In:
Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 2 ( 2009-02), p. 626-631
Abstract:
Background and Purpose— Intracerebral hemorrhage, induced by recombinant tissue plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct benefit from the neuroprotective drug edaravone, a free radical scavenger. We examined the mechanisms by which edaravone may help to suppress rtPA-induced brain hemorrhage. Methods— Male Wistar rats weighing 250 to 280 g were subjected to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly into 3 groups. Immediately after reperfusion, 1 group was intravenously injected with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group received no treatment. We assessed the hemorrhage volume and the activity of MMP-9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its mRNA expression, and nuclear factor-kappa B (NF-κB) activity in rtPA-stimulated human microvascular endothelial cells (HBECs). Results— The degree of hemorrhage and the level of endothelial cell–derived MMP-9 were elevated in rats treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone. In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-κB activation. Conclusions— We demonstrate that edaravone inhibits rtPA-induced cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9 expression in vivo, which is substantiated by inhibition of MMP-9 expression and NF-κB activation in HBECs. Edaravone may render thrombolytic therapy safer for the administration of rtPA in patients with ischemic stroke.
Type of Medium:
Online Resource
ISSN:
0039-2499
,
1524-4628
DOI:
10.1161/STROKEAHA.108.520262
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2009
detail.hit.zdb_id:
1467823-8
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