Glucocorticoids increase excitotoxic injury and inflammation in the hippocampus of adult male rats.

Abstract:

BACKGROUND/AIMS: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.

journal_name

Neuroendocrinology

journal_title

Neuroendocrinology

authors

Sorrells SF,Munhoz CD,Manley NC,Yen S,Sapolsky RM

doi

10.1159/000367849

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

129-40

issue

2-3

eissn

0028-3835

issn

1423-0194

pii

000367849

journal_volume

100

pub_type

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