Does inhibiting Sur1 complement rt-PA in cerebral ischemia?
Ann N Y Acad Sci
; 1268: 95-107, 2012 Sep.
Article
in En
| MEDLINE
| ID: mdl-22994227
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Drug
/
Brain Ischemia
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Glyburide
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Tissue Plasminogen Activator
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ATP-Binding Cassette Transporters
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Matrix Metalloproteinase 9
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Potassium Channels, Inwardly Rectifying
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Diabetes Mellitus, Type 2
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Hypoglycemic Agents
/
Antioxidants
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Language:
En
Journal:
Ann N Y Acad Sci
Year:
2012
Document type:
Article
Affiliation country: