Research Papers: Pathology:
Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity
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Jinwei Pang1,*, Yue Wu2,*, Jianhua Peng1, Ping Yang3, Li Kuai4, Xinghu Qin1, Fang Cao5, Xiaochuan Sun2, Ligang Chen1, Michael P. Vitek6 and Yong Jiang1
1 Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2 Departement of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
3 Department of Vasculocardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
4 Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
5 Department of Neurovascular Disease, The Affiliated Hospital of Zunyi Medical College, Zunyi, China
6 Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, United States
* co-first authors
Yong Jiang, email:
Keywords: subarachnoid hemorrhage, Apolipoprotein E, early brain injury, blood-brain barrier, neuroinflamamation, Pathology Section
Received: April 23, 2016 Accepted: July 10, 2016 Published: July 24, 2016
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.
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