1. The neurovascular protective effect of alogliptin in murine MCAO model and brain endothelial cells
- Author
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Xin-jian Lu, Xiong-fei Zhao, Ai-hong Guo, Xiao-fang Han, Feng-li Hao, Zhi-ru Zhao, and Xiao-li Wang
- Subjects
Male ,0301 basic medicine ,Neurovascular protection ,Vascular permeability ,RM1-950 ,Matrix metalloproteinase ,Pharmacology ,Occludin ,Neuroprotection ,Brain Ischemia ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Piperidines ,In vivo ,MCAO model ,medicine ,Animals ,Humans ,Uracil ,Alogliptin ,Cells, Cultured ,Cerebral infarction ,business.industry ,Brain ,Endothelial Cells ,Infarction, Middle Cerebral Artery ,General Medicine ,Tissue inhibitor of metalloproteinase ,medicine.disease ,Mice, Inbred C57BL ,Stroke ,Neuroprotective Agents ,030104 developmental biology ,030220 oncology & carcinogenesis ,Zonula Occludens-1 Protein ,Therapeutics. Pharmacology ,Brain endothelial cells ,business - Abstract
Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.
- Published
- 2019
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