PMID- 18691639
OWN - NLM
STAT- MEDLINE
DCOM- 20090508
LR  - 20231105
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 158
IP  - 3
DP  - 2009 Feb 6
TI  - Neuroprotection in stroke by complement inhibition and immunoglobulin therapy.
PG  - 1074-89
LID - 10.1016/j.neuroscience.2008.07.015 [doi]
AB  - 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.
FAU - Arumugam, T V
AU  - Arumugam TV
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University 
      Health Sciences Center, 1300 Coulter Drive, Amarillo, TX 79106, USA. 
      thiruma.arumugam@ttuhsc.edu
FAU - Woodruff, T M
AU  - Woodruff TM
FAU - Lathia, J D
AU  - Lathia JD
FAU - Selvaraj, P K
AU  - Selvaraj PK
FAU - Mattson, M P
AU  - Mattson MP
FAU - Taylor, S M
AU  - Taylor SM
LA  - eng
GR  - Z01 AG000314-07/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20080712
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Anaphylatoxins)
RN  - 0 (Complement Inactivating Agents)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Anaphylatoxins/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Brain Infarction/*drug therapy/*immunology/physiopathology
MH  - Chemotaxis, Leukocyte/drug effects/immunology
MH  - Complement Inactivating Agents/*therapeutic use
MH  - Complement System Proteins/drug effects/metabolism
MH  - Cytoprotection/drug effects/*immunology
MH  - Encephalitis/drug therapy/immunology/physiopathology
MH  - Humans
MH  - Immunoglobulins, Intravenous/pharmacology/*therapeutic use
MH  - Microglia/drug effects/immunology
MH  - Stroke/*drug therapy/*immunology/physiopathology
PMC - PMC2639633
MID - NIHMS68910
EDAT- 2008/08/12 09:00
MHDA- 2009/05/09 09:00
PMCR- 2009/08/06
CRDT- 2008/08/12 09:00
PHST- 2008/05/13 00:00 [received]
PHST- 2008/07/08 00:00 [revised]
PHST- 2008/07/08 00:00 [accepted]
PHST- 2008/08/12 09:00 [pubmed]
PHST- 2009/05/09 09:00 [medline]
PHST- 2008/08/12 09:00 [entrez]
PHST- 2009/08/06 00:00 [pmc-release]
AID - S0306-4522(08)01039-7 [pii]
AID - 10.1016/j.neuroscience.2008.07.015 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Feb 6;158(3):1074-89. doi: 10.1016/j.neuroscience.2008.07.015. 
      Epub 2008 Jul 12.