Selective vulnerability to kainate-induced oxidative damage in different rat brain regions

Candelario-Jalil, Eduardo and Al-Dalain, Saied M. and Castillo, Ruben and Martinez, Gregorio and Leon, Olga S. (2001) Selective vulnerability to kainate-induced oxidative damage in different rat brain regions. [Journal (Paginated)]

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Some markers of oxidative injury were measured in different rat brain areas (hippocampus, cerebral cortex, striatum, hypothalamus, amygdala/piriform cortex and cerebellum) after the systemic administration of an excitotoxic dose of kainic acid (KA, 9 mg kg(-1) i.p.) at two different sampling times (24 and 48 h). Kainic acid was able to lower markedly (P < 0.05) the glutathione (GSH) levels in hippocampus, cerebellum and amygdala/piriform cortex (maximal reduction at 24 h). In a similar way, lipid peroxidation, as assessed by malonaldehyde and 4-hydroxyalkenal levels, significantly increased (P < 0.05) in hippocampus, cerebellum and amygdala/piriform cortex mainly at 24 h after KA. In addition, hippocampal superoxide dismutase (SOD) activity decreased significantly (P < 0.05) with respect to basal levels by 24 h after KA application. On the other hand, brain areas such as hypothalamus, striatum and cerebral cortex seem to be less susceptible to KA excitotoxicity. According to these findings, the pattern of oxidative injury induced by systemically administered KA seems to be highly region-specific. Further, our results have shown that a lower antioxidant status (GSH and SOD) seems not to play an important role in the selective vulnerability of certain brain regions because it correlates poorly with increases in markers of oxidative damage.

Item Type:Journal (Paginated)
Keywords:Excitotoxicity, kainic acid, oxidative damage, free radicals, brain, rat, oxidative stress, glutamate, neurodegeneration
Subjects:Neuroscience > Neurochemistry
ID Code:5667
Deposited By: Candelario-Jalil, Dr Eduardo
Deposited On:20 Aug 2007
Last Modified:11 Mar 2011 08:56

References in Article

Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.

1. D. W. Choi, Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623-634 (1988).

2. R. L. Macdonald and M. Stoodley, Pathophysiology of cerebral ischaemia. Neurol. Med. Chirurgica (Tokyo) 38, 1-11 (1998).

3. Y. Ben Ari, Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14, 375-403 (1985).

4. J. A. Dykens, A. Stern and E. Trenkner, Mechanisms of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J. Neurochem. 49, 1222-1228 (1987).

5. G. Sperk, H. Lassmann, H. Baran, F. Seitelberger and O. Hornykiewicz, Kainic acid-induced seizures: dose-relationship of behavioural, neurochemical and histopathological changes. Brain Res. 338, 289-295 (1985).

6. D. G. MacGregor, M. J. Higgins, D. I. Graham and T. W. Stone, Ascorbate attenuates the systemic kainate-induced neurotoxicity in the rat hippocampus. Brain Res. 727, 133-134 (1996).

7. J. W. Ferkany, R. Zaczek and J. T. Coyle, Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298, 757-759 (1982).

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

9. M. Tymianski and C. H. Tator, Abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery 38, 1176-1195 (1996).

10. Y. Cheng and A. Y. Sun, Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons. Neurochem. Res. 19, 1557-1564 (1994).

11. B. K. Siesjö, Pathophysiology and treatment of focal cerebral ischaemia. Part II. Mechanisms of damage and treatment. J. Neurosurg. 77, 337-354 (1992).

12. S. Orrenius, M. J. Burkitt, G. E. Kass, J. M. Dypbukt and P. Nicotera, Calcium ions and oxidative cell injury. Annals Neurol. 32 (Suppl.), S33-S42 (1992).

13. S. G. Carriedo, H. Z. Yin, S. L. Sensi and J. H. Weiss, Rapid Ca2+ entry through Ca2+-permeable AMPA/kainate channels triggers marked intracellular Ca2+ rises and consequent oxygen radical production. J. Neurosci. 18, 7727-7738 (1998).

14. A. Y. Sun, Y. Cheng, Q. Bu and F. Oldfield, The biochemical mechanism of the excitotoxicity of kainic acid. Mol. Chem. Neuropathol. 17, 51-63 (1992).

15. M. Floreani, S. D. Skaper, L. Facci, M. Lipartiti and P. Giusti, Melatonin maintains glutathione homeostasis in kainic acid-exposed rat brain tissues. FASEB J. 11, 1309-1315 (1997).

16. H. Baran, R. Heldt and G. Hertting, Increased prostaglandin formation in rat brain following systemic application of kainic acid. Brain Res. 404, 107-112 (1987).

17. H. Baran, K. Vass, H. Lassmann and O. Hornykiewicz, The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity. Brain Res. 646, 201-206 (1994).

18. E. Candelario-Jalil, H. H. Ajamieh, S. Sam, G. Martinez and O. S. León, Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur. J. Pharmacol. 390, 295-298 (2000).

19. O. Sanz, A. Estrada, I. Ferrer and A. M. Planas, Differential cellular distribution and dynamics of HSP70, cyclooxygenase-2 and c-FOS in the rat brain after transient focal ischaemia or kainic acid. Neuroscience 80, 221-232 (1997).

20. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates. Academic Press, New York (1986).

21. E. D. Hall, P. K. Andrus, J. S. Althaus and P. F. VonVoigtlander, Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain. J. Neurosci. Res. 34, 107-112 (1993).

22. I. Erdelmeier, D. Gerard-Monnier, J. C. Yadan and J. Chaudiere, Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem. Res. Toxicol. 11, 1184-1194 (1998).

23. G. Ellman and H. Lysko, A precise method for the determination of whole-blood and plasma sulfhydryl groups. Anal. Biochem. 93, 98-101 (1976).

24. G. S. Shukla, T. Hussain and S. V. Chandra, 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 (1987).

25. M. M. Bradford, 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 (1976).

26. P. Gass, P. Prior and M. Kiessling, Correlation between seizure intensity and stress protein expression after limbic epilepsy in the rat brain. Neuroscience 65, 27-36 (1995).

27. X. Zhang, D. L. Gelowitz, C. T. Lai, A. A. Boulton and P. H. Yu, Gradation of kainic acid –induced rat limbic seizures and expression of hippocampal heat shock protein-70. Eur. J. Neurosci. 9, 760-769 (1997).

28. K. Hashimoto, K. Watanabe, T. Nishimura, M. Iyo, Y. Shirayama and Y. Minabe, Behavioral changes and expression of heat shock protein hsp-70 mRNA, brain-derived neurotrophic factor mRNA, and cyclooxygenase-2 mRNA in rat brain following seizures induced by systemic administration of kainic acid. Brain Res. 804, 212-223 (1998).

29. G. Sperk, Kainic acid seizures in the rat. Prog. Neurobiol. 42, 1-32 (1994).

30. B. Halliwell and J. M. C. Gutteridge, Oxygen radicals and the nervous system. Trends Neurosci. 8, 22-29 (1985).

31. N. Dutrait, M. Culcasi, C. Cazevieille, S. Pietri and A. Müller, Calcium-dependent free radical generation in cultured retinal neurons injured by kainate. Neurosci. Lett. 198, 13-16 (1995).

32. A. J. Bruce and M. Baudry, Oxygen free radicals in rat limbic structures after kainate-induced seizures. Free Rad. Biol. Med. 18, 993-1002 (1995).

33. R. Chittajallu, S. P. Braithwaite, V. R. J. Clarke and J. M. Henley, Kainate receptors: subunits, synaptic localization and function. Trend Pharmacol Sci 20, 26-35 (1999).

34. D. T. Monoghan and C. W. Cotman, Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J. Neurosci. 5, 2909-2919 (1985).

35. H. J. Kim and J. S. Kwon, Effects of placing micro-implants of melatonin in striatum on oxidative stress and neuronal damage mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Arch. Pharm. Res. 22, 35-43 (1999).

36. L. Marklund, Properties of extracellular superoxide dismutase from human lung. Biochem. J. 220, 269-272 (1984).

37. K. Dobashi, K. Pahan, A. Chahal and I. Singh, Modulation of endogenous antioxidant enzymes by nitric oxide in rat C6 glial cells. J. Neurochem. 68, 1896-1903 (1997).

38. J. Huang and M. A. Philbert, Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis. Brain Res. 711, 184-192 (1996).


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