JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
Zheng, Dai, Han, Hong, Jia, Mo, Lv, Tang, Fu, Geng (2020) JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke J Cell Physiol (IF: 5.6) 235(3) 2792-2799
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Abstract
C-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood. In this work, male rats were treated with JNK-IN-8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot-fault test (FFT), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels were assessed. We found that JNK-IN-8-treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK-IN-8 also played anti-inflammatory roles as indicated through decreased activation of microglia and decreased IL-6, IL-1β, and TNF-α expression. Furthermore, JNK-IN-8 suppressed the activation of JNK and nuclear factor-κB (NF-κB) signaling as indicated by the decreased level of phosphorylated-JNK and p65. All data demonstrate that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury.© 2019 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916328http://www.ncbi.nlm.nih.gov/pubmed/31541462
http://dx.doi.org/10.1002/jcp.29183
