Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.
Hong-Mei ZhangPei LiuCheng JiangXiao-Qing JinRui-Ning LiuShun-Qing LiYan ZhaoPublished in: PloS one (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.
Keyphrases
- oxidative stress
- liver failure
- antiplatelet therapy
- cerebral ischemia
- signaling pathway
- poor prognosis
- respiratory failure
- traumatic brain injury
- drug induced
- cell proliferation
- induced apoptosis
- aortic dissection
- endoplasmic reticulum stress
- epithelial mesenchymal transition
- blood brain barrier
- stem cells
- pi k akt
- long non coding rna
- hepatitis b virus
- acute coronary syndrome
- cell death
- risk assessment
- cell cycle arrest
- brain injury
- diabetic rats
- atrial fibrillation
- amino acid
- small molecule
- heat shock protein
- heat stress