Initiation, Propagation and Arrest of Seizures

  • D. M. Woodbury
  • J. W. Kemp


Ideally, the best model to study the mechanisms of seizures is man himself. However, other than EEG recordings, depth electrode studies and occasional biopsies of epileptogenic foci this is difficult to do. This is the case because detailed analysis of the basic neurophysiological and biochemical mechanisms of seizures involves work on the brain itself and sometimes removal of brain samples and this is not possible to do in humans. Consequently, experimental models of epilepsy must be used instead. The relevance of such studies is clearly related to the degree to which the experimental models approximate the disease in humans. The ideal model for studying the basic mechanisms of seizures is one that closely approximates human epilepsy and yet is readily available, inexpensive and easy to work with. No model at present meets all these criteria, but all models are potentially useful for studying at least one aspect of the mechanisms of seizures.


Glial Cell Carbonic Anhydrase Spike Activity Carbonic Anhydrase Activity Epileptogenic Focus 
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. 1.
    Aird, R.D., and Woodbury, D.M. (1974): The Management of Epilepsy. Charles C. Thomas, Springfield, Ill.Google Scholar
  2. 2.
    Ajmone-Marsan, C. (1969): Acute effects of topical epileptogenic agents. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope. Little, Brown and Co., Boston, 299–319.Google Scholar
  3. 3.
    Altman, J., and Das, G.D. (1964): Autoradiographic examination of the effects of enriched environment on the rate of glial multiplication in the adult brain. Nature, 204: 1161–1163.PubMedCrossRefGoogle Scholar
  4. 4.
    Ashcroft, G.W., Dow, R.C., Emson, P.C., Harris, P., Ingleby, J., Jospeh, M.H., and McQueen, J.K. (1974): A collaborative study of cobalt lesions in the rat as a model for epilepsy. In: Epilepsy. Proceedings of the Hans Berger Centenary Symposium, ed. P. Harris and C. Mawdsley, Churchill Livingstone, Edinburgh, 115–124Google Scholar
  5. 5.
    Ayala, G.F., Matsumoto, H., and Gumnit, R.J. (1970): Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J. Neurophysiol. 33: 73–85.PubMedGoogle Scholar
  6. 6.
    Bourke, R.S. (1969): Evidence for mediated transport of chloride in cat cortex in vitro. Exp. Brain Res. 8:219–231.Google Scholar
  7. 7.
    Bourke, R.S., and Nelson, K.M. (1972): Further studies on the K+-dependent swelling of primate cerebral cortex in vivo: The enzymatic basis of the K+-dependent transport of chloride. J. Neurochem. 19:663–685.PubMedCrossRefGoogle Scholar
  8. 8.
    Brizzee, K.R., Vogt, J. and Kharetchko, X. (1964): Postnatal changes in glia/neuron index with a comparison of methods of cell enumeration in white rat. Progr. Brain Res. 4: 136–149.CrossRefGoogle Scholar
  9. 9.
    Brown, W.J. (1973): Structural substrates of seizure foci in the human temporal lobe. In: Epilepsy: Its Phenomena in Man, edited by M.A.B. Brazier. Acad. Press, New York.Google Scholar
  10. 10.
    Cendella, R.J. and Craig, C.R. (1973): Changes in cerebral cortical lipids in cobalt-induced epilepsy. J. Neurochem. 21: 743–748.CrossRefGoogle Scholar
  11. 11.
    DeRobertis, E., Rodriquez de Lores, Arnaiz, G., and Alberici, M. (1969): Ultrastructural neurochemistry. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, 137–158. Little Brown and Co., Boston.Google Scholar
  12. 12.
    Diamond, M.C., Law, F., Rhodes, H., Lindner, B., Rosenzweig, M.R., Krech, D., and Bennett, E.L. (1966): Increases in cortical depth and glial numbers in rats subjected to enriched environment. J. Comp. Neurol. 128: 117–126.PubMedCrossRefGoogle Scholar
  13. 13.
    Dichter, M.A., Herman, C.J. and Selzer, M. (1972): silent cells during interictal discharges and seizures in hippocampal penicillin foci. Evidence for the role of extracellular K+ in the transition from the interictal state to seizures. Brain Res. 48: 173–183.PubMedCrossRefGoogle Scholar
  14. 14.
    Dow, R.C. (1965): Extrinsic regulatory mechanisms of seizure activity. Epilepsia 6: 122–140.PubMedCrossRefGoogle Scholar
  15. 15.
    Dropp, J.J. and Sodetz, F.J. (1971): Autoradiographic study of neurons and neuroglia in autonomic ganglia of behaviorally stressed rats. Brain Res. 33: 419–430.PubMedCrossRefGoogle Scholar
  16. 16.
    Escueta, A.V., and Appel, S.H. (1972): Brain synapses. An in vitro model for the study of seizures. Arch. Intern. Med. 129: 333–344.PubMedCrossRefGoogle Scholar
  17. 17.
    Esplin, D.W., and Zablocka-Esplin, B. (1969): Mechanisms of action of convulsants. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co., Boston, 167–183.Google Scholar
  18. 18.
    Fertiziger, A.P., and Ranck, J.B. (1970): Potassium accumulation in interictal space during epileptiform seizures. Exp. Neurol. 26: 571–585.Google Scholar
  19. 19.
    Giacobini, E. (1962): A cytochemical study of the localization of carbonic anhydrase in the nervous system. J. Neurochem. 9: 169–177.PubMedCrossRefGoogle Scholar
  20. 20.
    Gill, T.H., Young, O.M., and Tower, D.B. (1974): The uptake of 36Cl into astrocytes in tissue culture by potassium-dependent, saturable process. J. Neurochem. 23: 1011–1018.PubMedCrossRefGoogle Scholar
  21. 21.
    Glötzner, F.L. (1973): Membrane properties of neuroglia in epileptogenic gliosis. Brain Res., 55: 159–171.PubMedCrossRefGoogle Scholar
  22. 22.
    Goddard, G.V. (1967): Development of epileptic seizures through brain stimulation at low intensity. Nature 214: 1020–1021.PubMedCrossRefGoogle Scholar
  23. 23.
    Goddard, G.V., McIntyre, D.C., and Leech, C.K. (1969): A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. 25: 295–330.PubMedCrossRefGoogle Scholar
  24. 24.
    Goldensohn, E. (1969): Discussion. Experimental seizure mechanisms. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co., Boston, 289–298.Google Scholar
  25. 25.
    Grafstein, B. (1956): Mechanism of spreading cortical depression. J. Neurophysiol. 19: 154–171.PubMedGoogle Scholar
  26. 26.
    Gross, G.J., and Woodbury, D.M. (1972): Effects of pentylenetetrazol on ion transport in the isolated toad bladder. J. Pharmacol. Exp. Ther. 181: 257–272.PubMedGoogle Scholar
  27. 27.
    Harris, A.B. (1972): Degeneration in experimental epileptic foci. Arch. Neurol. 26: 434–449.PubMedCrossRefGoogle Scholar
  28. 28.
    Henn, F.A., and Hamberger, A. (1971): Glial function: uptake of trasmitter substances. Proc. Natl. Acad. Sci. U.S.A. 68: 2686–2690.PubMedCrossRefGoogle Scholar
  29. 29.
    Henn, F.A., Haljamäe, H. and Hamberger, A. (1972): Glial cell function: active control of extracellular K+ concentration. Brain Res., 43: 437–443.PubMedCrossRefGoogle Scholar
  30. 30.
    Henneman, E., Somjen, G., and Carpenter, D.O. (1965): Functional significance of cell size in spinal motoneurons. J. Neurophysiol. 28: 560–580.PubMedGoogle Scholar
  31. 31.
    Hotson, J.R., Sypert, G.W., and Ward, A.A. Jr. (1973): Extracellular potassium concentration changes during propagated seizures. Exp. Neurol. 38: 20–26.PubMedCrossRefGoogle Scholar
  32. 32.
    Hutton, J.R., Frost, J.D., and Foster, J. (1972): The influence of the cerebellum in cat penicillin epilepsy. Epilepsia, 13: 401–408.PubMedCrossRefGoogle Scholar
  33. 33.
    Jasper, H.H. (1969): Mechanisms of propagation: extracellular studies. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co., Boston, 421–438.Google Scholar
  34. 34.
    Jasper, H.H. (1972): Application of experimental models to human epilepsy. In: Experimental Models of Epilepsy, edited by D.P. Purpura, J.K. Penry, D.B. Tower, D.M. Woodbury, and R.D. Walter, 585–601. Raven Press, New YorkGoogle Scholar
  35. 35.
    Kemp, J.W., and Woodbury, D.M. (1975): The effect of Perchlorate and acetazolamide on brain excitability. Abstracts of Sixth International Congress of Pharmacology, Helsinki, Finland. 617.Google Scholar
  36. 36.
    Kimmeiberg, H.K., and Bourke, R.S. (1973): Properties and localization of bicarbonate-stimulated ATPase activity in rat brain. J. Neurochem. 20: 347–359.CrossRefGoogle Scholar
  37. 37.
    Kulenkampff, H. (1952): Das Verhalten der Neuroglia in den Vorderhörner des Rückenmarks der weissen Maus unter dem Reiz physiologischer Tätigkeit. Z. Anat. Entwicklungsgesch. 116: 304–312.CrossRefGoogle Scholar
  38. 38.
    Leao, A.A.P. (1944): Spreading depression of activity in the cerebral cortex. J. Neurophysiol. 7:359–390.Google Scholar
  39. 39.
    Lorenzo, A.V., Hedley-Whyte, E.T., Eisenberg, H.M. and Hsu, D.W. (1975): Increased penetration of horseradish peroxidase across the blood-brain barrier induced by Metrazol seizures. Brain Res. 88: 136–140.PubMedCrossRefGoogle Scholar
  40. 40.
    McQueen, J.K., and Woodbury, D.M.: Carbonic anhydrase activity and cyclic AMP levels during the development of cobalt-induced epilepsy in the rat. Submitted for publication.Google Scholar
  41. 41.
    Merlis, J. (1974): Neurophysiological aspects of epilepsy. In: Epilepsy. Proceedings of the Hans Berger Centenary Symposium, edited by P. Harris and C. Mawdsley, Churchill Livingstone, Edinburgh, 5–19.Google Scholar
  42. 42.
    Moody, W.J., Futamachi, K.J. and Prince, D.A. (1974): Extracellular potassium activity during epileptogenesis. Exp. Neurol. 42: 248–262.PubMedCrossRefGoogle Scholar
  43. 43.
    Murray, M. (1968): Effects of dehydration on the rate of proliferation of hypothalamic neuroglia cells. Exp. Neurol. 20: 460–468.PubMedCrossRefGoogle Scholar
  44. 44.
    Pope, A. (1969): Perspectives in neuropathology. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co., Boston, 773–781.Google Scholar
  45. 45.
    Prince, D.A., Lux, H.D., and Neher, E. (1973): Measurement of extracellular potassium activity in cat cortex. Brain Res. 50: 489–495.PubMedCrossRefGoogle Scholar
  46. 46.
    Ransom, B. (1974): The behavior of presumed glial cells during seizure discharge in cat cerebral cortex. Brain Res. 69: 83–99.PubMedCrossRefGoogle Scholar
  47. 47.
    Scheibel, M.E., and Scheibel, A.B. (1968): On the nature of dendritic spines-report of a workshop. Commun. Behav. Biol. 1: 231–265.Google Scholar
  48. 48.
    Schrier, B.K., and Thomson, E.J. (1974): On the role of glial cells in the mammalian nervous system. Uptake, excretion and metabolism of putative neurotransmitters by cultured glial tumor cells, J. Biol.Chem. 249:1769.PubMedGoogle Scholar
  49. 49.
    Somjen, G.G. (1975): Electrophysiology of neuroglia. Annu. Rev. Physiol. 37: 163–190.PubMedCrossRefGoogle Scholar
  50. 50.
    Spencer, W.A., and Kandel, E.R. (1969): Synaptic inhibition in seizures. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co., Boston, 575–603.Google Scholar
  51. 51.
    Van Gelder, N.M., and Courtois, A. (1972): Close correlation between changing content of specific amino acids in epileptogenic cortex of cats and severity of epilepsy. Brain Res. 43: 477–484.PubMedCrossRefGoogle Scholar
  52. 52.
    Van Gelder, N.M., Sherwin, A.C. and Rasmussen, T. (1972): Amino acid content of epileptogenic human brain: focal versus surrounding regions. Brain Res. 40: 385–393.PubMedCrossRefGoogle Scholar
  53. 53.
    Velasco, M., Velasco, F., Estrada-Villanueva, F., and Olivera, A. (1973): Alumina cream-induced focal motor epilepsy in cats. Part 1. Lesion size and temporal course. Epilepsia. 14: 3–14.PubMedCrossRefGoogle Scholar
  54. 54.
    Velasco, M., Velasco, F., Lozoya, X., Feria, A. and Gonzales-Licea, A. (1973): Alumina cream-induced focal motor epilepsy in cats. Part 2. Thickness and cellularity of cerebral cortex adjacent to epileptogenic lesions. Epilepsia, 14: 15–27.PubMedCrossRefGoogle Scholar
  55. 55.
    Vernadakis, A., Valcana, R., Curry J. J., Maletta G.J., Hudson D., and Timiras P.S. (1967): Alterations in growth of brain and other organs after electroshock in rats. Exp. Neurol. 17: 505–516.PubMedCrossRefGoogle Scholar
  56. 56.
    Ward, A.A., Jr. (1969): The epileptic neuron: chronic foci in animals and man. In: Basic Mechanisms of the Epilepsies, edited by H.H. Jasper, A.A. Ward, Jr., and A. Pope, Little, Brown and Co. Boston, 263–288.Google Scholar
  57. 57.
    Ward, A.A. (1975): Theoretical basis for surgical therapy of epilepsy. In: Advances in Neurology, Vol. 8, edited by D.P. Purpura, J.K. Penry, and R.D. Walter. Raven Press, New York, 23–35.Google Scholar
  58. 58.
    Ward, J.R., and Call, L.S. (1949): Changes in blood chemistry in rats following electrically-induced seizures. Proc. Soc. Exp. Biol. Med. 70: 381–382.PubMedGoogle Scholar
  59. 59.
    Westmoreland, B.F., Hanna, G.R. and Bass, N.H. (1972): Cortical alterations in zones of secondary epileptogenesis: a neurophysiology, morphologic and microchemical correlation study in the albino rat. Brain Res. 43: 485–599.PubMedCrossRefGoogle Scholar
  60. 60.
    Westrum, L.E., White, L.E., and Ward, A.A., Jr. (1964): Morphology of the experimental epileptic focus. J. Neurosurg. 21: 1033–1046.PubMedCrossRefGoogle Scholar
  61. 61.
    Wilder, B.J. (1972): Projection phenomena and secondary epileptogenesis mirror foci. In: Experimental Models of Epilepsy, edited by D.P. Purpura, J.K. Penry, D.B. Tower, D.M. Woodbury, and R.D. Walter, Raven Press, New York, 85–111.Google Scholar
  62. 62.
    Woodbury, D.M. (1978): Mechanisms of Action of Convulsants. In: Mechanisms of Action of Antiepileptic Drugs, edited by G. Glaser, D.M. Woodbury, and J.K. Penry, Raven Press, New York, in press.Google Scholar
  63. 63.
    Woodbury, D.M., and Esplin, D.W. (1959): Neuropharmacology and neurochemistry of anticonvulsant drugs. Proc. Assoc. Res. Nerv. Ment. Dis. 37: 24–56.Google Scholar
  64. 64.
    Woodbury, D.M., and Karler, R. (1960): Role of carbon dioxide in the nervous system. Anesthesiology, 21: 686–703.PubMedCrossRefGoogle Scholar
  65. 65.
    Woodbury, D.M. and Kemp, J.W. (1977): Basic mechanisms of seizures: neurophysiological and biochemical etiology. In: Psychpathology and Brain Dysfunction, edited by C. Shagass, S. Gershon, and A.J. Friedhof, Raven Press, New York, 149–182.Google Scholar
  66. 66.
    Woodbury, D.M., Johanson, C.E., and Brondsted, H. (1974): Maturation of the blood-brain and blood-cerebrospinal fluid transport systems. In: Narcotics and the Hypothalamus, edited by E. Zimmerman and R. George, Raven Press, New York, 225–250.Google Scholar
  67. 67.
    Woodbury, D.M., Rollins, L.T., Gardner, M.D., Hirschi, W.C., Hogan, J.R., Rallison, M.L., Tanner, G.S., and Brodie, D.A. (1958): Effects of carbon dioxide on brain excitability and electrolytes. Am. J. Physiol. 192: 79–90.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • D. M. Woodbury
    • 1
  • J. W. Kemp
    • 1
  1. 1.Department of PharmacologyUniversity of Utah College of MedicineSalt Lake CityUSA

Personalised recommendations