Skip to main content
SpringerLink
Log in

Suppression of pilocarpine-induced status epilepticus and the late development of epilepsy in rats

  • Original Paper
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Status epilepticus (SE) has been related to subsequent development of epilepsy. The present work was aimed at elucidating the relationship between the duration of pilocarpine- (PILO)-induced SE and the subsequent development of epilepsy in rats. The latency for the appearance of the first spontaneous seizure, the frequency of spontaneous seizures, the cell density in the hippocampal formation and the density of supragranular neo-Timmstaining were monitored. At 30 min, 1, 2 and 6 h after the beginning of SE, animals were treated with diazepam plus pentobarbital. In non-treated rats, SE remitted spontaneously. Animals exhibiting 30 min of PILO-induced SE did not develop spontaneous seizures. Hippocampal cell counts and the density of neo-Timm staining in these animals were similar to those observed in control rats. In the other groups longer SE durations were related to: shorter latency for the appearance of the first spontaneous seizure, increased number of the spontaneous recurrent seizures, severe cell loss in the hippocampal formation, or increased supragranular neo-Timm staining. These data suggest that more than 30 min of SE is required to produce hippocampal damage with subsequent synaptic reorganization of the mossy fibre pathway that could account for SRSs observed in the PILO model of epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239–247

    Google Scholar 

  • Aicardi J, Chevrie JJ (1983) Consequences of status epilepticus in infants and children. Adv Neurol 34:115–25

    Google Scholar 

  • Babb TL, Kupfer WR, Pretorius JK, Crandall PH, Levesque MF (1991) Synaptic recurrent excitation of granule cells by mossy fibers in human epileptic hippocampus. Neuroscience 42:351–63

    Google Scholar 

  • Babb TL, Pretorius JK, Mello LE, Mathern GW, Levesque MF (1992) Synaptic reorganization in epileptic human and rat kainate hippocampus may contribute to feedback and feedforward excitation. Epilepsy Res [Suppl] 9:193–203

    Google Scholar 

  • Barker JL (1975) CNS depressants: effects on postsynaptic pharmacology. Brain Res 93:77–90

    Google Scholar 

  • Brown A, Horton J (1967) Status epilepticus treated by intravenous infusion of thiopentone sodium. BMJ 1:27–8

    Google Scholar 

  • Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L (1991) Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32:778–82

    Google Scholar 

  • Clifford DB, Olney JW, Maniotis A, Collins RC, Zorunski CF (1987) The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience 23:953–68

    Google Scholar 

  • Corsellis JAN, Bruton CJ (1983) Neuropathology of status epilepticus in humans. Adv Neurol 34:129–139

    Google Scholar 

  • Coyle JT (1983) Neurotoxic action of kainic acid. J Neurochem 41:1–11

    Google Scholar 

  • Cronin J, Obenaus A, Houser CR, Dudek FE (1992) Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of mossy fiber. Brain Res 573:305–10

    Google Scholar 

  • Danscher G (1981) Histochemical demonstration of heavy metals — a revised version of the silver sulphide method suitable for both light and electron microscopy. Histochemistry 71:1–16

    Google Scholar 

  • Jope RS, Morrisett RA, Snead OC (1986) Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats. Exp Neurol 97:193–200

    Google Scholar 

  • Kleijn E van der, Schobbes F, Termond E, Janssen W, Vree TB (1983) Clinical pharmacokinetics and therapeutic application of antiepileptic drugs. Res Publ Assoc Res Nerv Ment Dis 61:143–69

    Google Scholar 

  • Leite JP, Bortolotto ZA, Cavalheiro EA (1990) Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci Biobehav Rev 14:511–7

    Google Scholar 

  • Lemos T, Cavalheiro EA (1992) Reorganização sinaptica e ocorrência de crises espontâneas em ratos. J Liga Bras Epil 5:135–8

    Google Scholar 

  • Mathern GW, Cifuentes F, Leite JP, Pretorius JK, Babb TL (1993) Hippocampal EEG excitability and chronic spontaneous seizures are associated with aberrant synaptic reorganization in the rat intrahippocampal kainate model. Electroencephalogr Clin Neurophysiol 87:326–339

    Google Scholar 

  • Meldrum BS (1993) Excitotoxicity and selective neuronal loss in epilepsy. Brain Pathol 3:404–412

    Google Scholar 

  • Meldrum BS, Bruton CJ (1992) Epilepsy. In: Adams JH, Duchen LW (ed) Greenfield's Neuropathology. Edward Arnold, London, Melbourne, Auckland, pp 1246–1283

    Google Scholar 

  • Mello LEAM, Cavalheiro EA, Tan AM, Kupfer WR, Pretorius JK, Babb TL, Finch DM (1993) Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia 34:985–995

    Google Scholar 

  • Monaghan DT, Cotman CW (1985) Distribution of N-methyl-D-aspartate-sensitive l-[O3H]-glutamate binding sites in rat brain. J Neurosci 5:2909–2929

    Google Scholar 

  • Mouritzen-Dam A (1982) Hippocampal neuron loss in epilepsy and after experimental seizures. Acta Neurol Scand 66:601–42

    Google Scholar 

  • Norman RN (1964) The neuropathology of status epilepticus. Med Sci Law 4:45–61

    Google Scholar 

  • Olney JW (1983) Excitotoxins: an overview. In: Fuxe K, Roberts P, Schwarcz R (eds) Excitotoxins. Macmillan, London, 82–96

    Google Scholar 

  • Olney JW, Collins RC, Sloviter RS (1986) Excitotoxic mechanisms of epileptic brain damage. Adv Neurol 44:857–77

    Google Scholar 

  • Ounsted C, Lindsay J, Norman R (1966) Biological factors in temporal lobe epilepsy. (Clinics in developmental medicine, vol 22) Heinemann Medical, London

    Google Scholar 

  • Pellegrino LJ, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Appleton-Century-Crofts, New York

    Google Scholar 

  • Sagar HJ, Oxbury JM (1987) Hippocampal neurone loss in temporal lobe epilepsy: correlation with early childhood convulsions. Ann Neurol 22:334–340

    Google Scholar 

  • Samson FE, Pazdernik TL, Cross RS, Churchill L, Giesler MP, Nelson SR (1985) Brain regional activity and damage associated with organophosphate induced seizures: effect of atropine and benactyzine. Proc West Pharmacol Soc 28:183–5

    Google Scholar 

  • Sloviter RS (1982) A simplified Timm stain procedure compatible with formaldehyde fixation and routine paraffin embedding of rat brain. Brain Res Bull 8:771–774

    Google Scholar 

  • Sloviter RS (1991) Permanently altered hippocampal structure, excitability, and inhibition after status epilepticus in the rat: the “dormant basket cell” hypotheses and its possible relevance to temporal lobe epilepsy. Hippocampus 1:41–66

    Google Scholar 

  • Sloviter RS (1992) Possible functional consequences of synaptic reorganization in the dentate gyrus of kainate-treated rats. Neurosci Lett 137:91–6

    Google Scholar 

  • Sutula T, Xiao-Xian H, Cavazos J, Scott G (1988) Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science 239:1147–50

    Google Scholar 

  • Sutula T, Cascino G, Cavazos J, Parada I, Ramirez L (1989) Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol 26:321–30

    Google Scholar 

  • Tauck DL, Nadler JV (1985) Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J Neurosci 5:1016–22

    Google Scholar 

  • Turski WA, Cavalheiro EA, Schwarz M, Czucwar SJ, Kleinrok Z, Turski L (1983) Limbic seizures produced by pilocarpine in rats: behavioral electroencephalographic and neuropathological study. Behav Brain Res 9:315–335

    Google Scholar 

  • Turski WA, Cavalheiro EA, Bortolotto ZA, Mello LEAM, Schwarz M, Turski L (1984) Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res 321:237–253

    Google Scholar 

  • Turski L, Ikonomidou C, Turski WL, Bortolotto ZA, Cavalheiro EA (1989) Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse 3:154–71

    Google Scholar 

  • Walton NW, Treiman DM (1988) Response of status epilepticus induced by lithium and pilocarpine to treatment with diazepam. Exp Neurol 101:267–75

    Google Scholar 

  • Williams S, Vachon P, Lacaille JC (1993) Monosynaptic GAB-Amediated inhibitory postsynaptic potential in CA1 pyramidal cells of hyperexcitable hippocampal slices from kainic acid-treated rats. Neuroscience 52:541–54

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurologia Experimental, Escola Paulista de Medicina, R. Botucatu, 862, 04023-900, Sào Paulo, Brazil

    Tadeu Lemos & Esper A. Cavalheiro

Authors
  1. Tadeu Lemos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esper A. Cavalheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lemos, T., Cavalheiro, E.A. Suppression of pilocarpine-induced status epilepticus and the late development of epilepsy in rats. Exp Brain Res 102, 423–428 (1995). https://doi.org/10.1007/BF00230647

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00230647

Key words

Search

Navigation