Anti-inflammatory treatment in oxygen-glucose-deprived hippocampal slice cultures is neuroprotective and associated with reduced cell proliferation and intact neurogenesis

被引:30
作者
Chechneva, Olga
Dinkel, Klaus
Cavaliere, Fabio
Martinez-Sanchez, Monica
Reymann, Klaus G.
机构
[1] Leibniz Inst Neurol, Project Grp Neurppharmacol, D-39118 Magdeburg, Germany
[2] FAN gGmbH, Res Inst Appl Neurosci, D-39120 Magdeburg, Germany
关键词
organotypic hippocampal slice cultures; oxygen-glucose deprivation; microglia; inflammation; cell damage; cell proliferation; neurogenesis; indomethacin; minocycline;
D O I
10.1016/j.nbd.2006.02.015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Increased neurogenesis in response to brain injury is considered a mechanism of regeneration after neuronal loss. Using organotypic hippocampal cultures (OHC), we investigated the interplay between neuronal damage (propidium iodide uptake), microglia activation (OX-42 immunohistochemistry), cell proliferation (bromodeoxyuridine incorporation), and neurogenesis (double labeling of bromodeoxyuridine with doublecortin or beta-III tubulin) after oxygen-glucose deprivation (OGD). We observed that microglia activation and upregulation of pro-inflammatory cytokines mRNA preceded neuronal loss and was followed by increased cell proliferation. Neurogenesis was inhibited 3 days after OGD in both neurogenic zones of the slice, the dentate gyros and the posterior periventricle (pPV). After 6 days, neurogenesis was restored and significantly increased in the pPV. Indomethacin or minocycline reduced the OGD-induced damage, proliferation, and increase of microglia. Both agents did not interfere with OGD-induced pPV neurogenesis. Our study shows for the first time that neuroprotection against OGD-induced damage in OHC by anti-inflammatory treatment is associated with intact neurogenesis. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:247 / 259
页数:13
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