title: Cerebral ischemia in the aged. Limited anti-inflammatory efficacy of the indomethacin treatment.
abstract: Ischemic stroke is a disease of aging and causes high mortality or long-term disability. Diminished neurological recovery after stroke in aged subjects is possibly associated with exaggerated non-specific inflammatory reaction. The focus of the present study was on neurobiological and behavioral differences between young and old rats modulated by indomethacin daily treatment starting at four hours after acute cerebral ischemia in animal model. Our results indicate age-independent positive consequences of non-specific inhibition of inflammation by indomethacin including increased NeuN-positive surviving neurons, reduced infarct volume and enhanced neuroprotective response of innate immune system evidenced by increased Iba1 and Anx3 immunoreactivities and moderately activated microglia in the peri-infarcted area. Quite relevantly, the efficacy of therapy with indomethacin was reduced. In the aged rats, specifically indomethacin is ineffective in inhibiting phagocytic activity, which is probably due failure of the aged brain to up-regulate the expression of several cytokines including TNFα and Cxcl4. At protein level, we observed no change of lysosomal ED1 immunoreactivity under treatment. Our study demonstrates the beneficial anti-inflammatory treatment with indomethacin. However, aging blunted the positive effect.
authors.affiliation: Department of Psychiatry, University of Medicine Rostock, Germany; aurel.popa-wagner@med.uni-rostock.de.
authors.forename: Raluca Elena
authors.initials: RE
authors.lastname: Sandu
authors.forename: Adriana
authors.initials: A
authors.lastname: Uzoni
authors.forename: Cristin
authors.initials: C
authors.lastname: Coman
authors.forename: Aurel
authors.initials: A
authors.lastname: Popa-Wagner
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D034961:Antigens, Nuclear / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C546339:Rbfox3 protein, rat; D007213:Indomethacin