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KMID : 0350519960490020547
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Journal of Catholic Medical College
1996 Volume.49 No. 2 p.547 ~ p.562
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Fos Expression and morphological Changes in Lithium-Pilocarpine Induced Generalized Convulsive Status Epilepticus Rat Brain
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Lee Kwang-Soo
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Abstract
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It is well known that the status epilepticus induced by 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 Fos (c-fos protein) in seizure models have been studied the exact role of the Fos expression is still unknown. To investigate the spreading pathways of seizure and the correlation between the Fos expression and the neuropathologic change, we designed this study by following three steps; (1) the observation of status epilepticus induced by intraperitoneal addministration of lithium chloride (211 mg/kg) followed by pilocarpine (50 mg/kg) 24 hours later in Sprague-Dawley rats, (2) the time-course effect of Fos expression by immunohistochemistry, (3) Neuropathologic change by cresyl violet stain. The observed clinical manifestations after drug treatment were those including cholinergic symptoms and signs, stereotyped behavior, motor seizures, and status epilepticus in order. The neuroanatomical areas of Fos expression were the taenia tecta, anterior olfactory nucleus, olfactory tubercle, piriform cortex, entorhinal cortex, amygdala, septum, accumbens, caudate-putamen, hippocampus, dentate gyrus, thalamus, and cerebral neocortex. Immunohistochemically, Fos expressions were first appeared in the taenia tecta, anterior olfactory nucleus, olfactory tubercle, and piriform cortex at 1 hour after pilocarpine injectin, and was maximal in most areas of cerebral cortex and limbic area between 4 and 5 hours. The thalamus and the caudate-putamen became stained 4 hours after injection. 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 was stained sustainedly in the CA3 and CA1 regions of hippocampus at 24 hours. Light 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 swelling 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 neuronal loss at 72 hours. The neuronal degeneration and loss in hippocampal formation appeared severely in the CA1 and hilum, moderately in CA2, and mildly in CA3 and dentate gyrus. In conclusion, it is suggested that cholinergic system(muscarinic receptor) plays an important role in the induction of the seizure because Fos expression appears early in the brain areas such as taenia tecta, olfactory tubercle and piriform cortex containing muscarinic receptor, and the recruitment of certain subcortical structures, mainly the basal ganglia and midline thalamic nuclei, seems to be the critical event in the generalization of lithium-pilocarpine induced seizure. Although the neuropathological changes were observed in the neuroanatomical areas of the Fos expression, because not all of the neurons expressing the Fos were commited to die, it could be thought that the Fos expression is not a direct indicator of the neuropathological change. Therefore, further study to ascertain the other factors to neropathological changes may be required.
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KEYWORD
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