title: Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse.
abstract: Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zan
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.affiliation: Department of Neurology, the Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Diabetes Center, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China. Electronic address: guiyuncui@foxmail.com.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011983:Receptors, Purinergic
keywords: Caspase-3; Ischemic stroke; NLRP3 inflammasome; Neuronal apoptosis; P2X7 receptor