Inflammation and the emerging role of the toll-like receptor system in acute brain ischemia.
OBJECTIVE
Systemic administration of cytosine-guanine (CpG) oligodeoxynucleotides provides neuroprotection against subsequent cerebral ischemic injury. We examined the genomic response of leukocytes and brain cells after ischemia in the context of CpG preconditioning.


METHODS
RNA was isolated from circulating leukocytes and ischemic cortex 3 and 24 hours after middle cerebral artery occlusion after CpG or saline pretreatment and subjected to microarray analysis. Genes uniquely upregulated in CpG-pretreated mice were examined for overrepresented transcriptional regulatory elements.


RESULTS
CpG preconditioning induced a novel response to middle cerebral artery occlusion within circulating leukocytes that was dominated by natural killer cell-associated genes and the GATA-3 transcriptional regulatory element. Preconditioning also caused a novel brain response to stroke that was dominated by Type I interferon, interferon-associated genes, and transcriptional regulatory elements.


CONCLUSIONS
CpG preconditioning invokes novel leukocyte and brain responses to stroke. In this, CpG may be a unique preconditioning agent, coordinating peripheral and brain responses to protect against ischemic injury.
Marsh
Brenda J
BJ
Department of Molecular Microbiology and Immunology, L220, Oregon Health & Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
Stevens
Susan L
SL
Hunter
Brian
B
Stenzel-Poore
Mary P
MP
D000208:Acute Disease; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D019194:Ischemic Preconditioning; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D051193:Toll-Like Receptors / Q000502:physiology*
D015226:Dinucleoside Phosphates; D050990:GATA3 Transcription Factor; D007370:Interferon Type I; D051193:Toll-Like Receptors; C015772:CpG dinucleotide