期刊
JOURNAL OF NEUROCHEMISTRY
卷 129, 期 1, 页码 130-142出版社
WILEY-BLACKWELL
DOI: 10.1111/jnc.12607
关键词
blood-brain barrier; hemorrhagic transformation; matrix metalloproteinases; neuroinflammation; neutrophil recruitment; vasogenic edema
资金
- NIH (NINDS) [NS065849]
- Brain and Spinal Cord Injury Research Trust Fund, McKnight Brain Institute, University of Florida
Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A(4) (LXA(4)) is an anti-inflammatory, pro-resolution lipid mediator with high affinity binding to ALX, the lipoxin A(4) receptor. Since LXA(4) is rapidly inactivated, potent analogs have been created, including the ALX agonist BML-111. We hypothesized that post-ischemic intravenous administration of BML-111 would provide protection to the neurovascular unit and reduce neuroinflammation in a rat stroke model. Animals were subjected to 90 min of middle cerebral artery occlusion (MCAO) and BML-111 was injected 100 min and 24 h after stroke onset and animals euthanized at 48 h. Post-ischemic treatment with BML-111 significantly reduced infarct size, decreased vasogenic edema, protected against blood-brain barrier disruption, and reduced hemorrhagic transformation. Matrix metalloproteinase-9 and matrix metalloproteinase-3 were significantly reduced following BML-111 treatment. Administration of BML-111 dramatically decreased microglial activation, as seen with CD68, and neutrophil infiltration and recruitment, as assessed by levels of myeloperoxidase and intracellular adhesion molecule-1. The tight junction protein zona occludens-1 was protected from degradation following treatment with BML-111. These results indicate that post-ischemic activation of ALX has pro-resolution effects that limit the inflammatory damage in the cerebral cortex and helps maintain blood-brain barrier integrity after ischemic stroke.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据