Anti-inflammatory treatment in oxygen-glucose-deprived hippocampal slice cultures is neuroprotective and associated with reduced cell proliferation and intact neurogenesis
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.
机构:
Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Arai, K
;
Nishiyama, N
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Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Nishiyama, N
;
Matsuki, N
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Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Matsuki, N
;
Ikegaya, Y
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Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
机构:
Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Arai, K
;
Nishiyama, N
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Nishiyama, N
;
Matsuki, N
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan
Matsuki, N
;
Ikegaya, Y
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Chem Pharmacol Lab, Bunkyo Ku, Tokyo 1130033, Japan