Activation of the Notch-1 signaling pathway may be involved in intracerebral hemorrhage-induced reactive astrogliosis in rats

• Published in: Journal of neurosurgery Vol. 129; no. 3; pp. 732 - 739
• Main Authors: Zhong, Jian-Hua, Zhou, Hua-Jun, Tang, Tao, Cui, Han-Jin, Yang, A-Li, Zhang, Qi-Mei, Zhou, Jing-Hua, Zhang, Qiang, Gong, Xun, Zhang, Zhao-Hui, Mei, Zhi-Gang
• Format: Journal Article
• Language: English
• Published: United States 01-09-2018
• Subjects: DAPT = N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester; intracerebral hemorrhage; ICH = intracerebral hemorrhage; Notch-1 signaling; reactive astrogliosis; glial scar; PCNA = proliferating cell nuclear antigen; NICD = Notch intracellular domain; AUR = asymmetrical use rate
• ISSN: 0022-3085; 1933-0693
• DOI: 10.3171/2016.11.JNS162121

OBJECTIVE Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH. METHODS ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[ N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats' brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively. RESULTS Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH. CONCLUSIONS Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.