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(Stroke. 2009;40:2836.)
© 2009 American Heart Association, Inc.

Original Contributions

Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in Rats

Kyung-Pil Park, MD; Anna Rosell, PhD; Christian Foerch, MD; Changhong Xing, PhD; Woo Jean Kim, PhD; Seoul Lee, PhD; Ghislain Opdenakker, MD, PhD; Karen L. Furie, MD Eng H. Lo, PhD

From the Departments of Neurology and Radiology (K.P., A.R., C.F., C.X., W.J.K., S.L., K.L.F., E.H.L.), Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; Department of Neurology (K.P.), Pusan National University Yangsan Hospital, Medical Research Institute, Pusan National University, Busan, Korea; Rega Institute for Medical Research (G.O.), Catholic University of Leuven, Leuven, Belgium.

Correspondence to Eng H. Lo, PhD, Neuroprotection Research Laboratory, MGH East 149-2401 Charlestown, MA 02129. E-mail Lo{at}helix.mgh.harvard.edu; or Kyung-Pil Park, MD, Department of Neurology, Pusan National University Yangsan Hospital, Busan, Korea. E-mail kppark@pusan.ac.kr

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.

Key Words: cerebral ischemia • matrix metalloproteinase • stroke