title: Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO.
abstract: The blood brain barrier (BBB) could be damaged within the thrombolytic time window and is considered to be a precursor to hemorrhagic transformation during reperfusion. Although we have recently reported the association between BBB damage and tissue injury within the thrombolytic time window, our knowledge about this early BBB damage is limited. In this study, rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with Evan's blue as a tracer to detect BBB damage. Rat brain was sliced into 10 consecutive sections and with TTC staining, a macro and full view of the spatial distribution of BBB damage and tissue injury could be clearly seen in the same group of animals. After 2-h MCAO, tissue injury started from 2nd slice and the BBB leakage started from the 5th slice, of note, there is no colocalization between BBB damage and tissue injury. Fluoro Jade B was employed to explore the localization of neuronal degeneration, and our results showed that 2-h MCAO produced greater number of positive cells in ischemic cortex and dorsal striatum than other areas. More important, 2-h MCAO induced occludin but not claudin-5 degradation in the ischemic hemisphere and pretreatment with MMP inhibitor GM6001 significantly reduced occludin degradation as well as BBB damage detected by IgG leakage. Taken together, our findings demonstrated a "mismatch" between ischemic tissue injury and BBB leakage and a differential degradation of occludin and claudin-5 by MMP-2 after 2-h MCAO.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Central Laboratory, Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital Shenzhen, 518035, China.
authors.forename: Wenlan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China. Electronic address: xinchunjin@gmail.com.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Jin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D005070:Evans Blue / Q000008:administration & dosage / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005070:Evans Blue
keywords: Blood brain barrier; Cerebral ischemia; Injury; MMP-2; Tight junction protein