The enhanced vascular permeability is a major early
brain injury following
subarachnoid hemorrhage (SAH). However, its mechanism is not clear yet. In this work, we explored its potential mechanism and investigated the roles of
thrombomodulin (TM) in maintaining microvascular integrity after SAH. SAH models were established in adult male ICR mice (28-32 g) by endovascular perforation. TM was immediately administered by femoral vein injection following SAH. The brain water content,
Evans Blue content and neurological functions were evaluated.
Brain edema was also detected by magnetic resonance imaging (MRI) (T2 map). The
siRNA technique,
enzyme-linked
immunosorbent assay (ELISA), immunofluorescence staining and western blotting were performed to explore the potential mechanism of TM treatment. The number of microthrombi in the hippocampus microvessels was also recorded. TM significantly decreased brain water content and
Evans Blue content, alleviated
brain edema and neurological deficits after SAH. The plasma concentration of activated
protein C was increased after TM treatment. In addition, the levels of phospho-p38MAPK, phospho-p53, cleaved
caspase-3, phospho-NF-κB (p65) were markedly decreased. Additionally, the loss of
VE-cadherin and
Occludin (markers of vascular integrity) and the number of microthrombi in the hippocampus were also reduced. Our results indicated that TM has protective effects on preserving microvascular integrity following SAH partly through preserving endothelial junction
proteins and quenching apoptosis/
inflammation in endothelial cells via blocking p38MAPK-p53/NF-κB (p65) pathway.