Epilepsy Research
Volume 30, Issue 2 , Pages 133-151 , April 1998

Anoxia during kainate status epilepticus shortens behavioral convulsions but generates hippocampal neuron loss and supragranular mossy fiber sprouting

  • Gary W Mathern

      Affiliations

    • Division of Neurosurgery, Reed Neurological Research Center, UCLA Medical Center, Los Angeles, CA 90095-1769, USA
    • The Brain Research Institute, The University of California, Los Angeles, CA, USA
    • The Mental Retardation Research Center, The University of California, Los Angeles, CA, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 310 2068777; fax: +1 310 2068461; e-mail: gmathern@ucla.edu
  • ,
  • Greg Price

      Affiliations

    • Department of Neurology, The University of California, Los Angeles, CA, USA
  • ,
  • Carlos Rosales

      Affiliations

    • Department of Neurology, The University of California, Los Angeles, CA, USA
    • The Brain Research Institute, The University of California, Los Angeles, CA, USA
  • ,
  • James K Pretorius

      Affiliations

    • The Brain Research Institute, The University of California, Los Angeles, CA, USA
  • ,
  • Alana Lozada

      Affiliations

    • The Brain Research Institute, The University of California, Los Angeles, CA, USA
  • ,
  • Delia Mendoza

      Affiliations

    • The Brain Research Institute, The University of California, Los Angeles, CA, USA

Received 9 January 1997 ,Revised 13 November 1997 ,Accepted 4 December 1997.

References 

  1. Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia. 1979;20:729–737
  2. Babb, T.L., Lieb, J.P., Brown, W.J., Pretorius, J., Crandall, P.H., 1984a. Distribution of pyramidal cell density and hyperexcitability in the epileptic human hippocampus. Epilepsia 25, 721–728.
  3. Babb, T.L., Brown, W.J., Pretorius, J., Davenport, C., Lieb, J.P., Crandall, P.H., 1984b. Temporal lobe volumetric cell densities in temporal lobe epilepsy. Epilepsia 25, 729–740.
  4. Babb, T.L., Brown, W.J., 1987. Pathological findings in epilepsy. In: Engel, J., Jr., editor. Surgical Treatment of the Epilepsies. Raven Press, New York, pp. 511–540.
  5. Babb TL, Pretorius JK, Kupfer WR, Crandall PH. Glutamate decarboxylase immunoreactive neurons are preserved in human epileptic hippocampus. J. Neurosci. 1989;9:2562–2574
  6. Babb TL, Kupfer WR, Pretorius JK, Crandall PH, Levesque MF. Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience. 1991;42:351–363
  7. Balestrino M. Pathophysiology of anoxic depolarization: new findings and a working hypothesis. J. Neurosci. Meth. 1995;59:99–103
  8. Ben-Ari, Y., 1981. Epilepsy: Changes in local glucose consumption and brain pathology produced by kainic acid. In: DiChiara, G., Gessa, G.L., (Eds.), Glutamate as a Neurotransmitter. Raven Press, New York, pp. 385–394.
  9. Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience. 1985;14:375–403
  10. Ben-Ari Y. Effects of anoxia and aglycemia on the adult and immature hippocampus. Biol. Neonate. 1992;62:225–230
  11. Ben-Ari Y, Tremblay E, Ottersen OP, Meldrum BS. The role of epileptic activity in hippocampal and `remote' cerebral lesions induced by kainic acid. Brain Res. 1980;191:79–97
  12. Berg-Johnsen J, Grøndahl TØ, Langmoen IA, Haugstad TS, Hegstad E. Changes in amino acid release and membrane potential during cerebral hypoxia and glucose deprivation. Neurol. Res. 1995;17:201–208
  13. Bertram EH, Cornett JF. The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures. Brain Res. 1993;625:295–300
  14. Bertram EH, Lothman EW. Morphometric effects of intermittent kindled seizures and limbic status epilepticus in the dentate gyrus of the rat. Brain Res. 1993;603:25–31
  15. Bertram EH, Lothman EW, Lenn NJ. The hippocampus in experimental chronic epilepsy: a morphometric analysis. Ann. Neurol. 1990;27:43–48
  16. Blennow G, Brierley JB, Meldrum BS, Siesjö BK. Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain. 1978;101:687–700
  17. Borgström L, Chapman AG, Siesjö BK. Glucose consumption in the cerebral cortex of rat during bicuculline-induced status epilepticus. J. Neurochem. 1976;27:971–973
  18. Bruton, C.J., 1988. The Neuropathology of Temporal Lobe Epilepsy. Oxford University Press, London.
  19. Camfield P, Camfield C, Gordon K, Dooley J. What types of epilepsy are preceded by febrile seizures? A population-based study of children. Dev. Med. Child Neurol. 1994;36:887–892
  20. Cataltepe O, Vannucci RC, Heitjan DF, Towfighi J. Effect of status epilepticus on hypoxic-ischemic brain damage in the immature rat. Pediatr. Res. 1995;38:251–257
  21. Cavazos JE, Golarai G, Sutula TP. Septotemporal variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats. Hippocampus. 1992;2:363–372
  22. Cavazzuti GB, Ferrari P, Lalla M. Follow-up study of 482 cases with convulsive disorders in the first year of life. Med. Child Neurol. 1984;26:425–437
  23. Chapman AG, Meldrum BS, Siesjö BK. Cerebral metabolic changes during prolonged epileptic seizures in rats. J. Neurochem. 1977;28:1025–1035
  24. Choi, D.W., 1991. Excitotoxicity. In: Meldrum, B.S. (Ed.), Excitatory Amino Acid Antagonists. Blackwell, Oxford, pp. 216–236.
  25. Corsellis, J.A.N., Bruton, C.J., 1983. Neuropathology of status epilepticus in humans. In: Delgado-Escueta, A.V., Wasterlain, C.G., Treiman, D.M., Porter, R.J. (Eds.), Status Epilepticus: Mechanisms of Brain Damage and Treatment, Advances in Neurology, vol. 34. Raven Press, New York, pp. 129–139.
  26. Cronin J, Dudek FE. Chronic seizures and collateral sprouting of dentate mossy fibers after kainic acid treatment in rats. Brain Res. 1988;474:181–184
  27. DeGiorgio CM, Tomiyasu U, Gott PS, Treiman DM. Hippocampal pyramidal cell loss in human status epilepticus. Epilepsia. 1992;33:23–27
  28. Dubinsky JM, Kristal BS, Elizondo-Fournier M. An obligate role for oxygen in the early stages of glutamate-induced, delayed neuronal death. J. Neurosci. 1995;15:7071–7078
  29. Duffy TE, Nelson SR, Lowry OH. Cerebral carbohydrate metabolism during acute hypoxia and recovery. J. Neurochem. 1972;19:959–977
  30. Fowler M. Brain damage after febrile convulsions. Arch. Dis. Child. 1957;32:67–76
  31. Franck, J.E., 1993. Cell death, plasticity and epilepsy: insights provided by experimental models of hippocampal sclerosis. In: Schwartzkroin, P.A. (Ed.), Epilepsy: Models, Mechanisms and Concepts. Cambridge University Press, Cambridge, pp. 281–303.
  32. Franck JE, Roberts DL. Combined kainate and ischemia produces `mesial temporal sclerosis'. Neurosci. Lett. 1990;118:159–163
  33. Fujikawa D. The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus. Brain Res. 1996;725:11–22
  34. Handforth A, Treiman DM. Functional mapping of the late stages of status epilepticus in the lithium-pilocarpine model in rat: a 14C-2-deoxyglucose study. Neuroscience. 1995;64:1075–1089
  35. Horton RW, Meldrum BS, Pedley TA, McWilliam JR. Regional cerebral blood flow in the rat during prolonged seizure activity. Brain Res. 1980;192:399–412
  36. Jenkins LW, Moszynski K, Lyeth BG, Lewelt W, DeWitt DS, Allen A, et al. Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res. 1989;477:211–224
  37. Leite JP, Bortolotto ZA, Cavalheiro EA. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci. Biobehav. Rev. 1990;14:511–517
  38. Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Yeoman KM, Mathern GW. Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainic acid in developing rats. Epilepsy Res. 1996;26:219–231
  39. Lemos T, Cavalheiro EA. Suppression of pilocarpine-induced status epileticus and the late development of epilepsy in rats. Exp. Brain Res. 1995;102:423–428
  40. Lorente de Nó R. Studies on the structure of the cerebral cortex. II. Continuation of the study of the ammonic system. J. Psychol. Neurol. 1934;45:113–177
  41. Lothman EW, Collins RC. Kainic acid induced seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates. Brain Res. 1981;218:299–318
  42. Lothman EW, Bertram EH, Kapur J, Stringer JL. Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus. Epilepsy Res. 1993;6:110–118
  43. Lundgren J, Smith M-L, Blennow G, Siesjö BK. Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage. Exp. Brain Res. 1994;99:43–55
  44. Magloczky Z, Freund TF. Delayed cell death in the contralateral hippocampus following kainate injection into the CA3 subfield. Neuroscience. 1995;66:847–860
  45. Masukawa LM, O'Connor WM, Lynott J, Burdette LJ, Uruno K, McGonigle P, et al. Longitudinal variation in cell density and mossy fiber reorganization in the dentate gyrus from temporal lobe epileptic patients. Brain Res. 1995;678:65–75
  46. Mathern, G.W., 1998. Hippocampal pathophysiology in experimental models. In: Kotagal, P., Lüders, H. (Eds.), The Epilepsies: Etiologies and Prevention. Academic Press, New York, in press.
  47. Mathern GW, Kupfer WR, Pretorius JK, Babb TL, Levesque MF. Onset and patterns of hippocampal sprouting in the rat kainate seizure model: evidence for progressive cell loss and neoinnervation in regio inferior and superior. Dendron. 1992;1:69–84
  48. Mathern GW, Cifuentes F, Leite JP, Pretorius JK, Babb TL. Hippocampal EEG excitability and chronic spontaneous seizures are associated with aberrant synaptic reorganization in the rat intrahippocampal kainate model. Electroencephalogr. Clin. Neurophysiol. 1993;87:326–339
  49. Mathern, G.W., Leite, J.P., Pretorius, J.K., Quinn, B., Peacock, W.J., Babb, T.L., 1994a. Children with severe epilepsy: evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation. Dev. Brain Res. 78, 70–80.
  50. Mathern, G.W., Babb, T.L., Vickrey, B.G., Melendez, M., Pretorius, J.K., 1994b. Traumatic compared to non-traumatic clinical-pathologic associations in temporal lobe epilepsy. Epilepsy Res. 19, 129–139.
  51. Mathern, G.W., Pretorius, J.K., Babb, T.L., 1995a. Quantified patterns of mossy fiber sprouting and neuron densities in hippocampal and lesional seizures. J. Neurosurg. 82, 211–219.
  52. Mathern, G.W., Pretorius, J.K., Babb, T.L., 1995b. Influence of the type of initial precipitating injury and at what age it occurs on course and outcome in patients with temporal lobe seizures. J. Neurosurg. 82, 220–227.
  53. Mathern, G.W., Babb, T.L., Vickrey, B.G., Melendez, M., Pretorius, J.K., 1995c. The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. Brain 118, 105–113.
  54. Mathern, G.W., Babb, T.L., Pretorius, J.K., Leite, J.P., 1995d. Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. J. Neurosci. 15, 3990–4004.
  55. Mathern, G.W., Babb, T.L., Pretorius, J.K., Melendez, M., Lévesque, M.F., 1995e. The pathophysiologic relationships between lesion pathology, intracranial ictal EEG onsets, and hippocampal neuron losses in temporal lobe epilepsy. Epilepsy Res. 21, 133–147.
  56. Mathern, G.W., Leite, J.P., Babb, T.L., Pretorius, J.K., Kuhlman, P.A., Mendoza, D., Sakamoto, A.C., Assirati, J.A., Adelson, P.D., Peacock, W.J., 1996a. Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining. NeuroReport 7, 1029–1035.
  57. Mathern, G.W., Babb, T.L., Mischel, P.S., Vinters, H.V., Pretorius, J.K., Leite, J.P., Peacock, W.J., 1996b. Childhood generalized and mesial temporal epilepsies demonstrate different amounts and patterns of hippocampal neuron loss and mossy fibre synaptic reorganization. Brain 119, 965–987.
  58. Mathern, G.W., Babb, T.L., Armstrong, D.L., 1997. Hippocampal sclerosis. In: Engel, J., Jr., Pedley, T.A. (Eds.), Epilepsy: A Comprehensive Textbook. Lippincott-Raven, New York, pp. 133–155.
  59. McNamara JO. Cellular and molecular basis of epilepsy. J. Neurosci. 1994;14:3413–3425
  60. Meldrum, B.S., 1975. Present views on hippocampal sclerosis and epilepsy. In: Williams, D. (Ed.), Modern Trends in Neurology. Butterworths, London, pp. 223–239.
  61. Meldrum, B.S., 1976. Secondary pathology of febrile and experimental convulsions. In: Brazier, M.A.B., Coceani, F. (Eds.), Brain Dysfunction in Infantile Febrile Convulsions. Raven Press, New York, pp. 213–222.
  62. Meldrum, B.S., 1983. Metabolic factors during prolonged seizures and their relation to nerve cell death. In: Delgado-Escueta, A.V., Wasterlain, C.G., Treiman, D.M., Porter, R.J. (Eds.), Advances in Neurology, vol. 34, Status Epilepticus. Raven Press, New York, pp. 261–275.
  63. Meldrum BS. The role of glutamate in epilepsy and other CNS disorders. Neurology. 1994;44(8):S14–S23
  64. Meldrum BS, Brierley JB. Prolonged epileptic seizures in primates: ischaemic cell change and its relation to ictal physiological events. Arch. Neurol. 1973;28:10–17
  65. Meldrum, B.S., Corsellis, J.A.N., 1984. Epilepsy. In: Adams, J.H., Corsellis, J.A.N., Duchen, L.W. (Eds.), Greenfield's Neuropathology. Wiley, New York, pp. 921–950.
  66. Meldrum BS, Horton RW. Physiology of status epilepticus in primates. Arch. Neurol. 1973;28:1–9
  67. Meldrum BS, Nilsson B. Cerebral blood flow and metabolic rate early and late in prolonged epileptic seizures induced in rats by bicuculline. Brain. 1976;99:523–542
  68. Meldrum BS, Horton RW, Brierley JB. Epileptic brain damage in adolescent baboons following seizures induced by allylglycine. Brain. 1974;97:407–418
  69. Mello LEAM, Cavalheiro EA, Tan AM, Kufper WR, Pretorius JK, Babb TL, et al. Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia. 1993;34:985–995
  70. Nadler JV, Cuthbertson GJ. Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res. 1980;195:47–56
  71. Nawashiro H, Shima K, Chigasaki H. Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat. Neurol. Res. 1995;17:455–460
  72. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N. Engl. J. Med. 1976;295:1029–1033
  73. Newell DW, Barth A, Papermaster V, Malouf AT. Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures. J. Neurosci. 1995;15:7702–7711
  74. Okazaki MM, Evenson DA, Nadler JV. Hippocampal mossy fiber sprouting and synapse formation after status epilepticus in rats: visualization after retrograde transport of biocytin. J. Comp. Neurol. 1995;352:515–534
  75. Penning DH, Goh JW, El-Beheiry H, Brien JF. Effect of hypoxia on glutamate efflux and synaptic transmission in the guinea pig hippocampus. Brain Res. 1993;620:301–304
  76. Pinard E, Tremblay E, Ben-Ari Y, Seylaz J. Blood flow compensates oxygen demand in the vulnerable CA3 region of the hippocampus during kainate-induced seizures. Neuroscience. 1984;13:1039–1049
  77. Pohle W, Rauca C. Hypoxia protects against the neurotoxicity of kainic acid. Brain Res. 1994;644:297–304
  78. Pollard H, Charriaut-Marlangue C, Cantagrel S, Represa A, Robain O, Moreau J, et al. Kainate-induced apoptotic cell death in hippocampal neurons. Neuroscience. 1994;63:7–18
  79. Scholz W. The contribution of patho-anatomical research to the problem of epilepsy. Epilepsia. 1959;1:36–55
  80. Schurr A, Payne RS, Heine MF, Rigor BM. Hypoxia, excitotoxicity, and neuroprotection in the hippocampal slice preparation. J. Neurosci. Meth. 1995;59:129–138
  81. Sloviter, R.S., 1989. Chemically defined hippocampal interneurons and their possible relationship to seizure mechanisms. In: Köhler, C., Chan-Palay, V. (Eds.), The Hippocampus: New Vistas. Liss, New York, pp. 443–461.
  82. Spielmeyer W. Die pathogenese des epileptischen krampfes. Z. Ges. Neurol. Psychiat. 1927;109:501–520
  83. Sundstrom LE, Mitchell J, Wheal HV. Bilateral reorganisation of mossy fibres in the rat hippocampus after a unilateral intracerebroventricular kainic acid injection. Brain Res. 1993;609:321–326
  84. Sutula T, Cavazos J, Golarai G. Alteration of long-lasting structural and functional effects of kainic acid in the hippocampus by brief treatment with phenobarbital. J. Neurosci. 1992;12:4173–4187
  85. Swan JH, Meldrum BS, Simon RP. Hyperglycemia does not augment neuronal damage in experimental staus epilepticus. Neurology. 1986;36:1351–1354
  86. Takata T, Okada Y. Effects of deprivation of oxygen or glucose on the neural activity in the guinea pig hippocampal slice: intracellular recording study of pyramidal neurons. Brain Res. 1995;683:109–116
  87. Tauck DL, Nadler JV. Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J. Neurosci. 1985;5:1016–1022
  88. Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L. Limbic seizures produced by pilocarpine in rats: behavioral, electroencephalographic and neuropathological study. Behav. Brain Res. 1983;9:315–335
  89. Vannucci, R.C., 1981. Metabolic and pathological consequences of experimental febrile seizures and status epilepticus. In: Nelson, K.B., Ellenberg, J.H. (Eds.), Febrile Seizures. Raven Press, New York, pp. 43–57.
  90. Verity CM, Ross EM, Golding J. Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study. Br. Med. J. 1993;307:225–228
  91. Wasterlain, C., Sankar, R., 1993. Excitoxity and the developing brain. In: Avanzini, G., Fariello, R., Heinemann, U., Mutani, R. (Eds.), Epileptogenic and Excitotoxic Mechanisms. Libbey, New York, pp. 135–151.
  92. Wasterlain CG, Fujikawa DG, Penix L, Sankar R. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia. 1993;34(1):S37–S53

PII: S0920-1211(97)00103-4

Epilepsy Research
Volume 30, Issue 2 , Pages 133-151 , April 1998