, M., Uchida, K., Mizuno, Y., 2000. Accumulation of 4-hydroxynonenal-modified proteins in hippocampal CA1 pyramidal neurons precedes delayed neuronal damage in the gerbil brain. Neuroscience 100, 241-50. 47. Wüllner, U., Seyfried, J., Groscurth, P., Beinroth, S., Winter, S., Gleichmann, M., Heneka, M., Löschmann, P.A., Schulz, J.B., Weller, M., Klockgether, T., 1999. Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function. Brain Res. 826, 53-62. 48. Yamaguchi, S., Ogata, H., Hamaguchi, S., Kitajima, T., 1998. Superoxide radical generation and histopathological changes in hippocampal CA1 after ischemia/reperfusion in gerbils. Can. J. Anaesth. 45, 226-232. 49. Yrjänheikki, J., Keinänen, R., Pellikka, M., Hökfelt, T., Koistinaho, J., 1998. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc. Natl. Acad. Sci. USA 95, 15769-15774. citation: Candelario-Jalil, Eduardo and Mhadu, Noel H. and Al-Dalain, Saied M. and Martinez, Gregorio and Leon, Olga S. (2001) Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils. [Journal (Paginated)] document_url: http://cogprints.org/5644/1/Neurosci_Res_2001_Candelario-Jalil_et_al.pdf