Journal
STROKE
Volume 40, Issue 12, Pages 3872-3875Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.109.566109
Keywords
apoptosis; caspase-1 inhibitor; pulmonary edema; subarachnoid hemorrhage
Categories
Funding
- National Institutes of Health [NS053407]
Ask authors/readers for more resources
Background and Purpose-We examined the effects of a caspase-1 inhibitor, N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK), on neurogenic pulmonary edema in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice. Methods-Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10 mg/kg), and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6 mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1 beta, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens-1, MMP zymography, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, and immunostaining were performed on the lung at 24 hours post-SAH. Results-Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1 beta and caspase-3 and the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive pulmonary endothelial cells, preventing neurogenic pulmonary edema. Another antiapoptotic drug, Z-VAD-FMK, also reduced neurogenic pulmonary edema. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, zona occludens-1 levels, or MMP activity. Conclusions-We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and neurogenic pulmonary edema after SAH in mice. (Stroke. 2009;40:3872-3875.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available