期刊
THROMBOLYSIS AND ACUTE STROKE TREATMENT: PREPARING FOR THE NEXT DECADE
卷 1268, 期 -, 页码 95-107出版社
BLACKWELL SCIENCE PUBL
DOI: 10.1111/j.1749-6632.2012.06705.x
关键词
rt-PA; Sur1; glyburide; MMP-9; cerebral ischemia; stroke
资金
- NHLBI NIH HHS [R01 HL082517] Funding Source: Medline
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.
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