• J Marc Simard, Zhihua Geng, Frank L Silver, Kevin N Sheth, W Taylor Kimberly, Barney J Stern, Mario Colucci, and Volodymyr Gerzanich.
• Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. msimard@smail.umaryland.edu
• Ann. N. Y. Acad. Sci. 2012 Sep 1;1268:95-107.

AbstractHemorrhagic transformation (HT) associated with recombinant tissue plasminogen activator (rt-PA) complicates and limits its use in stroke. Here, we provide a focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA-associated HT in cerebral ischemia, and we review emerging evidence that the selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S. adopted name, glyburide), may provide protection against rt-PA-associated HT in cerebral ischemia. Glyburide inhibits activation of MMP-9, ameliorates edema formation, swelling, and symptomatic hemorrhagic transformation, and improves preclinical outcomes in several clinically relevant models of stroke, both without and with rt-PA treatment. A retrospective clinical study comparing outcomes in diabetic patients with stroke treated with rt-PA showed that those who were previously on and were maintained on a sulfonylurea fared significantly better than those whose diabetes was managed without sulfonylureas. Inhibition of Sur1 with injectable glyburide holds promise for ameliorating rt-PA-associated HT in stroke.© 2012 New York Academy of Sciences.

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