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Ultrastructural study of hippocampal cortex neurons in an experimental model of valproate encephalopathy
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Abstract
Valproate (VPA) is a widely used antiepileptic drug. A serious neurological-outcome defined as valproate encephalopathy (VE) may rarely occur during VPA therapy. Structural abnormalities within neurons are postulated as one of the reasons for VE. The aim of this study was to assess the ultrastructure of neurons in the hippocampal cortex during the course of chronic application of VPA to rats. VPA was chronically administered to rats, intragastrically, once daily at a dose of 200 mg/kg b.w. for 1, 3, 6, 9 and 12 months. The samples of hippocampal cortex, after routine laboratory preparation, were examined by electron microscopy. The drug induced pronounced ultrastructural changes in the population of pyramidal neurons within the hippocampal cortex after 9 and 12 months of VPA administration. The most expressed abnormalities were observed within the mitochondria and manifested by fragmentation of crests and almost complete disappearance of intramitochondrial granules. Mitochondria of numerous neurons resembled large vacuolar structures. Widening, shortening and irregular distribution of rough endoplasmic reticulum was also found. A characteristic feature of damaged neurocytes in the last two phases of the experiment was the disintegration of nuclear chromatin and the presence of numerous lipofuscin deposits within hyaloplasm. These cells assumed the look of “dark neurons” and presented the ultrastructural features of apoptosis and necrosis. Our results indicate that long-term VPA administration to rats leads to aponecrosis of hippocampal neurons. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 31–37)
Abstract
Valproate (VPA) is a widely used antiepileptic drug. A serious neurological-outcome defined as valproate encephalopathy (VE) may rarely occur during VPA therapy. Structural abnormalities within neurons are postulated as one of the reasons for VE. The aim of this study was to assess the ultrastructure of neurons in the hippocampal cortex during the course of chronic application of VPA to rats. VPA was chronically administered to rats, intragastrically, once daily at a dose of 200 mg/kg b.w. for 1, 3, 6, 9 and 12 months. The samples of hippocampal cortex, after routine laboratory preparation, were examined by electron microscopy. The drug induced pronounced ultrastructural changes in the population of pyramidal neurons within the hippocampal cortex after 9 and 12 months of VPA administration. The most expressed abnormalities were observed within the mitochondria and manifested by fragmentation of crests and almost complete disappearance of intramitochondrial granules. Mitochondria of numerous neurons resembled large vacuolar structures. Widening, shortening and irregular distribution of rough endoplasmic reticulum was also found. A characteristic feature of damaged neurocytes in the last two phases of the experiment was the disintegration of nuclear chromatin and the presence of numerous lipofuscin deposits within hyaloplasm. These cells assumed the look of “dark neurons” and presented the ultrastructural features of apoptosis and necrosis. Our results indicate that long-term VPA administration to rats leads to aponecrosis of hippocampal neurons. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 31–37)
Keywords
valproate encephalopathy; hippocampus; ultrastructure; neurons; mitochondria; RER; aponecrosis
About this articleTitle
Ultrastructural study of hippocampal cortex neurons in an experimental model of valproate encephalopathy
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
31-37
Published online
2013-04-24
Page views
1443
Article views/downloads
1777
DOI
10.5603/FHC.2013.005
Bibliographic record
Folia Histochem Cytobiol 2013;51(1):31-37.
Keywords
valproate encephalopathy
hippocampus
ultrastructure
neurons
mitochondria
RER
aponecrosis
Authors
Krzysztof Sendrowski
Wojciech Sobaniec
Piotr Sobaniec
Maria E. Sobaniec-Lotowska
