Abstract
The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioural and electrographic changes that can be divided in three distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24h, (b) a silent period with a progressive normalization of EEG and behaviour which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2–3 times per week per animal. Therefore, this novel and unique experimental approach may serve as a model of epilepsy mimicking the human condition.
Sommario
La somministrazione sistemica nei ratti di pilocarpina, un potente agonista muscarinico, determina modificationi sequenziali sul piano comportamentale ed elettrografico che possono essere divisi in tre periodi distinti: a) un periodo acuto che determina progressivamente uno stato epilettico a livello limbico che dura 24 h; b) un periodo silente con una progressiva normalizzazione dell'EEG e dello stato comportamentale che varia da 4 a 44 giorni; c) un periodo cronico caratterizzato da crisi spontanee ricorrenti (SRSs). Le principali caratteristiche dell'SRSs osservate sul lungo periodo sono simili a quelle che si riscontrano nelle crisi parziali complesse umane e ricorrono in ogni animale con una frequenza di 2–3 volte alla settimana. Pertanto, questo nuovo ed unico approccio sperimentale può essere utilizzato come modello di epilessia che mima la condizione patologica umana.
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References
Cavalheiro E.A., Leite, J.P., Bortolotto Z.A., Turski W.A., Ikonomidou C., Turski L.:Long-term effects of pilocarpine in rats: Structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32:778–782, 1991.
Cavazos J.E., Golarai G., Sutula T.P.:Mossy fiber synaptic reorganization induced by kindling: Time course of development, progression and permanence. J. Neurosci. 11:2795–2803, 1991.
Clifford D.B., Olney J.W., Maniotis A., Collins R.C., Zorumski C.F.:The functional anatomy and pathology of lithium-pilocarpine and high dose pilocarpine seizures. Neuroscience 23:953–968, 1987.
Eadie M.J.:Anticonvulsant therapy: Present and future. TIPS 2:37–39, 1981.
Leite J.P., Bortolotto Z.A., Cavalheiro, E.A.:Spontaneous recurrent seizures in rats: An experimental model of partial epilepsy. Neurosci. Biobehav. Rev. 14:511–517, 1990.
Leite J.P., Cavalheiro E.A.:Antiepileptic drugs and their antagonism of spontaneous seizures in rats. Epilepsia 32 (suppl. 1):35, 1991.
Lemos T., Cavalheiro E.A.:Reorganização sináptica e ocorrência de crises espontâneas em ratos. J. Liga Bras. Epil. 5:135–138, 1991.
Meldrum B.C.:Preclinical test systems for evaluation of novel compounds. In: B.S. Meldrum, R.J. Porter (eds.) New anticonvulsant drugs. London: John Libbey, pp. 31–48, 1986.
Mello L.E.A.M., Cavalheiro E.A., Tan A.M., Kupfer W.R., Pretorius J.K., Babb T.L., Finch D.M.:Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: Cell loss and mossy fiber sprouting. Epilepsia, 39:985–995, 1993.
Nadler J.V., Perry B.W., Cotman C.W.:Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid. Brain Res. 182:1–9, 1980.
Olney J.W.:Inciting excitotoxic cytocide among central neurons. In: Y. Ben-Ari, R. Schwarcz. (eds.) Excitatory Amino Acids and Seizure Disorders. New York: Plenum Press, pp. 631–645, 1986.
Racine R.J.:Modification of seizure activity by electrical stimulation. II. Motor seizure. EEG Clin. Neurophysiol. 32:281–284, 1972.
Steward O., Vinsant S.L., Davis L.:The process of reinnervation in the dentate gyrus of adult rats: An ultrastructural study of changes in presynaptic terminals as a result of sprouting. J. Comp. Neurol. 267:24–33, 1988.
Turski L., Cavalheiro E.A.:Seizures induced by pilocarpine: Relevance in epilepsy. In: N.N. Osborne (ed.) Current Aspects of the Neurosciences. New York: The Macmillan Press pp. 127–158, 1992.
Turski W.A., Czuczwar S.J., Cavalheiro E.A., Turski L., Kleinrok Z.:Acute and long-term effects of systemic pilocarpine in rats: spontaneous recurrent seizures as a possible model of temporal lobe epilepsy. Naunyn-Schmiedeberg's Arch. Pharmacol., 324:25R, 1983.
Turski W.A., Cavalheiro E.A., Schwarz M., Czuczwar S.J., Kleinrok Z. Turski L.:Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study. Behav. Brain Res. 9:315–335, 1983.
Turski W.A., Cavalheiro E.A., Bortolotto Z.A., Mello L.E.A.M., Schwarz M., Turski L.:Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brains Res. 321, 237–253, 1984.
Turski L., Cavalheiro E.A., Sieklucka-Dziuba M., Ikonimidou-Turski C., Czuczwar S.J., Turski W.A.:Seizures produced by pilocarpine: neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain Brain Res. 398:37–48, 1986.
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This research was supported by FAPESP, CNPq and FINEP from Brazil.
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Cavalheiro, E.A. The pilocarpine model of epilepsy. Ital J Neuro Sci 16, 33–37 (1995). https://doi.org/10.1007/BF02229072
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DOI: https://doi.org/10.1007/BF02229072