HMGB1 is a potent inducer of post‐ischaemic inflammation,23 whose levels correlate with the severity and outcome of ischaemic stroke.24 The primary receptors of HMGB1 implicated in brain injury are advanced glycation end products (RAGE), TLR2 and TLR4.23, 25, 26, 27 Both TLRs and RAGE are important for mediating astrocytic activation, blockage of TLRs or RAGE signal would suppress activated astrocytes and be beneficial for brain ischaemic injury.28, 29, 30 Our further study found that SsnB, the blocker of TLR2/TLR4, could abolish protection of pFTY720. The gene discussed is TLR4; the disease is ischemic stroke.