Peroxiredoxin triggers cerebral post-ischemic inflammation

Post-ischemic inflammation is an essential step in the progression of ischemic stroke. However, it has not been sufficiently clarified how post-ischemic inflammation begins. Brain is a sterile organ, but Toll-like receptor (TLR) 2 and TLR4 have a pivotal role in the initiation of inflammation. Some endogenous danger associated molecular patterns (DAMPs) are released from injured brain cells. Among them, high mobility group box 1 (HMGB1) and peroxiredoxin (Prx) family proteins are key initiators of post-ischemic inflammation. HMGB1 induces blood brain barrier breakdown at the hyperacute phase; on the other hand, Prxs directly activate infiltrating macrophage through TLR2/4 and induce inflammatory cytokines production at the acute phase. Thus, there is a time lag as well as functional differences between HMGB1 and Prxs. Novel neuroprotective treatment could be developed through more detailed elucidation of the regulation of post-ischemic inflammation.