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 gyrus 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.
Chechneva
Olga
O
Leibniz Institute for Neurobiology, Project Group Neuropharmacology, Magdeburg, Germany. mishelcon@hotmail.com
Dinkel
Klaus
K
Cavaliere
Fabio
F
Martinez-Sanchez
Monica
M
Reymann
Klaus G
KG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D000860:Hypoxia; D007213:Indomethacin / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D017931:DNA Primers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D005947:Glucose; D007213:Indomethacin