title: Cyclosporine A alleviated matrix metalloproteinase 9 associated blood-brain barrier disruption after subarachnoid hemorrhage in mice.
abstract: The aim of this study was to investigate whether Cyclosporine A (CsA) attenuates early brain injury by alleviating matrix metalloproteinase 9 (MMP-9) associated blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in C57B6J mice. Dosages of 5mg/kg, 10mg/kg and 15mg/kg CsA were evaluated for effects on neurological score, brain water content, Evans blue extravasation and fluorescence, P-p65, MMP-9 and BBB components' alterations after SAH. We found that CsA 15mg/kg is effective in attenuating BBB disruption, lowering edema, and improving neurological outcomes. In addition, Collagen IV, ZO-1, Occludin and Claudin 5 expressions in ipsilateral/left hemisphere were downregulated after SAH, but increased after CsA treatment. Our results suggest that CsA exert a neuroprotective role in SAH pathophysiology, possibly by alleviating MMP-9 associated BBB disruption.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Pan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hengli
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qu
authors.affiliation: Neuroscience Research Center, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China. Electronic address: fenghua8888@vip.163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China. Electronic address: yujiechen6886@foxmail.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D001929:Brain Edema / Q000517:prevention & control; D062507:Claudin-5 / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D062793:Occludin / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062507:Claudin-5; C491511:Cldn5 protein, mouse; D018696:Neuroprotective Agents; D062793:Occludin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D016572:Cyclosporine; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Blood-brain barrier; Cyclosporine A; Early brain injury; Matrix metalloproteinase 9; Subarachnoid hemorrhage