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

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. All data demonstrate that c‐Jun N‐terminal kinase (JNK)‐IN‐8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/nuclear factor‐κB (NF‐κB) and is a promising agent for the prevention of ischemic brain injury.