title: Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity.
abstract: Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential role of APOE in EBI post-SAH. Multiple techniques were used to determine the early BBB disruption in EBI post-SAH in a murine model using wild-type (WT) and Apoe-/- (KO) mice. Progressive BBB disruption (Evans blue extravasation and T2 hyperintensity in magnetic resonance imaging) was observed before the peak of endogenous APOE expression elevation at 48h after SAH. Moreover, Apoe-/- mice exhibited more severe BBB disruption charcteristics after SAH than WT mice, including higher levels of Evans blue and IgG extravasation, T2 hyperintensity in magnetic resonance imaging, tight junction proteins degradation and endothelial cells death. Mechanistically, we found that APOE restores the BBB integrity in the acute stage after SAH via the cyclophilin A (CypA)-NF-κB-proinflammatory cytokines-MMP-9 signalling pathway. Consequently, although early BBB disruption causes neurological dysfunctions after SAH, we capture a different aspect of the effects of APOE on EBI after SAH that previous studies had overlooked and open up the idea of BBB disruption as a target of APOE-based therapy for EBI amelioration research in the future.
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Pang
authors.affiliation: Departement of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Vasculocardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Kuai
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Xinghu
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Neurovascular Disease, The Affiliated Hospital of Zunyi Medical College, Zunyi, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: Departement of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000473:pathology* / Q000648:ultrastructure; D001929:Brain Edema / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology*; D021984:Cyclophilin A / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D019108:Tight Junctions / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D016328:NF-kappa B; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D021984:Cyclophilin A
keywords: Apolipoprotein E; Pathology Section; blood-brain barrier; early brain injury; neuroinflamamation; subarachnoid hemorrhage