Angiopoietin-1 ameliorates inflammation-induced vascular leakage and improves functional impairment in a rat model of acute experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) is characterized by perivascular inflammatory infiltration, secondary demyelination, and axonal loss in the central nervous system. Angiopoietin-1 (Ang-1) constitutes a family of endothelial growth factors that can inhibit MS-associated, inflammation-induced blood vascular leakage and lessen increased blood vessel permeability. This study was designed to investigate the effects of Ang-1 on a model of acute experimental autoimmune encephalomyelitis (EAE). Evans blue and the luciferase assay were employed to test blood vessel permeability, while immunohistochemistry, ELISA, and Western blotting were used to assess the degree of inflammation. Electron microscopy and cortical somatosensory evoked potentials were also used to observe axonal loss, white matter demyelination, and functional impairment in EAE groups. Our results showed that Ang-1 treatment could ameliorate inflammation-induced leakage, inhibit inflammatory cell infiltration into the brain and spinal cord, and improve functional impairment associated with EAE in a dose-dependent manner.
Department of Neuroelectrophysiology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, China. Electronic address: lzf118@163.com.
Hong
H
Jiang
Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China. Electronic address: 478207793@qq.com.
Fan
F
Zhang
Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China. Electronic address: yangjing_422@126.com.
Jing
J
Yang
Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China. Electronic address: han00shu@zju.edu.cn.
Shu
S
Han
D042683:Angiopoietin-1 / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000276:immunology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000187:drug effects; D016622:Silver Staining
D042683:Angiopoietin-1; D016207:Cytokines; D016228:Endothelial Growth Factors
Angiopoietin-1; Experimental autoimmune encephalomyelitis; Inflammation-induced blood vessel leakage; Microenvironment; Multiple sclerosis