Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke

Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We…

• NR
  National Research Foundation
• NN
  National Natural Science Foundation of China

  Awards: 81400969, 81601027, No. 81571119, No. 81400969, 81671147, 81400970, 2018YFC1312200, 81571119, 81771249
• PF
  Program for New Century Excellent Talents in University

  Awards: NCET-10, NCET-10-0406
• NK
  National Key Research and Development Program of China

  Awards: 2016YFC1300600, 2018YFC1312200