title: Glucocorticoids increase excitotoxic injury and inflammation in the hippocampus of adult male rats.
abstract: OBJECTIVE
  Stress exacerbates neuron loss in many CNS injuries via the actions of adrenal glucocorticoid (GC) hormones. For some injuries, this GC endangerment of neurons is accompanied by greater immune cell activation in the CNS, a surprising outcome given the potent immunosuppressive properties of GCs.
  
  
  METHODS
  To determine whether the effects of GCs on inflammation contribute to neuron death or result from it, we tested whether nonsteroidal anti-inflammatory drugs could protect neurons from GCs during kainic acid excitotoxicity in adrenalectomized male rats. We next measured GC effects on (1) chemokine production (CCL2 and CINC-1), (2) signals that suppress immune activation (CX3CL1, CD22, CD200, and TGF-β), and (3) NF-κB activity.
  
  
  RESULTS
  Concurrent treatment with minocycline, but not indomethacin, prevented GC endangerment. GCs did not substantially affect CCL2, CINC-1, or baseline NF-κB activity, but they did suppress CX3CL1, CX3CR1, and CD22 expression in the hippocampus - factors that normally restrain inflammatory responses.
  
  
  CONCLUSIONS
  These findings demonstrate that cellular inflammation is not necessarily suppressed by GCs in the injured hippocampus; instead, GCs may worsen hippocampal neuron death, at least in part by increasing the neurotoxicity of CNS inflammation.
authors.affiliation: Department of Biology, Stanford University, Stanford, Calif., USA.
authors.forename: Shawn F
authors.initials: SF
authors.lastname: Sorrells
authors.forename: Carolina D
authors.initials: CD
authors.lastname: Munhoz
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Manley
authors.forename: Sandra
authors.initials: S
authors.lastname: Yen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sapolsky
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005938:Glucocorticoids / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D018690:Excitatory Amino Acid Agonists; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D008911:Minocycline; D007608:Kainic Acid; D007213:Indomethacin