Hostname: page-component-669899f699-g7b4s Total loading time: 0 Render date: 2025-04-27T01:34:07.270Z Has data issue: false hasContentIssue false
  • English
  • Français

Epilepsy: Relationships Between Electrophysiology and Intracellular Mechanisms Involving Second Messengers and Gene Expression

Published online by Cambridge University Press:  18 September 2015

P. Gloor
P. Gloor*
Affiliation:
Department of Neurology and Neurosurgery of McGill University and the Montreal Neurological Institute
*
Montreal Neurological Institute, 3801 University St., Montreal, Quebec, Canada H3A 2B4
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

It is well known that pure absence epilepsy is a benign form of seizure disorder, while most others, particularly partial and convulsive seizures may have transient or permanent deleterious consequences and are more difficult to bring under therapeutic control by anticonvulsants. The hypothesis is proposed that the preservation of GABA-ergic inhibition in absence attacks and its breakdown in most other seizures may explain these differences. Breakdown of GABA-ergic inhibition allows NMDA receptors to become active. This opens the way for Ca2+ to enter the cell. Such Ca2+ entry is a long-lasting phenomenon. It is likely to be massive during most seizures except during absence attacks, and may therefore damage the neuron transiently or permanently. It may even destroy it. Ca2+ entry is also a crucial factor in the activation of the second messenger cascade which involves cytosolic as well as nuclear (genomic) components. Activation of this cascade converts short-lived electrophysiological processes occurring at the membrane into much longer-lasting intracellular processes. These may include plastic changes at the synaptic and receptor level and may account for kindling and the increasing therapy-resistance of long-standing seizure disorders. Changes resulting from massive Ca2+ entry into the neuron may explain why most seizures, except absence attacks, may have deleterious consequences of various kinds, some short-lived, some of longer duration, and some even permanent.

Type
Special Features
Information
Canadian Journal of Neurological Sciences , Volume 16 , Issue 1 , February 1989 , pp. 8 - 21
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

1.Gastaut, H. “Benign″ or “functional″ (versus “organic″) epilepsies in different stages of life: an analysis of the corresponding agerelated variations in the predisposition to epilepsy. In: Broughton, RF, ed.Henri Gastaut and the Marseilles School’s Contribution to the Neurosciences. Electroenceph Clin Neurophysiol 1982;35: 17–44.Google Scholar
2.Lennox, WG, Lennox, MA. Epilepsy and related disorders. Boston: Little, Brown , 1960; 1.Google Scholar
3.Dalby, MA. Epilepsy and 3 per second spike and wave rhythms. A clinical, electroencephalographic and prognostic analysis of 346 patients. Acta Neurol Scand 1969; 45, 40: 183.Google Scholar
4.Gastaut, H, Zifkin, BG. Classification of the epilepsies. J Clin Neurophysiol 1985; 2: 313–326.CrossRefGoogle ScholarPubMed
5.Loiseau, P. Childhood absence epilepsy. In: Roger, J, Dravet, C, Bureau, M, Dreifuss, FE, Wolf, P eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. London: John Libby, 1985; 106–120.Google Scholar
6.Berkovic, SF, Andermann, F, Andermann, E, Gloor, P. Concepts of absence epilepsies: discrete syndromes or biological continuum?. Neurology 1985; 37: 993–1000.CrossRefGoogle Scholar
7.Janz, D. Neurological morbidity of severe epilepsy. Epilepsia 1988; 29, 1: S1–S8.CrossRefGoogle ScholarPubMed
8.Wolf, P, Inoue, Y. Therapeutic response of absence seizures in patients of an epilepsy clinic for adolescents and adults. J Neurology. 1984; 231: 225–229.CrossRefGoogle ScholarPubMed
9.Gastaut, H, Zifkin, BG, Mariani, E, Puig, JS. The long-term course of primary generalized epilepsy with persisting absences. Neurology. 1986; 36: 1021–1028.CrossRefGoogle ScholarPubMed
10.Gloor, P. Generalized epilepsy with spike-and-wave discharge: a reinterpretation of its electrographic and clinical manifestations. Epilepsia. 1979; 20: 571–588.CrossRefGoogle ScholarPubMed
11.Gloor, P. Electrophysiology of generalized epilepsy. In: Schwartzkroin, J, Dravet, PA, Wheal, H, eds. Electrophysiology of Epilepsy. London: Academic Press, 1984; 107–136.Google Scholar
12.Kostopoulos, G, Avoli, M, Gloor, P. Participation of cortical recurrent inhibition in the genesis of spike and wave discharges in feline generalized penicillin epilepsy. Brain Res. 1983; 267: 101–112.CrossRefGoogle ScholarPubMed
13.Giaretta, D, Kostopoulos, G, Gloor, P, Avoli, M. lntracortical inhibitory mechanisms are preserved in feline generalized penicillin epilepsy. Neuroscience Lett. 1985; 99: 203–208.CrossRefGoogle Scholar
14.Kostopoulos, G. Neuronal sensitivity to GABA and glutamate in generalized epilepsy with spike and wave discharges. Exp Neurol. 1986; 92: 20–36.CrossRefGoogle ScholarPubMed
15.Giaretta, D, Avoli, M, Gloor, P. Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized penicillin epilepsy. Brain Res. 1987; 405: 68–79.CrossRefGoogle ScholarPubMed
16.Gloor, P, Fariello, RG. Generalized epilepsy: some of its cellular mechanisms differ from those of focal epilepsy. Trends in Neurosci. 1988; 11: 63–68.CrossRefGoogle ScholarPubMed
17.Spielmeyer, W. Die Pathogenese des epileptischen Krampfes. Z ges Neurol Psychiat. 1927; 109: 501–520.CrossRefGoogle Scholar
18.Margerison, JH, Corsellis, JAN. Epilepsy and the temporal lobes. Brain. 1966; 109 2: 499–530.CrossRefGoogle Scholar
19.Ounsted, C, Norman, R. Biological factors in temporal lobe epilepsy. In: eds. Clinics in Developmental Medicine NO.22. London: The Lavenham Press Ltd, 1966; 135.Google Scholar
20.Mouritzen Dam, A. Hippocampal neuron loss in epilepsy and after experimental seizures. Acta Neurol Scand. 1982; 66: 601–642.Google Scholar
21.Sagar, HJ, Oxbury, JM. Hippocampal neuron loss in temporal lobe epilepsy: correlation with early childhood convulsions. Ann Neurol. 1987; 22: 334–340.CrossRefGoogle ScholarPubMed
22.Gowers, WR. Epilepsy and other chronic convulsive states. London: Churchill, 1881.Google Scholar
23.Reynolds, EH, Elwes, RDC, Shorvon, SD. Why does epilepsy become intractable?. Lancet 1983; 2: 952–954.CrossRefGoogle ScholarPubMed
24.Reynolds, EH. The prevention of chronic epilepsy. Epilepsia 1988; 29,1: 525–528.CrossRefGoogle ScholarPubMed
25.Taylor-Courval, D, Gloor, P. Behavioral alterations associated with generalized spike and wave discharges in the EEG of the cat. Exp Neurol 1984; 83: 167–186.CrossRefGoogle ScholarPubMed
26.Guberman, A, Gloor, P, Sherwin, AL. Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin. Neurol 1975; 25: 758–764.CrossRefGoogle ScholarPubMed
27.Pellegrini, A, Gloor, P, Sherwin, AL. Effect of valproate sodium on generalized penicillin epilepsy in the cat. Epilepsia 1978; 19: 351–360.CrossRefGoogle ScholarPubMed
28. Kostopoulos, G, Gloor, P, Pellegrini, A, Siatitsas, I. A study of the transition from spindles to spike and wave discharge in feline generalized penicillin epilepsy: EEG features. Exp Neurol 1981; 73: 43–54.CrossRefGoogle ScholarPubMed
29. Kostopoulos, G, Gloor, P, Pellegrini, A, Gotman, J. A study of the transition from spindles to spike and wave discharge in feline generalized penicillin epilepsy: microphysiological features. Exp Neurol 1981; 73: 55–77.CrossRefGoogle ScholarPubMed
30.McLachlan, RS, Avoli, M, Gloor, P. Transition from spindles to generalized spike and wave discharge in the cat: simultaneous single-cell recordings in cortex and thalamus. Exp Neurol 1984; 85: 413–425.CrossRefGoogle ScholarPubMed
31.Avoli, M, Gloor, P, Kostopoulos, G, Gotman, J. An analysis of penicillin-induced generalized spike and wave discharges using simultaneous recordings of cortical and thalamic single neurons. J Neurophysiol 1983; 50: 819–837.CrossRefGoogle ScholarPubMed
32.Curtis, DR, Game, CJA, Johnston, GAR, McCullock, RM, MacLachlan, RM. Convulsive action of penicillin. Brain Res 1972; 43: 242–245.CrossRefGoogle ScholarPubMed
33.Davidoff, RA. Penicillin and inhibition in the cat spinal cord. Brain Res. 1972; 45: 638–642.CrossRefGoogle ScholarPubMed
34.Prince, DA. Neurophysiology of epilepsy. Annu Rev Neurosci. 1978; 1: 395–415.CrossRefGoogle ScholarPubMed
35.Dingledine, R, Gjerstad, L. Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J Physiol (London) 1980; 297: 313–245.Google Scholar
36.Schwartzkroin, PA, Prince, DA. Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 1980; 183: 61–76.CrossRefGoogle ScholarPubMed
37.Kmjevic, KGABA-mediated inhibitory mechanisms in relation to epileptic discharges. In: Jasper, H, van Gelder, N, eds. Basic Mechanisms of Neuronal Hyperexcitability. New York: Alan R. Liss, Inc, 1983; 249–280Google Scholar
38.Quesney, LF, Gloor, P. Generalized penicillin epilepsy in the cat: correlation between electrophysiological data and distribution of l4C-penicillin in the brain. Epilepsia 1978; 19: 35–45.CrossRefGoogle ScholarPubMed
39.Avoli, M, Siatitsas, I, Kostopoulos, G, Gloor, P. Effects of post-ictal depression on experimental spike and wave discharges. Electroenceph Clin Neurophysiol 1981; 52: 372–374.3.CrossRefGoogle ScholarPubMed
40.Ben-Ari, Y, Krnjevic, K, Reinhardt, W. Hippocampal seizures and failure of inhibition. Can J Physiol Pharmacol 1979; 57: 1462–1466.CrossRefGoogle Scholar
41.Ben-Ari, Y, Krnjevic, K. Actions of GAB A on hippocampal neurons with special reference to the aetiology of epilepsy. In: Morselli, PL, LÖscher, W, Lloyd, RG, Meldrum, MB, Reynolds, EH eds. Neurotransmitters, Seizures, and Epilepsy. New York: Raven Press, 1981; 63–73Google ScholarPubMed
42.Traub, RD, Wong, RKS. Cellular mechanism of neuronal synchronization in epilepsy. Science 1982; 216: 745–747.CrossRefGoogle ScholarPubMed
43.Traub, RD, Wong, RKS. Synchronized burst discharge in disinhibited hippocampal slice. II. Model of cellular mechanism. J Neurophysiol 1983; 459: 471–747.Google Scholar
44.Avoli, M. Is epilepsy a disorder of inhibition or excitation?. In: epilepsy: Nistico, G, DiPerri, R, Meinhardt, H eds. An Update on Research and Therapy (Progress in Clinical and Biological Research). New York: Alan R Liss, Inc. 1983: 124: 23–37Google Scholar
45.Matsumoto, H, Ajmone Marsan, C. Cortical cellular phenomena in experimental epilepsy: interictal manifestations. Exp Neurol 1964; 9: 286–304.CrossRefGoogle ScholarPubMed
46.Dichter, M, Spencer, WA. Penicillin-induced interictal discharges from the cat hippocampus. I. Characteristics and topographical features. J Neurophysiol 1969; 32: 649–662.CrossRefGoogle ScholarPubMed
47.DWong, RKS, Prince, DA. Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 1978; 159: 385–390.Google Scholar
48.Coutinho-Netto, J, Abdul-Ghani, AS, Collins, JF, Bradford, HF. Is glutamate a trigger factor in epileptic hyperactivity?. Epilepsia 1981; 22: 289–296.CrossRefGoogle ScholarPubMed
49.Herron, CE, Williamson, R, Collingridge, GL. A selective N-methyl-D-aspartate antagonist depresses epileptiform activity in rat hippocampal slices. Neurosci Lett 1985; 61: 255–260.CrossRefGoogle ScholarPubMed
50.Dingledine, R. NMDA receptors. What do they do?. Trends in Neurosci 1986; 9: 47–49.CrossRefGoogle Scholar
51.Avoli, M, Olivier, A. Bursting in human epileptogenic neocortex is depressed by an N-methyl-D-aspartate antagonist. Neurosci Lett 1987; 76: 249–254.CrossRefGoogle ScholarPubMed
52.Cotman, CW, Monaghan, DT, Ganong, AH. Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Annu Rev Neurosci 1988; 11: 61–80.CrossRefGoogle ScholarPubMed
53.Mayer, ML, Westhook, GL, Guthrie, PH. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 1984; 309: 262–263.CrossRefGoogle ScholarPubMed
54.Nowak, L, Bregestovski, P, Ascher, P, Herbert, A, Prochiantz, A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 1984; 307: 462–465.CrossRefGoogle ScholarPubMed
55.MacDermott, AB, Mayer, ML, Westbrook, GL, Smith, SJ, Barker, JL. NMDA-receptor activation increases cytoplasmic calcium concentration concentration in cultured spinal neurones. Nature 1986; 321: 519–522.CrossRefGoogle Scholar
56.Jahr, CE, Stevens, CF. Glutamate activates multiple single channel conductances in hippocampal neurones. Nature 1987; 325: 522–525.CrossRefGoogle Scholar
57.Mayer, ML, MacDermott, AB, Westbrook, GL, Smith, SJ, Barker, JL. Agonist and voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp. J Neurosci 1987; 7: 3230–3244.CrossRefGoogle ScholarPubMed
58.Collingridge, GL, Bliss, TVP. NMDA receptors - their role in longterm potentiation. Trends in Neurosci 1987; 10: 288–293.CrossRefGoogle Scholar
59.Cotman, CW, Iversen, LL. Excitatory amino acids in the brain -focus on NMDA receptors. Trends in Neurosci 1987; 10: 263–265.CrossRefGoogle Scholar
60.Nicoll, RA, Kauer, JA, Malenka, RC. The current excitement in long term potentiation. Neuron 1988; 1: 97–103.CrossRefGoogle ScholarPubMed
61.Matsumoto, H, Ajmone Marsan, C. Cortical cellular phenomena in experimental epilepsy: ictal manifestations. Exp Neurol 1964b; 9: 305–326.CrossRefGoogle ScholarPubMed
62.Ayala, GF, Matsumoto, H, Gumnit, RJ. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J Neurophysiol 1970; 33: 73–85.CrossRefGoogle ScholarPubMed
63.Heinemann, U, Lux, HD, Gutnick, MJ. Extracellular free calcium and potassium during paroxysmal activity in the cerebral cortex of the cat. Exp Brain Research 1977; 27: 237–243.Google ScholarPubMed
64.Louvel, J, Heinemann, U. Changes in [Ca2+]0, [K+]n and neuronal activity during oenanthotoxin-induced epilepsy in cat sensorimotor cortex. Electroenceph Clin Neurophysiol 1983; 56: 457–466.CrossRefGoogle Scholar
65.Pumain, R, Ménini, C, Heinemann, U, Louvel, J, Siva-Barrat, C. Chemical synaptic transmission is not necessary for epileptic seizures to persist in the baboon Papio papio. Exp Neurol 1985; 89: 250–258.CrossRefGoogle Scholar
66.Heinemann, U, Hamon, B. Calcium and epileptogenesis. Exp Brain Res 1986; 65: 1–10.CrossRefGoogle ScholarPubMed
67.Avoli, M, Louvel, J, Pumain, R, Olivier, A. Seizure-like discharges induced by lowering [Mg2+]0 in the human epileptogenic neocortex maintained in vitro. Brain Research 1987; 417: 199–203.CrossRefGoogle Scholar
68.Connor, JA, Wadman, WJ, Hockberger, PE, Wong, RKS. Sustained dendritic gradients of Ca2+ induced by excitatory amino acids in CA1 hippocampal neurons. Science 1988; 240: 649–653.CrossRefGoogle ScholarPubMed
69.Greengard, P. Neuronal phosphoproteins, mediators of signal transduction. Molecular Neurobiol 1987; 1: 81–119.CrossRefGoogle ScholarPubMed
70.Goelet, P, Castellucci, VF, Schacher, S, Kandel, ER. The long and the short of long-term memory - a molecular framework. Nature 1986; 322: 419–422.CrossRefGoogle Scholar
71.Miller, RJ. Protein kinase C: a key regulator of neuronal excitability?. Trends in Neurosci 1986; 9: 538–541.CrossRefGoogle Scholar
72.Pfenninger, KH. Of nerve growth cones, leukocytes and memory: second messenger systems and growth-regulated proteins. Trends in Neurosci 1986; 9: 562–565.CrossRefGoogle Scholar
73.Schwartz, JJ and Greenberg, SM. Molecular mechanisms for memory: second-messenger induced modifications of protein kinases in nerve cells. Annu Rev Neurosci 1987; 10: 459–476.CrossRefGoogle ScholarPubMed
74.Griffiths, T, Evans, MC, Meldrum, BS. Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allyglycine. Neurosci 1983; 10: 385–395.CrossRefGoogle ScholarPubMed
75.Olney, JW, Collins, RC, Sloviter, RS. Excitotoxic mechanisms of epileptic brain damage. In: Delgado-Escueta, AV, Ward, AA Jr, Woodbury, DM, Porter, RJ eds. Advances in Neurology. New York: Raven Press. 1986: 44: 857–877Google Scholar
76.Rothman, SM, Olney, JW. Excitotoxicity and the NMDA receptor. Trends in Neurosci; 10: 299–302.CrossRefGoogle Scholar
77.Sloviter, RS. “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. 1. Acute electrophysiological and light microscopic studies. Brain Res Bull; 1983; 10: 675–697.CrossRefGoogle Scholar
78.Lynch, G, Baudry, M. The biochemistry of memory: a new and specific hypothesis. Science 1984; 12: 1057–1063.CrossRefGoogle Scholar
79.Black, IB, Adler, JE, Dreyfus, CF, Friedman, WF, LaGamma, EF, Roach, AH. Biochemistry of information storage in the nervous system. Science 1987; 236: 1263–1268.CrossRefGoogle ScholarPubMed
80.Routtenberg, A, Lovinger, D, Steward, O. Selective increase in phos-phosylation of a 47kDa protein (Fl) directly related to long-term potentiation. Behav Neurol Biol 1985; 43: 3–11.CrossRefGoogle Scholar
81.Morgan, JI, Cohen, DR, Hempstead, JL, Curran, T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science 1987; 237: 192–197.CrossRefGoogle ScholarPubMed
82.Greenberg, ME, Ziff, EB, Greene, LA. Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 1988; 234: 80–83.CrossRefGoogle Scholar
83.Gubits, RM, Hazelton, JL, Simantov, R. Variations in c-fos gene expression during rat brain development. Molecular Brain Res 1988; 3: 197–202.CrossRefGoogle Scholar
84.Morgan, JI, Curran, T. Role of ion flux in the control of c-fos expression. Nature 1986; 322: 552–555.CrossRefGoogle ScholarPubMed
85.Dragunow, M, Robertson, HA. Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus. Nature 1987; 329: 441–442.CrossRefGoogle ScholarPubMed
86.Dragunow, M, Robertson, HA. Localization and induction of c-fos protein-like immunoreactive material in the nuclei of adult mammalian neurons. Brain Res 1988; 440: 252–260.CrossRefGoogle ScholarPubMed
87.Mody, I, Heinemann, U. NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling. Nature 1987; 326: 701–704.CrossRefGoogle ScholarPubMed
88.Sherwin, A, Robitaille, Y, Quesney, L, Reader, T, Olivier, A, Briere, R, Andermann, E, Andermann, F, Feindel, W, Leblanc, R, Matthew, E, Ochs, R, Villemure, J, Gloor, P. Noradrenergic abnormalities in human cortical seizure foci. In: Engel, J, Ojemann, GA, Luders, HO, Williamson, PD eds. Fundamental Mechanisms of Human Brain Function. New York: Raven Press . 1987; 249–258Google Scholar