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- W1968071092 abstract "To the Editor:We thank Drs Pfefferkorn and Rosenberg for their enlightening paper1 on matrix metalloproteinases (MMPs) after ischemic stroke.MMPs are attributed an important role in the pathophysiology of cerebral ischemia. The gelatinases MMP-2 and MMP-9 are of particular interest in this respect. In numerous experimental settings, the reduction of gelatinase activity has been demonstrated to be associated with improved outcome. Beside natural MMP inhibitors (tissue inhibitors of MMPs),2 monoclonal antibodies,3 and genetic approaches,4 the broad-spectrum MMP inhibitors BB-94, BB-1101, and KB-R7785 have proven to reduce ischemic damage.1,4–8In addition to their inhibitory effects on MMPs, broad-spectrum inhibitors impede the activity of other metalloendopeptidases such as tumor necrosis factor α (TNF-α) converting enzyme (TACE), which cleaves membrane-bound pro–TNF-α to active soluble TNF-α.9,10 TACE is inhibited by BB-94,11,12,13 BB-1101,14,15 and KB-R7785.16 TNF-α has been proven to display negative effects after cerebral ischemia,17 and its neutralization ameliorates ischemic lesions.17,18,19,20 TNF-α contributes to the opening of the blood–brain barrier (BBB) by a mechanism involving soluble guanylyl cyclase and protein tyrosine kinase.21 Therefore, broad-spectrum MMP inhibitors could have contributed to BBB protection via reducing TNF-α activity and not exclusively via inhibition of MMPs. Unfortunately, the literature on the impact of MMP inhibitors …" @default.
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- W1968071092 date "2004-07-01" @default.
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- W1968071092 title "Cerebral Ischemia, Matrix Metalloproteinases, and TNF-α: MMP Inhibitors May Act Not Exclusively by Reducing MMP Activity" @default.
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- W1968071092 doi "https://doi.org/10.1161/01.str.0000135294.08862.5d" @default.
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