Author/Authors :
Tian, Jia-qi Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China , Zheng, Jia-jun Department of Neurosurgery - Huashan Hospital - Fudan University, Shanghai, China , Hao, Xiao-zhu Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China , Yin, Le-kang Department of Radiology - Shanghai Chest hospital - Shanghai Jiao Tong University, China , Zhang, Xiao-xue Department of Radiotherapy - Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China , Li, Chan-chan Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China , Feng, Xiao-yuan Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China , Jiang, Min Institutes of Science and State Key Laboratory of Medical Neurobiology - Fudan University, Shanghai, China , Sun, Hua-ping Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China , Zheng, Kang Department of Neurosurgery - Huashan Hospital - Fudan University, Shanghai, China , Yang, Yan-mei Department of Radiology - Huashan Hospital - Fudan University, Shanghai, China
Abstract :
Objective. The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the
γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study
was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance
imaging (MRI). Methods. Sprague-Dawley rats (n = 40) were subjected to 90 minutes of transient middle cerebral artery (MCA)
occlusion and treated with PBS (n = 20) or DAPT (n = 20) at 72 hours after the onset of ischemia. MRI measurements including
T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at
24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained
at each time point after MRI scans. Results. SWI showed that DAPT treatment significantly enhanced angiogenesis in the
ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with
increases in vascular density confirmed by histology. Conclusion. Treatment of ischemic stroke with DAPT significantly
augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be
dynamically monitored and evaluated by MRI.
Keywords :
Dynamic Evaluation , Notch Signaling-Mediated , Angiogenesis , Ischemic Rats , Magnetic Resonance Imaging
