AUTHOR=DeMars Kelly M. , Pacheco Sean C. , Yang Changjun , Siwarski David M. , Candelario-Jalil Eduardo TITLE=Selective Inhibition of Janus Kinase 3 Has No Impact on Infarct Size or Neurobehavioral Outcomes in Permanent Ischemic Stroke in Mice JOURNAL=Frontiers in Neurology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00363 DOI=10.3389/fneur.2017.00363 ISSN=1664-2295 ABSTRACT=

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.