Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke

Post‐ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll‐like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post‐ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and 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 γδT cells function as neurotoxic (IL‐23/IL‐17, IFN‐γ) or neuroprotective (IL‐10, IL‐4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post‐ischemic inflammation.

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