title: Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage.
abstract: Apolipoprotein E (ApoE)-mimetic peptides have been demonstrated to be beneficial in secondary brain injury following experimental subarachnoid hemorrhage (SAH). However, the molecular mechanisms underlying these benefits in SAH models have not been clearly identified. This study investigated whether an ApoE-mimetic peptide affords neuroprotection in early brain injury (EBI) following SAH by attenuating BBB disruption. SAH was induced by an endovascular perforation in young, healthy, male wild-type (WT) C57BL/6J mice. Multiple techniques, including MRI with T2-weighted imaging,18FDG PET-CT scanning and histological studies, were used to examine BBB integrity and neurological dysfunction in EBI following SAH. We found that SAH induced a significant increase of BBB permeability and neuron apoptosis, whereas ApoE-mimetic peptide treatment significantly reduced the degradation of tight junction proteins and endothelial cell apoptosis. These effects reduced brain edema and neuron apoptosis, increased cerebral glucose uptake, and improved neurological functions. Further investigation revealed that the ApoE-mimetic peptide inhibited the proinflammatory activators of MMP-9, including CypA, NF-κB, IL-6, TNF-α, and IL-1β, thereby ameliorating BBB disruption at the acute stage of SAH. Together, these data indicate that ApoE-mimetic peptide may be a novel and promising therapeutic strategy for EBI amelioration after SAH that are worthy of further study.
authors: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Jinwei
authors: J
authors: Pang
authors: Department of Clinical Medicine, Medical College of Soochow University, Soochow, Jiangsu, China.
authors: Yitian
authors: Y
authors: Chen
authors: Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Li
authors: L
authors: Kuai
authors: Department of Vasculocardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Ping
authors: P
authors: Yang
authors: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Jianhua
authors: J
authors: Peng
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Yue
authors: Y
authors: Wu
authors: Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Yue
authors: Y
authors: Chen
authors: Duke University Medical Center, Medicine, Durham, NC, USA.
authors: Michael P
authors: MP
authors: Vitek
authors: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
authors: Ligang
authors: L
authors: Chen
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Xiaochuan
authors: X
authors: Sun
authors: Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. jiangy0122@gmail.com.
authors: Yong
authors: 0000-0002-4516-176X
authors: Y
authors: Jiang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*
chemical_list: D001057:Apolipoproteins E; D016328:NF-kappa B; D018696:Neuroprotective Agents
keywords: ApoE-mimetic peptide; Apoptosis; Blood-brain barrier; Early brain injury; Subarachnoid hemorrhage