title: Temporal analysis of blood-brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke.
abstract: Blood-brain barrier (BBB) disruption plays an important role in pathophysiological progress of ischemic stroke. However, our knowledge of the dynamic change of BBB permeability and its mechanism remains limited. In the current study, we used a non-human primate (NHP) MCAO model and a serial CSF sampling method that allowed us to determine the dynamic change of BBB permeability by calculating the CSF/serum albumin ratio (AR). We showed that AR increased rapidly and significantly after ischemia, and the fold increase of AR is highly correlated with the infarction size during the subacute phase. Moreover, we determined the temporal change of MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in CSF and serum. Each MMP and TIMP showed different change patterns when comparing their values in CSF and serum. Based on the longitudinal dataset, we showed that the fold increase of MMP-9 in serum and CSF are both correlated to infarction size. Among the measured MMPs and TIMPs, only MMP-2, MMP-13, and TIMP-2 in CSF correlated with AR to some extent. Our data suggest there is no single MMP or TIMP fully responsible for BBB breakdown, which is regulated by a much more complicated signal network and further investigations of the mechanisms are needed.
authors.affiliation: 1 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2 Department of Neurointervention, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Fan
authors.affiliation: 3 Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zeng
authors.affiliation: 4 Department of Medical Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 5 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China.
authors.forename: Yinbing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 5 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 6 Department of Interventional therapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: He
authors.initials: H
authors.lastname: Jiao
authors.affiliation: 1 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 1 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: 7 Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: 5 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: 5 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xiao
authors.affiliation: 8 National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.|5 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000201:enzymology*; D002946:Cisterna Magna / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D012709:Serum Albumin; D020782:Matrix Metalloproteinases
keywords: Blood–brain barrier; brain ischemia; cerebrospinal fluid; matrix proteins