Stroke therapy targeting innate immunity

Abstract

Post-ischemic inflammation is re-appraised as an important player in the progression of ischemic stroke. Activation of inflammatory cells via Toll-like receptor (TLR) is caused by several damage-associated molecular patterns (DAMPs), including high mobility group box-1 and nucleotides. We have recently found that peroxiredoxin (Prx) is one of the strong DAMPs and activates infiltrating macrophages via TLR2 and TLR4 in brain ischemia. We have also found that interleukin-23 (IL-23) from the activated macrophages stimulates γδT cells which release IL-17, thereby causing the delayed expansion of infarct lesions. Further investigation of the innate immune response would lead to development of novel stroke treatment with a broad therapeutic time window.