title: Downregulating hypoxia-inducible factor-1α expression with perfluorooctyl-bromide nanoparticles reduces early brain injury following experimental subarachnoid hemorrhage in rats.
abstract: The aim of the present study was to investigate the effects of perfluorooctyl-bromide (PFOB) nanoparticles on hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target genes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Healthy male Sprague Dawley rats (n=100) were randomly divided into five groups: Sham, SAH, SAH + vehicle, SAH + 5 mg/kg PFOB and SAH + 10 mg/kg PFOB. A rat model of SAH was created by endovascular perforation, and PFOB treatment (5 mg/kg or 10 mg/kg injected into the caudal vein) was initiated 1 h after SAH. All rats were subsequently sacrificed 24 h after surgery. Treatment with PFOB significantly alleviated EBI (including neurological dysfunction, brain edema, blood-brain barrier disruption (BBB), and neural cell apoptosis). In addition, it also suppressed the expression of HIF-1α, vascular endothelial growth factor (VEGF) and BNIP3 in the rat hippocampus. The effects of 10 g/kg PFOB were found to be more obvious than those of 5 g/kg PFOB. Our work demonstrated that PFOB treatment alleviated EBI after SAH, potentially through downregulation of the expression of HIF-1α and its target genes, which led to reduced cell apoptosis, BBB disruption and brain edema.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Boston 02115, Massachusetts, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
keywords: Early brain injury; hypoxia-inducible factor 1 alpha; perfluorooctyl-bromide; subarachnoid hemorrhage; vascular endothelial growth factor