Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death

Arumugam, T. V, Tang, S. C, 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 and Mattson, M. P (2007) Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proceedings of The National Academy of Sciences of The United States of America, 104 35: 14104-14109. doi:10.1073/pnas.0700506104


Author Arumugam, T. V
Tang, S. C
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
Title Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death
Journal name Proceedings of The National Academy of Sciences of The United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2007
Sub-type Article (original research)
DOI 10.1073/pnas.0700506104
Open Access Status Not Open Access
Volume 104
Issue 35
Start page 14104
End page 14109
Total pages 6
Place of publication Washington
Publisher National Academy of Sciences
Collection year 2008
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
670403 Treatments (e.g. chemicals, antibiotics)
Abstract 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.
Keyword Multidisciplinary Sciences
C5a
cerebral cortex apoptosis
ischemic stroke
lymphocyte
microglia
Focal Cerebral-ischemia
Tissue-plasminogen-activator
Human Albumin
Therapy
C5a
Neuroprotection
Perfusion
Adhesion
Receptor
System
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 18 Feb 2008, 14:56:16 EST