Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

Arumugam, T V, Woodruff, T M, Lathia, J D, Selvaraj, P K, Mattson, M P and Taylor, S M (2009) Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience, 158 3: 1074-1089. doi:10.1016/j.neuroscience.2008.07.015


Author Arumugam, T V
Woodruff, T M
Lathia, J D
Selvaraj, P K
Mattson, M P
Taylor, S M
Title Neuroprotection in stroke by complement inhibition and immunoglobulin therapy
Journal name Neuroscience   Check publisher's open access policy
ISSN 0306-4522
Publication date 2009-02-06
Year available 2008
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.neuroscience.2008.07.015
Volume 158
Issue 3
Start page 1074
End page 1089
Total pages 16
Place of publication Oxford, U.K.
Publisher Pergamon
Language eng
Subject C1
060804 Animal Immunology
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
1109 Neurosciences
Formatted abstract
Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.
Copyright © 2009 IBRO Published by Elsevier Ltd.

Keyword Ischemic Stroke
Complement
IVIG
Neuron
Apoptosis
Brain injury
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Available online 12 July 2008

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Fri, 10 Apr 2009, 01:08:02 EST by Shirley Rey on behalf of Faculty of Science