Abstract
Kainic acid (KA) administered systemically to rats produces seizures and brain damage. We measured an increase in reactive oxidant species (ROS) during KA-induced seizures in the extracellular fluid (ECF) of the piriform cortex, a brain region known to be subsequently damaged. Intracerebral microdialysis samples were collected and assayed for isoluminol-dependent chemiluminescence before and after injection of KA (16 mg/kg, ip). Hydrogen peroxide (H2O2) concentrations were calculated from catalase-sensitive chemiluminescence, the difference between total and catalase-resistant chemiluminescence. During generalized tonic-clonic seizures, both total and catalase-resistant chemiluminescence increased significantly in samples from brain ECF. Catalase-resistant chemiluminescence, most likely produced by ascorbic acid, increased for a full hour during sustained seizure activity. H2O2 concentrations showed a trend towards elevation during seizures. Increased ROS suggest that oxidative stress occurs in brain ECF during sustained seizure activity.
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Abbreviations
- ECF:
-
extracellular fluid
- H2O2 :
-
Hydrogen peroxide
- KA:
-
kainic acid
- KRB:
-
Kreb’s Ringer Bicarbonate
- NMDA:
-
N-methyl-d-aspartate
- RLU:
-
relative light units
- ROS:
-
reactive oxidant species
References
Bruce A. J. and Baudry M. (1995) Oxygen free radicals in rat limbic structures after kainate-induced seizures. Free Radical Biol. Med. 18, 993–1002.
Davison A. J., Kettle A. J., and Fatur D. J. (1986) Mechanism of the inhibition of catalase by ascorbate. J. Biol. Chem. 261, 1193–1200.
Emerson M. R., Samson F. E., and Pazdernik T. L. (1996) Evidence for an ascorbic acidcopperperoxide complex in lipid peroxidation. Soc. Neurosci. 22, 562.3.
Kojima H., Kikuchi K., Hirobe M., and Nagano T. (1997) Real-time measurement of nitric oxide production in rat brain by the combination of luminol-H2O2 chemiluminescence and microdialysis. Neurosci. Lett. 233, 157–159.
Layton M. E., Wagner J. K., Samson F. E., and Pazdernik T. L. (1997a) Redox changes in perfusates following intracerebral penetration of microdialysis probes. Neurochem. Res. 22, 735–741.
Layton M. E., Pazdernik T. L., and Samson F. E. (1997b) Cerebral penetration injury leads to hydrogen peroxide generation in microdialysis samples. Neurosci. Lett. 236, 1–4.
Layton M. E., Pazdernik T. L., and Samson F. E. (1998) KA causes redox changes in cerebral cortex extracellular fluid: NMDA receptor activity increases ascorbic acid whereas seizure activity increases uric acid. Neuropharmacology 37, 149–157.
Majewska M. D., Bell J. A., and London E. D. (1990) Regulation of the NMDA receptor by redox phenomena: inhibitory role of ascorbate. Brain Res. 537, 328–332.
McCord J. M., and Fridovich I. (1968) The reduction of cytochrome c by milk xanthine oxidase. J. Biol. Chem. 213, 5753–5760.
Miller D. M., and Aust S. D. (1989) Studies of ascorbate-dependent, iron-catalyzed lipid peroxidation. Arch. Biochem. Biophys. 271, 113–119.
Oliver C. N., Starke-Reed P., Stadtman E. R., Liu G. J., Carney J. M., and Floyd R. A. (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc. Natl. Acad. Sci. USA 87, 5144–5147.
Paschen W. (1992) Polyamine metabolism in different pathological states of the brain. Mol Chem. Neuropathol. 16, 241–271.
Paxinos G. and Watson C. (1986) The Rat Brain in Stereotaxic Coordinates. Academic, North Ryde, New South Wales, Australia, p. 25.
Pazdernik T. L., Layton M. E., Nelson S. R., and Samson F. E. (1992) The osmotic/calcium stress theory of brain damage: Are free radicals involved? Neurochem. Res. 17, 11–21.
Pedersen J. Z., Bernardi G., Centonze D., Pisani A., Rossi L., Rotilio G., et al. (1998) Hypoglycemia, hypoxia, and ischemia in a corticostriatal slice preparation: electrophysiologic changes and ascorbyl radical formation. J. Cereb. Blood Flow Metab. 18, 868–875.
Prat A. G. and Turrens J. F. (1990) Ascorbate- and hemoglobin-dependent brain chemiluminescence. Free Radical. Biol. Med. 8, 319–325.
Siesjo B. K., Agardh C. D., and Bengtsson F. (1989) Free radicals and brain damage. Cerebrovasc. Brain Metab. Rev. 1, 165–211.
Wade J. V., Samson F. E., Nelson S. R., and Pazdernik T. L. (1987) Changes in extracellular amino acids during soman- and KA-induced seizures. J. Neurochem. 49, 645–650.
Walker M. C., Galley P. T., Errington M. L., Shorvon S. D., and Jefferys J. G. (1995) Ascorbate and glutamate release in the rat hippocampus after perforant path stimulation: a “dialysis electrode” study. J. Neurochem. 65, 725–731.
Zucker D. K., Wooten G. F., and Lothman E. W. (1983) Blood-brain barrier changes with KA-induced limbic seizures. Exp. Neurol. 79, 422–433.
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Layton, M.E., Pazdernik, T.L. Reactive oxidant species in piriform cortex extracellular fluid during seizures induced by systemic kainic acid in rats. J Mol Neurosci 13, 63–68 (1999). https://doi.org/10.1385/JMN:13:1-2:63
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DOI: https://doi.org/10.1385/JMN:13:1-2:63