title: Role of C16, angiopoietin-1 and regeneration gene protein 2 in attenuating inflammation in an experimental rat model of autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits. Our results demonstrated that triple combination therapy was more efficient than the monotherapy in EAE treatment. The triple therapy significantly delayed the onset of motor symptoms, reduced disease severity, attenuated inflammatory cell infiltration and suppressed the secretion of proinflammatory cytokines. Additionally, treatment increased anti-inflammatory cytokines expression, inhibited reactive astrocytes proliferation, reduced demyelination and axonal loss, and finally reduced the neural death. Specifically, Reg-2 administration rescued oligodendrocytes and neuronal axons mainly by direct neurotrophic effects, while C16+Ang-1 (C+A) mainly improved the inflammatory milieu. In conclusion, our study suggests a possible synergistic effect through targeting a variety of pathways in relieving the clinical symptoms of inflammation in acute EAE model. Therefore, using molecules that target different molecular pathways can be beneficial for exploring novel therapeutic approaches for MS treatment.
authors.affiliation: Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Tian
authors.affiliation: Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Electrophysiology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Core Facilities, Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Han
mesh_terms: D042683:Angiopoietin-1 / Q000008:administration & dosage*; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D037181:Lectins, C-Type / Q000008:administration & dosage*; D008297:Male; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D042683:Angiopoietin-1; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments; C000612142:Reg2 protein, rat
keywords: C16; angiopoietin-1; complementary effects; encephalomyelitis; regeneration gene protein 2