Does inhibiting Sur1 complement rt-PA in cerebral ischemia?
Article first published online: 20 SEP 2012
© 2012 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1268, Thrombolysis and Acute Stroke Treatment pages 95–107, September 2012
How to Cite
Simard, J. M., Geng, Z., Silver, F. L., Sheth, K. N., Kimberly, W. T., Stern, B. J., Colucci, M. and Gerzanich, V. (2012), Does inhibiting Sur1 complement rt-PA in cerebral ischemia?. Annals of the New York Academy of Sciences, 1268: 95–107. doi: 10.1111/j.1749-6632.2012.06705.x
- Issue published online: 20 SEP 2012
- Article first published online: 20 SEP 2012
- cerebral ischemia;
Hemorrhagic 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.