期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 25, 期 1, 页码 87-97出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/sj.jcbfm.9600010
关键词
embolic stroke; glycoprotein GP IIb/IIIa receptor inhibitor; magnetic resonance imaging (MRI); platelet; recombinant tissue plasminogen activator (r-tPA)
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL064766] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS023393, R01NS038292, R01NS043324] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL64766] Funding Source: Medline
- NINDS NIH HHS [P01 NS23393, R01 NS38292, R01 NS43324] Funding Source: Medline
Suppression of platelet activation improves the efficacy of thrombolytic therapy for stroke. Thus, combination treatment with recombinant tissue plasminogen activator (r-tPA) and 7E3 F(ab')(2), a GPIIb/IIIa inhibitor that binds the platelet to fibrin, may improve the efficacy of thrombolytic therapy in embolic stroke. Magnetic resonance imaging (MRI) was used to monitor treatment response in rats subjected to embolic middle cerebral artery (MCA) occlusion (MCAo). Animals were randomized into treated (n = 12) and control (n = 10) groups and received intravenous combination therapy or saline, respectively, 4 hours after MCAo. Magnetic resonance imaging (MRI) measurements performed 1 hour after MCAo showed no difference between groups. However, an increased incidence (50%) of MCA recanalization was found in the treated group at 24 hours compared with 20% in the control group. The area of low cerebral blood flow at 24 and 48 hours was significantly smaller in the combination treatment group, and the lesion size, as indicated from the T-2 and T-1 maps, differed significantly between groups. Fluorescence microscopy measurements of cerebral microvessels perfused with fluorescein isothiocyanate-dextran and measurements of infarct volume revealed that the combination treatment significantly increased microvascular patency and reduced infarct volume, respectively, compared with the control rats. The efficacy of combination treatment 4 hours after ischemia is reflected by MRI indices of tissue perfusion, MCA recanalization, and reduction of lesion volume. The treatment also reduced secondary microvascular perfusion deficits.
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