Our study suggested that: (1) EC necroptosis was activated in ischemic penumbra after I/R injury; (2) EC necroptosis increased BBB permeability and ischemic brain injury; (3) M1-like microglial-derived TNF-α induced EC necroptosis; (4) NF-κB nuclear translocation increased the expression of TNF-α in M1-like microglia after I/R injury, and (5) Infliximab, a potent clinical drug blocks TNF-α, could ameliorate BBB disruption and stroke damage. The gene discussed is TNF; the disease is stroke disorder.