Inflammatory blockade restores adult hippocampal neurogenesis.
Cranial radiation therapy causes a progressive decline in cognitive function that is linked to impaired neurogenesis. Chronic inflammation accompanies radiation injury, suggesting that inflammatory processes may contribute to neural stem cell dysfunction. Here, we show that neuroinflammation alone inhibits neurogenesis and that inflammatory blockade with indomethacin, a common nonsteroidal anti-inflammatory drug, restores neurogenesis after endotoxin-induced inflammation and augments neurogenesis after cranial irradiation.
Monje
Michelle L
ML
Stanford University, Department of Neurosurgery, MSLS P309, Mail Code 5487, 1201 Welch Road, Stanford, CA 94305-5487, USA.
Toda
Hiroki
H
Palmer
Theo D
TD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000502:physiology*; D008940:Mitotic Index; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D011916:Rats, Inbred F344; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines; C494200:Il6st protein, mouse; C494201:Il6st protein, rat; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D007213:Indomethacin