title: CD47 deficiency improves neurological outcomes of traumatic brain injury in mice.
abstract: CD47 is a receptor for signal-regulatory protein alpha (SIRPα) in self-recognition by the innate immune system, and a receptor of thrombospondin-1 (TSP-1) contributing to vascular impairment in response to stress. However, the roles of CD47 in traumatic brain injury (TBI) have not been investigated. In this study we aimed to test our hypothesis that CD47 mediates early neutrophil brain infiltration and late brain vascular remodeling after TBI. Mice were subjected to TBI using a controlled cortical impact (CCI) device. We examined early phase neutrophil infiltration, and late phase brain vessel density, pro-angiogenic markers VEGF and Ang-1 protein expression, neurological function deficits and lesion volumes for up to three weeks after TBI. Our results show that mice deficient in CD47 (CD47 Knockout) had significantly less brain neutrophil infiltration at 24h, upregulated VEGF expression in peri-lesion cortex at 7 and 14days, and increased blood vessel density at 21days after TBI, compared to wild type (WT) mice. CD47 knockout also significantly decreased sensorimotor function deficits and reduced brain lesion volume at 21days after TBI. We conclude that CD47 may play pathological roles in brain neutrophil infiltration, progression of brain tissue damage, impairment of cerebrovascular remodeling and functional recovery after TBI.
authors.affiliation: Departments of Orthopedic and Neurosurgery, The First Bethune Hospital of Jilin University, Changchun, Jilin, China; Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: 33528276@qq.com.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: Yu.Zhanyang@mgh.harvard.edu.
authors.forename: Zhanyang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA; Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: liuyuly1982@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Departments of Orthopedic and Neurosurgery, The First Bethune Hospital of Jilin University, Changchun, Jilin, China. Electronic address: 1295915645@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: yjiang6@mgh.harvard.edu.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: kvanleyen@mgh.harvard.edu.
authors.forename: Klaus
authors.initials: K
authors.lastname: van Leyen
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. Electronic address: yy2324@columbia.edu.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA; Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: JLOK1@mgh.harvard.edu.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Lok
authors.affiliation: Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: mwhalen@mgh.harvard.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Whalen
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: lo@helix.mgh.harvard.edu.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2401, Charlestown, MA 02129, USA. Electronic address: wangxi@helix.mgh.harvard.edu.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051928:CD47 Antigen / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse
keywords: Angiopoietin 1 (Ang-1); CD47; Controlled cortical impact (CCI); Neurological severity score (NSS); Neutrophil infiltration; Traumatic brain injury (TBI); Vascular endothelial growth factor (VEGF); Vessel density