PMID- 28303450 OWN - NLM STAT- MEDLINE DCOM- 20180723 LR - 20230808 IS - 1573-7365 (Electronic) IS - 0885-7490 (Print) IS - 0885-7490 (Linking) VI - 32 IP - 5 DP - 2017 Oct TI - DRalpha1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury. PG - 1395-1402 LID - 10.1007/s11011-017-9991-6 [doi] AB - 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)-DRalpha1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRalpha1-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 DRalpha1-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 DRalpha1-MOG-35-55 treatment. The results demonstrated that daily injections of DRalpha1-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, DRalpha1-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 DRalpha1-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 DRalpha1-MOG-35-55 for treatment of TBI. FAU - Yang, Liu AU - Yang L AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. AD - St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA. FAU - Liu, Zhijia AU - Liu Z AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. FAU - Ren, Honglei AU - Ren H AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. FAU - Zhang, Lei AU - Zhang L AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. FAU - Gao, Siman AU - Gao S AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. FAU - Ren, Li AU - Ren L AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. FAU - Chai, Zhi AU - Chai Z AD - "2011"Collaborative Innovation Center/Neurobiology Research Center, Shanxi University of Traditional Chinese Medicine, Taiyuan, Shanxi, 030619, China. FAU - Meza-Romero, Roberto AU - Meza-Romero R AD - Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. AD - Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA. FAU - Benedek, Gil AU - Benedek G AD - Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. AD - Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA. AD - Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. FAU - Vandenbark, Arthur A AU - Vandenbark AA AD - Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. AD - Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA. AD - Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. AD - Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA. FAU - Offner, Halina AU - Offner H AD - Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA. offnerva@ohsu.edu. AD - Tykeson MS Research Laboratory, Department of Neurology UHS-46, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu. AD - Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. offnerva@ohsu.edu. AD - Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu. FAU - Li, Minshu AU - Li M AD - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. minshuli2012@163.com. AD - St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA. minshuli2012@163.com. LA - eng GR - R01 NS076013/NS/NINDS NIH HHS/United States GR - R01 NS075887/NS/NINDS NIH HHS/United States GR - R42 AI122574/AI/NIAID NIH HHS/United States GR - R44 AI122574/AI/NIAID NIH HHS/United States GR - R01 NS092713/NS/NINDS NIH HHS/United States GR - I01 BX000226/BX/BLRD VA/United States GR - R41 AI122574/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170316 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (CD11b Antigen) RN - 0 (DRalpha1-MOG-35-55) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (invariant chain) SB - IM MH - Animals MH - Antigens, Differentiation, B-Lymphocyte/metabolism MH - Brain/pathology MH - Brain Injuries, Traumatic/complications/*drug therapy/pathology MH - CD11b Antigen/metabolism MH - Cloning, Molecular MH - Histocompatibility Antigens Class II/metabolism MH - Leukocyte Count MH - Macrophages/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/drug effects MH - Nervous System Diseases/*drug therapy/etiology MH - Neuroprotective Agents/chemical synthesis/*therapeutic use MH - Recombinant Fusion Proteins/chemical synthesis/*therapeutic use MH - Treatment Outcome PMC - PMC5600636 MID - NIHMS860880 OTO - NOTNLM OT - CD74 OT - DRalpha1-MOG-35-55 therapy OT - Infiltrating macrophages/microglia OT - Neurological deficits OT - Traumatic brain injury COIS- Conflict of Interest: Drs. Vandenbark, Offner, Benedek, Meza-Romero and OHSU have a significant financial interest in Artielle ImmunoTherapeutics, Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU and VA Portland Health Care System Conflict of Interest in Research Committees. The other authors (Liu Yang, Zhijia Liu, Honglei Ren, Lei Zhang, Siman Gao, Li Ren, Zhi Chai, and Minshu Li) declare no conflicts of interest. EDAT- 2017/03/18 06:00 MHDA- 2018/07/24 06:00 PMCR- 2018/10/01 CRDT- 2017/03/18 06:00 PHST- 2017/01/31 00:00 [received] PHST- 2017/03/08 00:00 [accepted] PHST- 2017/03/18 06:00 [pubmed] PHST- 2018/07/24 06:00 [medline] PHST- 2017/03/18 06:00 [entrez] PHST- 2018/10/01 00:00 [pmc-release] AID - 10.1007/s11011-017-9991-6 [pii] AID - 10.1007/s11011-017-9991-6 [doi] PST - ppublish SO - Metab Brain Dis. 2017 Oct;32(5):1395-1402. doi: 10.1007/s11011-017-9991-6. Epub 2017 Mar 16.