Neuronal and nonneuronal COX-2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge.
Neuronal and nonneuronal COX-2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge.
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DOI：
10.1002/jnr.23317
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发表时间：
2014-04
影响因子：
4.2
通讯作者：
Quan, Ning
中科院分区：
文献类型：
--
作者：
An, Ying;Belevych, Natalya;Wang, Yufen;Zhang, Hao;Herschman, Harvey;Chen, Qun;Quan, Ning
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-2flox/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-2flox/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-2flox/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.
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影响因子：
3.9
作者：
Hardingham GE
通讯作者：
Hardingham GE
影响因子：
2.5
作者：
Hara, K;Kong, DL;Weinstein, PR
通讯作者：
Weinstein, PR
DOI：
10.1073/pnas.93.6.2317
发表时间：
1996-03-19
影响因子：
11.1
作者：
Kaufmann, WE;Worley, PF;Isakson, P
通讯作者：
Isakson, P
影响因子：
168.9
作者：
Chan, Francis K. L.;Lanas, Angel;Goldstein, Jay L.
通讯作者：
Goldstein, Jay L.
影响因子：
11.2
作者：
Cudkowicz, Merit E.;Shefner, Jeremy M.;Drachman, Daniel B.
通讯作者：
Drachman, Daniel B.