Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Hubei, China.
PLoS One. 2018 Feb 15;13(2):e0193037. doi: 10.1371/journal.pone.0193037. eCollection 2018.
Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.
Notch 信号通路参与许多生理和病理过程。γ-分泌酶抑制剂 DAPT 抑制 Notch 信号通路,并促进脑缺血后的神经再生。然而,DAPT 对急性颅脑损伤的神经保护作用尚不清楚。在本研究中,我们建立了大鼠急性颅脑损伤模型,发现随着损伤程度的增加,Notch 及其下游蛋白 Hes1 和 Hes5 的表达逐渐增加。给予 DAPT 后,Notch、Hes1 和 Hes5 的表达受到抑制,细胞凋亡和氧化应激减少,神经功能和认知功能改善。这些结果表明,Notch 信号通路可作为评估创伤性脑损伤严重程度的指标。Notch 抑制剂 DAPT 可减轻急性颅脑损伤后的氧化应激和细胞凋亡,是治疗急性颅脑损伤的潜在药物。