| Description |
Author Affiliation: Zhang D ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Yan H ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Li H ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Hao S ( Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing 210093, Jiangsu Province, and.); Zhuang Z ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Liu M ( the Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province, China.); Sun Q ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Yang Y ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Zhou M ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province.); Li K ( Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing 210093, Jiangsu Province, and likuanyu@nju.edu.cn.); Hang C ( From the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Rd., Nanjing 210002, Jiangsu Province, the Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Rd., Nanjing 2100) |
| Abstract |
Accumulating evidence suggests that activation of mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking proapoptotic and proinflammatory cellular signaling. Here we evaluate the role of TGFß-activated kinase 1 (TAK1), a critical regulator of the NF-κB and MAPK pathways, in early brain injury following SAH. Although the expression level of TAK1 did not present significant alternation in the basal temporal lobe after SAH, the expression of phosphorylated TAK1 (Thr-187, p-TAK1) showed a substantial increase 24 h post-SAH. Intracerebroventricular injection of a selective TAK1 inhibitor (10 min post-SAH), 5Z-7-oxozeaenol (OZ), significantly reduced the levels of TAK1 and p-TAK1 at 24 h post-SAH. Involvement of MAPKs and NF-κB signaling pathways was revealed that OZ inhibited SAH-induced phosphorylation of p38 and JNK, the nuclear translocation of NF-κB p65, and degradation of IκB . Furthermore, OZ administration diminished the SAH-induced apoptosis and EBI. As a result, neurological deficits caused by SAH were reversed. Our findings suggest that TAK1 inhibition confers marked neuroprotection against EBI following SAH. Therefore, TAK1 might be a promising new molecular target for the treatment of SAH. |
