We also show that injection of HMGB1 into normal rat cortex results in the expression of TLR4, and downstream signaling elements, in perilesional (HMGB1 injection site) astrocytes, compared to injection of vehicle, thereby suggesting that HMGB1 contributes to TLR4 signaling in vivo during focal cerebral ischemia. This evidence concerns the gene HMGB1 and brain ischemia.