PT  - JOURNAL ARTICLE
AU  - Hongli Tang
AU  - Qinxue Dai
AU  - Wandong Hong
AU  - Kunyuan Han
AU  - Danyun Jia
AU  - Yunchang Mo
AU  - Ya Lv
AU  - Hongxing Fu
AU  - Jianjian Zheng
AU  - Wujun Geng
TI  - JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
AID  - 10.1101/449496
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 449496
4099  - http://biorxiv.org/content/early/2018/10/21/449496.short
4100  - http://biorxiv.org/content/early/2018/10/21/449496.full
AB  - 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-1β, IL-6 and TNF-α) 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-1β and TNF-α. Furthermore, JNK-IN-8 suppressed the activation of JNK and subsequent activation of NF-κB 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-κB pathway after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.