PMID- 17715065
OWN - NLM
STAT- MEDLINE
DCOM- 20071017
LR  - 20240322
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 35
DP  - 2007 Aug 28
TI  - Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke 
      by preventing complement-mediated neuronal cell death.
PG  - 14104-9
AB  - 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.
FAU - Arumugam, Thiruma V
AU  - Arumugam TV
AD  - Laboratory of Neurosciences, National Institute on Aging Intramural Research 
      Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
FAU - Tang, Sung-Chun
AU  - Tang SC
FAU - Lathia, Justin D
AU  - Lathia JD
FAU - Cheng, Aiwu
AU  - Cheng A
FAU - Mughal, Mohamed R
AU  - Mughal MR
FAU - Chigurupati, Srinivasulu
AU  - Chigurupati S
FAU - Magnus, Tim
AU  - Magnus T
FAU - Chan, Sic L
AU  - Chan SL
FAU - Jo, Dong-Gyu
AU  - Jo DG
FAU - Ouyang, Xin
AU  - Ouyang X
FAU - Fairlie, David P
AU  - Fairlie DP
FAU - Granger, Daniel N
AU  - Granger DN
FAU - Vortmeyer, Alexander
AU  - Vortmeyer A
FAU - Basta, Milan
AU  - Basta M
FAU - Mattson, Mark P
AU  - Mattson MP
LA  - eng
GR  - R01 HL026441/HL/NHLBI NIH HHS/United States
GR  - HL26441/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070821
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Complement C5)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Immunologic Factors)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/immunology/pathology
MH  - Cell Death/*drug effects
MH  - Cerebral Cortex/drug effects/immunology/pathology
MH  - Cerebral Infarction/immunology/*prevention & control
MH  - Complement C5/deficiency
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Immunoglobulins, Intravenous/*therapeutic use
MH  - Immunologic Factors/therapeutic use
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/drug effects/*pathology
PMC - PMC1955802
COIS- The authors declare no conflict of interest.
EDAT- 2007/08/24 09:00
MHDA- 2007/10/18 09:00
PMCR- 2008/02/28
CRDT- 2007/08/24 09:00
PHST- 2007/08/24 09:00 [pubmed]
PHST- 2007/10/18 09:00 [medline]
PHST- 2007/08/24 09:00 [entrez]
PHST- 2008/02/28 00:00 [pmc-release]
AID - 0700506104 [pii]
AID - 7491 [pii]
AID - 10.1073/pnas.0700506104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14104-9. doi: 
      10.1073/pnas.0700506104. Epub 2007 Aug 21.