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.

Keyword

Aging/*genetics

Animals

Cell Adhesion/genetics

Chemokines/genetics

*Gene Expression Profiling

Gene Expression Regulation

Histocompatibility Antigens Class I/genetics

Histocompatibility Antigens Class II/genetics

Hypoxia-Ischemia

Brain/*genetics/*pathology

Immunohistochemistry

Inflammation/*genetics

Interferons/genetics

Leukocytes/metabolism

Macrophages/metabolism

Mice

Publication and Content Type

ref (subject category)

art (subject category)