Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury.

ABSTRACT: The mechanism and long-term consequences of early blood-brain barrier (BBB) disruption after cerebral ischaemic/reperfusion (I/R) injury are poorly understood. Here we discover that I/R induces subtle BBB leakage within 30-60 min, likely independent of gelatinase B/MMP-9 activities. The early BBB disruption is caused by the activation of ROCK/MLC signalling, persistent actin polymerization and the disassembly of junctional proteins within microvascular endothelial cells (ECs). Furthermore, the EC alterations facilitate subsequent infiltration of peripheral immune cells, including MMP-9-producing neutrophils/macrophages, resulting in late-onset, irreversible BBB damage. Inactivation of actin depolymerizing factor (ADF) causes sustained actin polymerization in ECs, whereas EC-targeted overex

SUBMITTER: Shi Y 

PROVIDER: S-EPMC4737895 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature