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01-04-2009 | Basic Neurosciences, Genetics and Immunology - Original Article

Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats

Authors: S. Matsuda, M. Umeda, H. Uchida, H. Kato, Tsutomu Araki

Published in: Journal of Neural Transmission | Issue 4/2009

Abstract

Cumulative evidence demonstrates that apoptosis caused by oxidative stress plays a key role in neuronal cell death after transient focal cerebral ischemia. In this study, we investigated exactly the immunohistochemical alterations of neuronal nuclei (NeuN), Cu/Zn-SOD (superoxide dismutase), Mn-SOD, 4-hydroxy-2-nonenal (HNE), and single strand DNA (ssDNA) in the striatum from 3 h up to 15 days after transient focal cerebral ischemia in rats under the same conditions. A conspicuous decrease of NeuN immunoreactive neurons was observed in the ipsilateral striatum from 3 h up to 15 days after focal ischemia. For Cu/Zn-SOD, Mn-SOD and HNE immunostainings, the alteration of Cu/Zn-SOD and HNE immunoreactivity was more pronounced than that of Mn-SOD immunoreactivity in the shrunken or atrophic neurons of ipsilateral striatum 3 h after focal ischemia. Thereafter, a significant increase of HNE immunoreactivity was observed in the shrunken or atrophic neurons of ipsilateral striatum up to 15 days after focal ischemia. In contrast, a significant decrease of Cu/Zn-SOD immunoreactivity was found in the ipsilateral striatum from 3 up to 15 days after focal ischemia. On the other hand, a significant increase of Mn-SOD immunereactivity was observed in the ipsilateral striatum from 1 up to 7 days after focal ischemia. In addition, our Western blot analysis also showed a significant increase of Cu/Zn-SOD and Mn-SOD in the ipsilateral striatum 1 day after focal ischemia, as compared to sham-operated group. In contrast, a significant increase in the number of ssDNA immunoreactive apoptotic neurons was observed in the ipsilateral striatum from 3 h to 3 days after focal cerebral ischemia. The present results also suggest that increased reactive oxygen species (ROS) production during reperfusion may contribute to the induction of the alteration of lipid peroxidation and could thereby lead to apoptosis in neurons of the ipsilateral striatum after transient focal ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Furthermore, our findings demonstrate that the lipid peroxidation against mitochondrial membrane may contribute to apoptosis of striatal neurons after transient focal ischemia. Thus our findings demonstrate that the protection of lipid peroxidation against mitochondrial membrane may offer a novel therapeutic strategy for brain stroke in humans.

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Title: Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats
Authors: S. Matsuda
M. Umeda
H. Uchida
H. Kato
Tsutomu Araki
Publication date: 01-04-2009
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 4/2009
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-009-0194-0

At a glance: The STEP trials

Springer Medicine

Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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