c‑Jun N‑terminal kinase inhibition attenuates early brain injury induced neuronal apoptosis via decreasing p53 phosphorylation and mitochondrial apoptotic pathway activation in subarachnoid hemorrhage rats
Geng-Qiang Ling 1 , Xian-Feng Li 1 , Xu-Hui Lei 1 , Zhen-Yu Wang 1 , Dong-Ying Ma 1 , Yue-Na Wang 1 , Wei Ye 1 Affiliations
- PMID: 30431087
- PMCID: PMC6297759
- DOI: 10.3892/mmr.2018.9640
Free PMC article
Early brain injury (EBI)‑induced neuronal apoptosis is primarily responsible for the subsequent complications of aneurysmal subarachnoid hemorrhage (aSAH), which may increase the risk of mortality in patients with aSAH. c‑Jun N‑terminal kinase (JNK) has been demonstrated to be a promoter of EBI‑induced cell apoptosis, although the mechanism has yet to be fully elucidated. The present study aimed to explore whether the role of JNK1 is associated with tumor protein p53 (p53), which is one of the most important factor that triggers cell apoptosis. JNK1 expression was downregulated via in vivo small interfering RNA transfection in an aSAH rat model in order to assess differences in the behavior, survival times, morphology and genetics of the experimental animals. The results revealed that JNK1 inhibition improved the neurological scores and survival times of SAH rats by interrupting cascaded neuronal apoptosis. The interruption of EBI‑induced neuronal apoptosis may originate from a decrease in the level of p53 phosphorylation and deactivation of the downstream mitochondrial apoptotic pathway. Taken together, these results suggest that JNK1 may be a promising target for improving the prognosis of patients with aSAH.
Keywords: aneurysmal subarachnoid hemorrhage; early brain injury; apoptosis; c-Jun N-terminal kinase; tumor protein 53.