Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice.
Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice.
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DOI：
10.3389/fneur.2017.00363
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发表时间：
2017
影响因子：
3.4
通讯作者：
Candelario-Jalil E
中科院分区：
文献类型：
--
作者：
DeMars KM;Pacheco SC;Yang C;Siwarski DM;Candelario-Jalil E
Janus kinase 3 (JAK3) is associated with the common gamma chain of several interleukin (IL) receptors essential to inflammatory signaling. To study the potential role of JAK3 in stroke-induced neuroinflammation, we subjected mice to permanent middle cerebral artery occlusion and investigated the effects of JAK3 inhibition with decernotinib (VX-509) on infarct size, behavior, and levels of several inflammatory mediators. Results from our double immunofluorescence staining showed JAK3 expression on neurons, endothelial cells, and microglia/macrophages in the ischemic mouse brain (n = 3). We found for the first time that total and phosphorylated/activated JAK3 are dramatically increased after stroke in the ipsilateral hemisphere (**P < 0.01; n = 5–13/group) in addition to increased IL-21 expression after stroke (**P < 0.01; n = 5–7/group). However, inhibition of JAK3 confirmed by reduced phosphorylation of its activation loop at tyrosine residues 980/981 does not reduce infarct volume measured at 48 h after stroke (n = 6–10/group) nor does it alter behavioral outcomes sensitive to neurological deficits or stroke-induced neuroinflammatory response (n = 9–10/group). These results do not support a detrimental role for JAK3 in acute neuroinflammation following permanent focal cerebral ischemia. The functional role of increased JAK3 activation after stroke remains to be further investigated.
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影响因子：
12.8
作者：
Oh, Young-Bin;Ahn, Min;Lee, Sang-Myeong;Koh, Hyoung-Won;Lee, Sun-Hwa;Kim, Suhn Hee;Park, Byung-Hyun
通讯作者：
Park, Byung-Hyun
DOI：
10.4049/jimmunol.1203084
发表时间：
2013-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wang H;Brown J;Gao S;Liang S;Jotwani R;Zhou H;Suttles J;Scott DA;Lamont RJ
通讯作者：
Lamont RJ
影响因子：
8.3
作者：
Kinouchi, Tomoya;Kitazato, Keiko T.;Nagahiro, Shinji
通讯作者：
Nagahiro, Shinji
影响因子：
8.3
作者：
Pantano, P;Caramia, F;von Kummer, R
通讯作者：
von Kummer, R
影响因子：
8.3
作者：
Fisher M;Feuerstein G;Howells DW;Hurn PD;Kent TA;Savitz SI;Lo EH;STAIR Group
通讯作者：
STAIR Group