DOI: 10.1161/01.str.31.6.1402. Integrin α <sub>IIb</sub> β <sub>3</sub> Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia

Integrin α IIb β 3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia

10.1161/01.str.31.6.1402

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

Background and Purpose —Platelets become activated and accumulate in brain microvessels of the ischemic microvascular bed after experimental focal cerebral ischemia. The binding of glycoprotein IIb/IIIa (integrin α IIb β 3 ) on platelets to fibrinogen is the terminal step in platelet adhesion and aggregation. This study tests the hypothesis that inhibition of platelet-fibrin(ogen) interactions may prevent microvascular occlusion after experimental middle cerebral artery occlusion (MCA:O). Methods —TP9201 is a novel Arg-Gly-Asp (RGD)-containing integrin α IIb β 3 inhibitor. Microvascular patency after 3-hour MCA:O and 1-hour reperfusion within the ischemic and nonischemic basal ganglia was compared in adolescent male baboons who received high-dose TP9201 (group A: IC 80 in heparin, n=4), low-dose TP9201 (group B: IC 30 in heparin, n=4), or no treatment (group C: n=4) before MCA:O. Results —After MCA:O, microvascular patency decreased significantly in group C. However, in the ischemic zones of groups A and B compared with group C, patencies were significantly greater in the 4.0- to 7.5-μm-diameter (capillary) and 7.5- to 30.0-μm-diameter vessels (2 P <0.05). A dose-dependent increase in hemorrhagic transformation was seen in group A (3 of 4 animals) compared with group B (1 of 4 animals), and no hemorrhage was visible in group C (χ 2 analysis for trend, P <0.05). Conclusions —Platelet activation contributes significantly to ischemic microvascular occlusion. Occlusion formation may be prevented by this RGD–integrin α IIb β 3 inhibitor at a dose that does not produce clinically significant parenchymal hemorrhage. The effect of microvascular patency on neuron recovery can now be tested.

Bibliography

Abumiya, T., Fitridge, R., Mazur, C., Copeland, B. R., Koziol, J. A., Tschopp, J. F., Pierschbacher, M. D., & del Zoppo, G. J. (2000). Integrin Î± IIb Î² 3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia. Stroke, 31(6), 1402â1410.

Authors 8

Takeo Abumiya (first)
Robert Fitridge (additional)
Curt Mazur (additional)
Brian R. Copeland (additional)
James A. Koziol (additional)
Juerg F. Tschopp (additional)
Michael D. Pierschbacher (additional)
Gregory J. del Zoppo (additional)

References 52 Referenced 105

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Plow EF, Ginsberg MH. Cellular adhesion: GPIIb/IIIa as a prototype adhesion receptor. Prog Hemost Thromb. 1988;8:117–156. / Prog Hemost Thromb (1988)
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Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 6:05 p.m.)
Indexed	4 days, 23 hours ago (Aug. 24, 2025, 7:08 p.m.)
Issued	25 years, 2 months ago (June 1, 2000)
Published	25 years, 2 months ago (June 1, 2000)
Published Print	25 years, 2 months ago (June 1, 2000)

Funders 0

None

BibTeX

@article{Abumiya_2000, title={Integrin α IIb β 3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia}, volume={31}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.31.6.1402}, DOI={10.1161/01.str.31.6.1402}, number={6}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Abumiya, Takeo and Fitridge, Robert and Mazur, Curt and Copeland, Brian R. and Koziol, James A. and Tschopp, Juerg F. and Pierschbacher, Michael D. and del Zoppo, Gregory J.}, year={2000}, month=jun, pages={1402–1410} }

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