There is growing evidence from preclinical rodent studies that extracellular HMGB1 drives maladaptive pro-inflammatory processes during the acute phase of ischemia through receptors like RAGE, TLR2, and TLR4 which lead to expansion of infarct size and worsened functional outcomes (Muhammad et al., 2008; Hayakawa, Qiu & Lo, 2010). This evidence concerns the gene HMGB1 and ischemia.