Inflammatory Changes in Cerebral Ischemic Injury: Cellular and Molecular Involvement
Post-ischemic inflammation is an essential step in the progression of ischemic stroke. Recently, important roles of infiltrating immune cells, macrophages, and T cells in ischemic brain injury have been clarified. The activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post-ischemic inflammation. Several damage-associated molecular patterns (DAMPs)—endogenous TLR ligands—are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and these activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate post-ischemic inflammation in the delayed phase. Various cytokines from helper T cells and γδ T cells function as neurotoxic or neuroprotective mediators. Resolution of inflammation is another important step in ischemic injury, and infiltrating macrophages in the late stage work to clear DAMPs. Novel neuroprotective strategies could be developed through further understanding of this process and the regulation of post-ischemic inflammation.