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Title: Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats
Authors: Park, Kyung-Pil ×
Rosell, Anna
Foerch, Christian
Xing, Changhong
Kim, Woo Jean
Lee, Seoul
Opdenakker, Ghislain
Furie, Karen L
Lo, Eng H #
Issue Date: Aug-2009
Publisher: Lippincott Williams & Wilkins
Series Title: Stroke vol:40 issue:8 pages:2836-2842
Abstract: BACKGROUND AND PURPOSE: Plasma levels of matrix metalloproteinase-9 (MMP-9) have been proposed to be a useful biomarker for assessing pathological events in brain. Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia. METHODS: Plasma and brain levels of MMP-2 and MMP-9 were quantified at 3, 6, 12, and 24 hours after permanent middle cerebral artery occlusion in male Sprague-Dawley rats. Infarct volumes at 24 hours were confirmed with 2,3,5-triphenyl-tetrazolium-chloride staining. RESULTS: In plasma, zymographic bands were detected between 70 and 95 kDa corresponding to pro-MMP-2, pro-MMP-9, and activated MMP-9. A higher 135-kDa band was also seen that is likely to be NGAL-conjugated MMP-9. After ischemia, there were no significant changes in pro-MMP-2, but plasma levels of pro-MMP-9 steadily increased over the course of 24 hours. Activated MMP-9 levels in plasma were significantly elevated only at 24 hours. Plasma NGAL-MMP-9 complexes showed a transient elevation between 3 to 6 hours, after which levels decreased back down to pre-ischemic baselines. In brain homogenates, pro-MMP-2, pro-MMP-9, and activated MMP-9 were seen but no NGAL-MMP-9 bands were detected. Compared to the contralateral hemisphere, MMP-2 and MMP-9 levels in ischemic brain progressively increased over the course of 24 hours. Overall levels of MMP-9 in plasma and brain were significantly correlated, especially at 24 hours. Plasma levels of pro-MMP-9 at 24 hours were correlated with final infarct volumes. CONCLUSIONS: Elevated plasma levels of MMP-9 appear to be correlated with brain levels within 24 hours of acute cerebral ischemia in rats. Further investigation into clinical profiles of MMP-9 in acute stroke patients may be useful.
URI: 
ISSN: 0039-2499
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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