J Korean Neurol Assoc.  1996 Mar;14(1):74-88.

Characteristics of Lithium-Pilocarpine Seizure Model: Behaviors, Electroencephalography, Fos Expression and Neuropathologic changes

• Kim YI
• Lee KS
• Kim BS
• Kim YJ
• Chun MH
• Kim MS

Abstract

It is well known that the status epilepticus induced by the administration of pilocarpine to lithium-pretreated rats is a role model to study for the cholinergic system in epileptogenesis and the pathogenesis of status epilepticus. Although the researches for the expression of the c-fos proto-oncogene in seizure models have been studied, the exact role of the c-fos expression is still uncertain. To evaluate the characteristics of lithium-pilocarpine seizure model, we designed this study by following three steps; (1) the analysis of clinical manifestations by video, and electroencephalogram through implanted cortical electrodes during the course of status epilepticus induced by intraperitoneal administration of lithium chloride (5 mEq/kg) followed by pilocarpine(50 mg/kg) in Sprague-Dawley rats, (2) Fos expression and the time course of Fos appearance by the immunocytochemistry, (3) Neuropathologic change by cresyl violet stain. The presentation of clinical manifestations were cholinergic symptoms and signs, stereotyped behaviour, motor seizures, and status epilepticus in order. Electroencephalographic findings showed five patterns : (I) discrete seizure with interictal slowing; (ii) merging seizures with waxing and waning ictal discharges; (iii) continuous ictal discharges; (iv) continuous ictal discharges with flat periods; and (v) periodic epileptiform discharges on a flat background. The neuroanatomical sites of Fos expression were the taenia recta, anterior olfactory nucleus, olfactory tubercle, piriform cortex, entorhinal cortex, amygdala, septum, accumbens, caudate-putamen, hippocampus, dentate gyrus, thalamus, and cerebral neocortex. The Fos immunostaining appeared first in the taenia tecta, anterior olfactory nucleus, olfactory tubercle, and piriform cortex at 1 hour after pilocarpine injection, and was maximal in the most areas of cerebral cortex and limbic area between 4 and S hours. The thalamus and the caudate-putamen became stained after 4 hours. In the hippocampal formation, firstly, the Fos was stained maximally in the dentate gyrus at 3 hours followed by in the CA1, CA2, and CA3 regions. The Fos was disappeared in the dentate gyrus and CA2 region of hippocampus within 18 hours, but became stained sustainly in the CA3 and CA1 regions of hippocampus at 24 hours. Llght microscopic findings revealed widespread brain damage. The neuropathological changes were found within the anterior olfactory nucleus, piriform cortex, entorhinal cortex, thalamus, hippocampal formation, amygdaloid complex, lateral septum, neocortex and substantia nigra. There were only swollen and edematous change of neurons at 1 hour, but severely shrunken and darkened neuronal degeneration and neuronal loss at 72 hours. The neuronal degeneration and loss in hippocampal formation appeared severe in the CA1 and hilum, moderate in CA2, and mild in CA3 and dentate gyrus. In conclusion, it was suggested that cholinergic system (muscarinic receptor) played an important role in the induction of the seizure because Fos was expressed in the brain areas containing muscarinc receptor and the lithium-pilocarpine seizure was a good model to study for the status epilepticus.

MeSH Terms

Amygdala
Animals
Brain
Cerebral Cortex
Dentate Gyrus
Electrodes
Electroencephalography*
Entorhinal Cortex
Genes, fos
Hippocampus
Immunohistochemistry
Lithium Chloride
Neocortex
Neurons
Olfactory Pathways
Pilocarpine
Rats
Rats, Sprague-Dawley
Seizures*
Status Epilepticus
Substantia Nigra
Taenia
Thalamus
Viola
Lithium Chloride
Pilocarpine