title: DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury.
abstract: Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke. The aim of the current study was to determine if DRα1-MOG-35-55 treatment of a fluid percussion injury (FPI) mouse model of TBI could reduce the lesion size and improve disease outcome measures. Neurodeficits, lesion size, and immune responses were determined to evaluate the therapeutic potential and mechanisms of neuroprotection induced by DRα1-MOG-35-55 treatment. The results demonstrated that daily injections of DRα1-MOG-35-55 given after FPI significantly reduced numbers of infiltrating CD74+and CD86+macrophages and increased numbers of CD206+microglia in the brain concomitant with smaller lesion sizes and improvement in neurodeficits. Conversely, DRα1-MOG-35-55 treatment of TBI increased numbers of circulating CD11b+monocytes and their expression of CD74 but had no detectable effect on cell numbers or marker expression in the spleen. These results demonstrate that DRα1-MOG-35-55 therapy can reduce CNS inflammation and significantly improve histological and clinical outcomes after TBI. Future studies will further examine the potential of DRα1-MOG-35-55 for treatment of TBI.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Siman
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: "2011"Collaborative Innovation Center/Neurobiology Research Center, Shanxi University of Traditional Chinese Medicine, Taiyuan, Shanxi, 030619, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chai
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Meza-Romero
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Benedek
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA.|Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.|Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. offnerva@ohsu.edu.|Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.|Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. offnerva@ohsu.edu.|Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. minshuli2012@163.com.|St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA. minshuli2012@163.com.
authors.forename: Minshu
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001921:Brain / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003001:Cloning, Molecular; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007958:Leukocyte Count; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D039481:CD11b Antigen; C000627789:DRalpha1-MOG-35-55; D000949:Histocompatibility Antigens Class II; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C045084:invariant chain
keywords: CD74; DRα1-MOG-35-55 therapy; Infiltrating macrophages/microglia; Neurological deficits; Traumatic brain injury