https://scholars.lib.ntu.edu.tw/handle/123456789/519419
標題: | Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death | 作者: | Arumugam T.V. SUNG-CHUN TANG Lathia J.D. Cheng A. Mughal M.R. Chigurupati S. Magnus T. Chan S.L. Jo D.-G. Ouyang X. Fairlie D.P. Granger D.N. Vortmeyer A. Basta M. Mattson M.P. |
公開日期: | 2007 | 卷: | 104 | 期: | 35 | 起(迄)頁: | 14104-14109 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | Stroke is among the three leading causes of death worldwide and the most frequent cause of permanent disability. Brain ischemia induces an inflammatory response involving activated complement fragments. Here we show that i.v. Ig (IVIG) treatment, which scavenges complement fragments, protects brain cells against the deleterious effects of experimental ischemia and reperfusion (I/R) and prevents I/R-induced mortality in mice. Animals administered IVIG either 30 min before ischemia or after 3 h of reperfusion exhibited a 50-60% reduction of brain infarct size and a 2- to 3-fold improvement of the functional outcome. Even a single low dose of IVIG given after stroke was effective. IVIG was protective in the nonreperfusion model of murine stroke as well and did not exert any peripheral effects. Human IgG as well as intrinsic murine C3 levels were significantly higher in the infarcted brain region compared with the noninjured side, and their physical association was demonstrated by immuno-coprecipitation. C5-deficient mice were significantly protected from I/R injury compared with their wild-type littermates. Exposure of cultured neurons to oxygen/glucose deprivation resulted in increased levels of C3 associated with activation of caspase 3, a marker of apoptosis; both signals were attenuated with IVIG treatment. Our data suggest a major role for complement-mediated cell death in ischemic brain injury and the prospect of using IVIG in relatively low doses as an interventional therapy for stroke. ? 2007 by The National Academy of Sciences of the USA. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-35348848463&doi=10.1073%2fpnas.0700506104&partnerID=40&md5=1e95d1a8973f12b9d0a3833d09fea057 https://scholars.lib.ntu.edu.tw/handle/123456789/519419 |
ISSN: | 0027-8424 | DOI: | 10.1073/pnas.0700506104 | SDG/關鍵字: | caspase 3; complement; complement component C3; complement component C5; immunoglobulin; immunoglobulin G; complement component C5; immunoglobulin; immunologic factor; animal experiment; animal model; animal tissue; article; brain infarction size; brain protection; cerebrovascular accident; complement blood level; controlled study; enzyme activation; immunoglobulin blood level; lymphocyte; male; microglia; mouse; nerve cell necrosis; nonhuman; priority journal; animal; brain; brain cortex; brain infarction; cell death; disease model; drug administration; drug effect; immunology; mouse mutant; nerve cell; pathology; Animalia; Murinae; Mus; Animals; Brain; Cell Death; Cerebral Cortex; Cerebral Infarction; Complement C5; Disease Models, Animal; Drug Administration Schedule; Immunoglobulins, Intravenous; Immunologic Factors; Mice; Mice, Knockout; Neurons |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。