Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats.
OBJECTIVE
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.
Park
Kyung-Pil
KP
Neuroprotection Research Laboratory, MGH East 149-2401 Charlestown, MA 02129, USA.
Rosell
Anna
A
Foerch
Christian
C
Xing
Changhong
C
Kim
Woo Jean
WJ
Lee
Seoul
S
Opdenakker
Ghislain
G
Furie
Karen L
KL
Lo
Eng H
EH
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood* / Q000201:enzymology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9