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Neuronal and nonneuronal COX‐2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge
Author(s) -
An Ying,
Belevych Natalya,
Wang Yufen,
Zhang Hao,
Herschman Harvey,
Chen Qun,
Quan Ning
Publication year - 2014
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23317
Subject(s) - neuroprotection , neurotoxicity , lesion , microglia , neuroscience , biology , pharmacology , medicine , immunology , inflammation , pathology , toxicity
Treating acute brain injuries with COX‐2 inhibitors can produce both neuroprotective and neurotoxic effects. This study investigated the role of COX‐2 in modulating acute brain injury induced by excitotoxic neural damage. Intrastriatal injection of excitotoxin ( RS )‐(tetrazole‐5yl) glycine elicited COX‐2 expression in two distinct groups of cells. cortical neurons surrounding the lesion and vascular cells in the lesion core. The vascular COX‐2 was expressed in two cell types, endothelial cells and monocytes. Selective deletion of COX‐2 in vascular cells in Tie2Cre Cox‐2 flox/flox mice did not affect the induction of COX‐2 in neurons after the excitotoxin injection but resulted in increased lesion volume, indicating a neuroprotective role for the COX‐2 expressed in the vascular cells. Selective deletion of monocyte COX‐2 in LysMCre Cox‐2 flox/flox mice did not reduce COX‐2‐dependent neuroprotection, suggesting that endothelial COX‐2 is sufficient to confer neuroprotection. Pharmacological inhibition of COX‐2 activity in Tie2Cre Cox‐2 flox/flox mice reduced lesion volume, indicating a neurotoxic role for the COX‐2 expressed in neurons. Furthermore, COX‐2‐dependent neurotoxicity was mediated, at least in part, via the activation of the EP1 receptor. These results show that Cox‐2 expression induced in different cell types can confer opposite effects. © 2013 Wiley Periodicals, Inc.