Inflammatory blockade restores adult hippocampal neurogenesis

Science. 2003 Dec 5;302(5651):1760-5. doi: 10.1126/science.1088417. Epub 2003 Nov 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antigens, CD / metabolism
  • Apoptosis
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned
  • Cytokine Receptor gp130
  • Cytokines / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology
  • Dentate Gyrus / radiation effects
  • Female
  • Gamma Rays
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Hippocampus / radiation effects
  • In Situ Nick-End Labeling
  • Indomethacin / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / physiopathology*
  • Interleukin-6 / pharmacology
  • Interleukin-6 / physiology
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microglia / physiology*
  • Mitotic Index
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Rats
  • Rats, Inbred F344
  • Receptors, Interleukin-6 / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Stem Cells / physiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antigens, CD
  • Culture Media, Conditioned
  • Cytokines
  • Il6st protein, mouse
  • Il6st protein, rat
  • Interleukin-6
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • Recombinant Proteins
  • Cytokine Receptor gp130
  • Indomethacin