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.
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 strokepatients may be useful.
Authors: Jialiang Hu; Philippe E Van den Steen; Qing-Xiang A Sang; Ghislain Opdenakker Journal: Nat Rev Drug Discov Date: 2007-06 Impact factor: 84.694
Authors: G Opdenakker; P E Van den Steen; B Dubois; I Nelissen; E Van Coillie; S Masure; P Proost; J Van Damme Journal: J Leukoc Biol Date: 2001-06 Impact factor: 4.962
Authors: J Montaner; J Alvarez-Sabín; C Molina; A Anglés; S Abilleira; J Arenillas; M A González; J Monasterio Journal: Stroke Date: 2001-08 Impact factor: 7.914
Authors: Anna Rosell; Eloy Cuadrado; Arantxa Ortega-Aznar; Mar Hernández-Guillamon; Eng H Lo; Joan Montaner Journal: Stroke Date: 2008-03-06 Impact factor: 7.914