title: 2-BFI ameliorates EAE-induced mouse spinal cord damage: effective therapeutic time window and possible mechanisms.
abstract: Our previous studies showed that ligands to type 2 imidazoline receptors (I₂R), including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective in reducing spinal cord inflammation caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we determined the effective therapeutic time window of 2-BFI and found that administration of 2-BFI in mice before the appearance of ascending flaccid paralysis (1-10 days post immunization), but not during the period when neurological deficits occurred (11-20 days post immunization), significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord, and reduced the level of demyelination. More interestingly, giving 2-BFI during 1-10 days post immunization selectively suppressed IL-17 levels in the peripheral blood, which strongly suggests that IL-17 may be a good early marker to indicate EAE progression and that 2-BFI may target CD4⁺ T lymphocytes, especially Th17 cells to reduce IL-17 expression. Collectively, these studies led us to envisage that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in combination with an early indicator of MS progression, such as IL-17.
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, No. 2 Fuxue Lane, Wenzhou City, Zhejiang Province 325000, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Zheng-Xue
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Yin-Feng
authors.initials: YF
authors.lastname: Liu
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Xu
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Hou
authors.forename: Rong-Yuan
authors.initials: RY
authors.lastname: Zheng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000633:toxicity; D007093:Imidazoles / Q000627:therapeutic use*; D007211:Indoles; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D010446:Peptide Fragments / Q000633:toxicity; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D001572:Benzofurans; D002135:Calcium-Binding Proteins; D016207:Cytokines; D007093:Imidazoles; D007211:Indoles; D008840:Microfilament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C018588:Luxol Fast Blue MBS; C103723:2-(2-benzofuranyl)-2-imidazoline; D005620:Freund's Adjuvant