Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia.
Brain ischemia triggers an inflammatory reaction that progresses for days to weeks and seems to have a role in secondary progression of injury. Inflammation induces a complex pattern of signaling molecules with partly contradictory actions, and the responses may be different in the immature and adult brain. The authors characterized the global inflammatory gene expression in the developing brain as a first step toward understanding the protective and deleterious effects of inflammation after hypoxia-ischemia. Oligonucleotide arrays were used to investigate inflammatory genes in cortex, hippocampus, thalamus, and striatum at 2, 8, 24, and 72 hours after hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia. After hypoxia-ischemia, 148 inflammatory genes were differentially expressed. More than 97% of the genes were upregulated and 93% had not previously been reported after hypoxia-ischemia in the immature brain. The results indicate that microglia/macrophages, T- and B-cells, NK-cells, mast cells, dendritic cells, and polymorphonuclear leukocytes may participate in the response to hypoxia-ischemia. In addition, novel cytokines/chemokines, complement-related, interferon-regulated, components of the TIR/nuclear factor-kappaB pathway, and a number of immunomodulatory genes were induced. Several of these genes may of pathophysiologic significance after neonatal hypoxia-ischemia.
Hedtjärn
Maj
M
Department of Physiology, Perinatal Center, Göteborg, University, Göteborg, Sweden. maj.hedtjarn@fysiologi.gu.se
Mallard
Carina
C
Hagberg
Henrik
H
D000375:Aging / Q000235:genetics*; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics* / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics*; D007372:Interferons / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice
D018925:Chemokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007372:Interferons