Kainic Acid Seizures and Neuronal Cell Death: Insights from Studies of Selective Lesions and Drugs

  • J. V. Nadler
  • M. M. Okazaki
  • M. Gruenthal
  • B. Ault
  • D. R. Armstrong
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 203)


Hippocampal pathology (Ammon’s horn sclerosis (AHS)) is a well-recognized finding in the brains of temporal lobe epileptics (Meldrum and Corsellis, 1984). Classical AHS involves extensive loss of neurons from hippocampal area CA1 (h1, Sommer sector), a less extensive neuronal deficit in the CA3-CA4 area (h3-h5, endblade, endfolium), and relative sparing of neurons in the h2 area (‘resistant zone’; area CA2 and the adjacent portion of area CA3a which contains the mossy fiber endbulb) and in the fascia dentata. Most commonly, some neuronal loss in other brain regions, particularly the amygdala, thalamus and cerebral neocortex, accompanies the hippocampal lesion. Although the near-total loss of neurons from area CA1 is the most striking feature of AHS in many patients, there is reason to believe that the most vulnerable neurons are the CA3 hippocampal pyramidal cells and the morphologically diverse neurons of area CA4 (Margerison and Corsellis, 1966).


Status Epilepticus Pyramidal Cell Temporal Lobe Epilepsy Mossy Fiber Kainic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ben-Ari, Y., Tremblay, E., Ottersen, O.P., and Meldrum, B.S., 1980, The role of epileptic activity in hippocampal and ‘remote’ cerebral lesions induced by kainic acid, Brain Res. 191: 79.Google Scholar
  2. Ben-Ari, Y., Tremblay, E., Riche, D., Ghilini, G., and Naquet, R., 1981, Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy, Neuroscience 7: 1361.Google Scholar
  3. Ben-Ari, Y., 1985, Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy, Neuroscience 14: 375.Google Scholar
  4. Berger, M., and Ben-Ari, Y., 1983, Autoradiographic visualization of [3H]kainic acid receptor subtypes in the rat hippocampus, Neurosci. Lett. 39:237.Google Scholar
  5. Chavkin, C., Bakhit, C., Weber, E., and Bloom, F.E., 1983, Relative contents and concomitant release of prodynorphin/neoendorphin-derived peptides in rat hippocampus, Proc. Natl. Acad. Sci. USA 80:7669.Google Scholar
  6. Clifford, D.B., Lothman, E.W., Dodson, W.E., and Ferrendelli, J.A., 1982, Effect of anticonvulsant drugs on kainic acid-induced epileptiform activity, ExD. Neurol. 76:156.Google Scholar
  7. Elliott, K.A.C., 1969, The use of brain slices, in: Handbook of Neurochemistry. Volume 2 A. Lajtha, ed., Plenum Press, New York, p. 103.Google Scholar
  8. Ferkany, J.W., and Coyle, J.T., 1983, Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids, J. Pharmacol. Exp. Ther. 225:399.Google Scholar
  9. Fisher, R.S., and Alger, B.E., 1984, Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice, J. Neurosci. 4:1312.Google Scholar
  10. Franck, J.E., and Schwartzkroin, P.A., 1985, Do kainate-lesioned hippocampi become epileptogenic?, Brain Res. 329: 309.Google Scholar
  11. Gruenthal, M., Ault, B., Armstrong, D.R., and Nadler, J.V., 1984, Baclofen blocks kainic acid-induced epileptiform activity, Soc. Neurosci. Abstr. 10:184.Google Scholar
  12. Heggli, D.E., and Malthe-S6renssen, D., 1982, Systemic injection of kainic acid: effect on neurotransmitter markers in piriform cortex, amygdaloid complex and hippocampus and protection by cortical lesioning and anti-convulsants, Neuroscience 7: 1257.Google Scholar
  13. Lancaster, B., and Wheal, H.V., 1984, Chronic failure of inhibition of the CA1 area of the hippocampus following kainic acid lesions of the CA3/4 area, Brain Res. 295: 317.Google Scholar
  14. Lassmann, H., Petsche, U., Kitz, K., Baran, H., Sperk, G., Seitelberger, F., and Hornykiewicz, 0., 1984, The role of brain edema in epileptic brain damage induced by systemic kainic acid injection, Neuroscience 13: 691.Google Scholar
  15. Lothman, E.W., and Collins, R.C., 1981, Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates, Brain Res. 218: 299.Google Scholar
  16. Margerison, J.H., and Corsellis, J.A.N., 1966, Epilepsy and the temporal lobes, Brain, 89:499.Google Scholar
  17. Meldrum, B.S., 1983, Metabolic factors during prolonged seizures and their relation to nerve cell death, in: Status Epilepticus: Mechanisms of Brain Damage and Treatment, Advances in Neurology, Volume 34 A.V. Delgado-Escueta, C.G. Wasterlain, D.M. Treiman, and R.J. Porter, eds., Raven Press, New York, p. 261.Google Scholar
  18. Meldrum, B.S., and Corsellis, J.A.N., 1984, Epilepsy, in: Greenfield’s Neuropathology J.H. Adams, J.A.N. Corsellis, and L.W. Duchen, eds., John Wiley and Sons, New York, p. 921.Google Scholar
  19. Menini, C., Meldrum, B.S., Riche, D., Silva-Comte, C., and Stutzmann, J.M., 1980, Sustained limbic seizures induced by intraamygdaloid kainic acid in the baboon: symptomatology and neuropathological consequences, Ann. Neurol. 8:501.Google Scholar
  20. Monaghan, D.T., and Cotman, C.W., 1982, The distribution of [3H]kainic acid binding sites in rat CNS as determined by autoradiography, Brain Res., 252: 91.PubMedCrossRefGoogle Scholar
  21. Nadler, J.V., and Cuthbertson, G.J., 1980, Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways, Brain Res. 195: 47.Google Scholar
  22. Nadler, J.V., 1981, Kainic acid as a tool for the study of temporal lobe epilepsy, Life Sqi. 29: 2031.Google Scholar
  23. Nadler, J.V., Evenson, D.A., and Smith, E.M., 1981, Evidence from lesion studies for epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation, Brain Res. 201: 405.Google Scholar
  24. Nadler, J.V., and Evenson, D.A., 1983, Use of excitatory amino acids to make axon-sparing lesions of hypothalamus, in: Hormone Action, Part H: Neuroendocrine Peptides, Methods in Enzymology, Volume 103 P.M. Conn, ed., Academic Press, New York, p. 393.Google Scholar
  25. Nevander, G., Ingvar, M., Auer, R., and Siesjö, B., 1984, Irreversible neuronal damage after short periods of status epilepticus, Acta Physiol. Scand. 120:155.Google Scholar
  26. Nitecka, L., Tremblay, E., Charton, G., Bouillot, J.P., Berger, M.L., and Ben-Ari, Y., 1984, Maturation of kainic acid seizure-brain damage syndrome in the rat. H. Histopathological sequelae, Neuroscience 13: 1073.Google Scholar
  27. Pastuszko, A., Wilson, D.F., and Erecinska, M., 1984, Effects of kainic acid in rat brain synaptosomes: the involvement of calcium, J. Neurochem., 43:747.Google Scholar
  28. Potashner, S.J., and Gerard, D., 1983, Kainate-enhanced release of D-[3H]- aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital, J. Neurochem. 40:1548.Google Scholar
  29. Racine, R.J., 1972, Modification of seizure activity by electrical stimulation. II. Motor seizure, Electroenceph. Clin. Neurophysiol. 32:281.Google Scholar
  30. Robinson, J.H., and Deadwyler, S.A., 1981, Kainic acid produces depolarization of CA3 pyramidal cells in the in vitro hippocampal slice, Brain Res., 221: 117.Google Scholar
  31. Sawada, S., and Yamamoto, C., 1984, Fast and slow depolarizing potentials induced by short pulses of kainic acid in hippocampal neurons, Brain Res., 324: 279.Google Scholar
  32. Shinozaki, H., and Konishi, S., 1970, Actions of several anthelmintics and insecticides on rat cortical neurones, Brain Res. 24: 368.Google Scholar
  33. Sloviter, R.S., 1983, Epileptic brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies, Brain Res. Bull. 10:675.Google Scholar
  34. Sommer, W., 1880, Erkrankungen des Ammonshorns als aetiologisches Moment der Epilepsie, Arch. Psychiatr. Nervenkrkh. 10:631.Google Scholar
  35. Sperk. G., Lassmann, H., Baran, H., Kish, S.J., Seitelberger, F., and Hornykiewicz, 0., 1983, Kainic acid induced seizures: neurochemical and histopathological changes, Neuroscience 10: 1301.Google Scholar
  36. Tauck, D.L., and Nadler, J.V., 1985, Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats, J. Neuro-sci., 5:1016.Google Scholar
  37. Unnerstall, J.R., and Wamsley, J.K., 1983, Autoradiographic localization of high-affinity [3H]kainic acid binding sites in the rat forebrain, Eur. J. Pharmacol. 86:361.Google Scholar
  38. Westbrook, G.L., and Lothman, E.W., 1983, Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity, Brain Res. 273:97.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • J. V. Nadler
    • 1
  • M. M. Okazaki
    • 1
  • M. Gruenthal
    • 1
  • B. Ault
    • 2
  • D. R. Armstrong
    • 1
  1. 1.Department of pharmacologyDuke University Medical CenterDurhamUSA
  2. 2.Department of PharmacologyBurroughs-Wellcome Co.USA

Personalised recommendations