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bioRxiv · 10.1101/449496

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke

Geng, W.·Tang, H.·Dai, Q.·Hong, W.·Han, K.·Jia, D.·Mo, Y.·Lv, Y.·Fu, H.·Zheng, J.
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Abstract

c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated in ischemia brain injury and plays an important role in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a specific JNK inhibitor) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the role of JNK-IN-8 in ischemic stroke and the underlying mechanisms of JNK-IN-8 involving neuroprotection remain poorly understood. In the present study, male rats were subjected to tMCAO (transient middle cerebral artery occlusion) followed by treatment with JNK-IN-8, and then the modified improved neurological function score (mNSS), the Foot-fault test and the level of inflammatory cytokines (IL-1{beta}, IL-6 and TNF-) were assessed. We found that JNK-IN-8-treated rats with MCAO exerted a significant improvement in spatial learning as measured by the improved mNSS, and showed sensorimotor functional recovery as measured by the Foot-fault test. JNK-IN-8 also exerted anti-inflammatory effects as indicated by decreased activation of microglia and the decreased expresson of IL-6, IL-1{beta} and TNF-. Furthermore, JNK-IN-8 suppressed the activation of JNK and subsequent activation of NF-{kappa}B signaling as indicated by the decreased level of phosphorylated JNK (p-JNK) and p65. These data suggest that JNK-IN-8 suppressed neuroinflammation and improved neurological function by inhibiting JNK/NF-{kappa}B pathway after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

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Geng, W., Tang, H., Dai, Q., Hong, W., Han, K., Jia, D., Mo, Y., Lv, Y., Fu, H., Zheng, J.. 2018-10-21. JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke. https://doi.org/10.1101/449496

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