title: Morroniside improves microvascular functional integrity of the neurovascular unit after cerebral ischemia.
abstract: Treating the vascular elements within the neurovascular unit is essential for protecting and repairing the brain after stroke. Acute injury on endothelial systems results in the disruption of blood-brain barrier (BBB), while post-ischemic angiogenesis plays an important role in delayed functional recovery. Here, we considered alterations in microvessel integrity to be targets for brain recovery, and tested the natural compound morroniside as a therapeutic approach to restore the vascular elements of injured tissue in a rat model of focal cerebral ischemia. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) model, and morroniside was then administered intragastrically once a day at doses of 30, 90, and 270 mg/kg. BBB integrity and associated factors were analyzed to identify cerebrovascular permeability 3 days after MCAO. The recruitment of endothelial progenitor cells (EPCs), the expression of angiogenic factors and the new vessel formation in the peri-infarct cortex of rats were examined 7 days after MCAO to identify the angiogenesis. We demonstrated that at 3 days post-ischemia, morroniside preserved neurovascular unit function by ameliorating BBB injury. By 7 days post-ischemia, morroniside amplified angiogenesis, in part by enhancing endothelial progenitor cell proliferation and expression of angiogenic factors. Morever, the increase in the amount of vWF+ vessels induced by ischemia could be extended to 28 days after administration of morroniside, indicating the crucial role of morroniside in angiogenesis during the chronic phase. Taken together, our findings suggested that morroniside might offer a novel therapeutic approach for promoting microvascular integrity recovery and provide a thoroughly new direction for stroke therapy.
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Fang-Ling
authors: FL
authors: Sun
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Wen
authors: W
authors: Wang
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Hua
authors: H
authors: Cheng
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Ying
authors: Y
authors: Wang
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Lei
authors: L
authors: Li
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Jin-Long
authors: JL
authors: Xue
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Xiao-feng
authors: XF
authors: Wang
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Hou-Xi
authors: HX
authors: Ai
authors: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Jing-dong
authors: JD
authors: Xu
authors: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Xiao-Min
authors: XM
authors: Wang
authors: Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors: Xun-Ming
authors: XM
authors: Ji
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D006027:Glycosides; C488401:morroniside; D014841:von Willebrand Factor; D042787:Receptor, TIE-2; D020782:Matrix Metalloproteinases