Morroniside promotes angiogenesis and further improves microvascular circulation after focal cerebral ischemia/reperfusion.
Preservation of cerebral microvascular functional integrity is crucial for protecting and repairing the brain after stroke. Our previous study demonstrated that morroniside promoted angiogenesis 7days after stroke. The current study aimed to further evaluate the long-term effects of morroniside on angiogenesis and to examine whether angiogenesis induced by morroniside could improve blood flow velocity. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO), and morroniside was then administered once per day at a dose of 270mg/kg. New vessel formation and the expression of ephrinB2/VEGFR2 signaling pathway components were examined 14days after MCAO to examine angiogenesis and the associated mechanisms. The dynamics of regional cerebral blood flow (rCBF) and the number of vessels of the leptomeningeal anastomoses were analyzed to characterize microvascular circulation 3days after MCAO. We demonstrated that morroniside promoted angiogenesis by regulating the ephrinB2/VEGFR2 signaling pathway 14days post-ischemia. By 3days post-ischemia, morroniside improved rCBF and increased the number of vessels of the leptomeningeal anastomoses. Moreover, morroniside decreased the infarct volume and improved neurological function 14days after MCAO. Our findings suggest that morroniside promoted long-term angiogenesis, thereby improving microvascular circulation and neurological function. It suggested that the angiogenic mechanism of morroniside might be mediated by the ephrinB2/VEGFR2 signaling pathway.
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Tingting
T
Liu
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Benxu
B
Xiang
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Deyu
D
Guo
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Fangling
F
Sun
Department of Pharmacy, HeBei North University, Zhangjiakou 075000, Hebei Province, PR China.
Renping
R
Wei
Department of Life Science, Beijing Institute of Technology University, Beijing 100081, PR China.
Guoxing
G
Zhang
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Houxi
H
Ai
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Xin
X
Tian
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Zixin
Z
Zhu
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Wenrong
W
Zheng
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China.
Yufeng
Y
Wang
Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing 100053, PR China; Beijing Institute for Brain Disorders, Beijing 100069, PR China. Electronic address: lzwwang@163.com.
Wen
W
Wang
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D036388:Ephrin-B2 / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology*; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D036388:Ephrin-B2; D006027:Glycosides; C488401:morroniside; C000602029:Kdr protein, rat; D040301:Vascular Endothelial Growth Factor Receptor-2
Angiogenesis; Cerebral blood flow; EphrinB2/VEGFR2 signaling; Ischemic stroke; Morroniside