open access

Vol 51, No 1 (2013)
Original paper
Submitted: 2013-04-28
Accepted: 2013-04-28
Published online: 2013-04-24
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Ultrastructural study of hippocampal cortex neurons in an experimental model of valproate encephalopathy

Krzysztof Sendrowski, Wojciech Sobaniec, Piotr Sobaniec, Maria E. Sobaniec-Lotowska
DOI: 10.5603/FHC.2013.005
·
Folia Histochem Cytobiol 2013;51(1):31-37.

open access

Vol 51, No 1 (2013)
ORIGINAL PAPERS
Submitted: 2013-04-28
Accepted: 2013-04-28
Published online: 2013-04-24

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)

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Keywords

valproate encephalopathy; hippocampus; ultrastructure; neurons; mitochondria; RER; aponecrosis

About this article
Title

Ultrastructural study of hippocampal cortex neurons in an experimental model of valproate encephalopathy

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 51, No 1 (2013)

Article type

Original paper

Pages

31-37

Published online

2013-04-24

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

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