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Stroke. 2014 Mar;45(3):896-9. doi: 10.1161/STROKEAHA.113.004488. Epub 2014 Jan 28.

Direct thrombin inhibitor argatroban reduces stroke damage in 2 different models.

Author information

1
From the Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA.

Abstract

BACKGROUND AND PURPOSE:

We showed previously robust neuroprotection with the thrombin inhibitor argatroban and now sought additional support for its neuroprotective potential.

METHODS:

We used behavioral and histological end points; rigorously blinded the study groups; extended the treatment window to 3 hours after ischemia onset; and used 2 separate models. First, 2-hour filament middle cerebral artery occlusion in 64 male Sprague-Dawley rats was followed by learning and memory testing and quantitative histomorphometry. Randomly assigned treatment was 0.45 mg argatroban, saline, or 0.4 U thrombin. Second, we used the quantal bioassay (n=272) after 2-hour middle cerebral artery occlusion to detect the longest time delay after which therapy failed.

RESULTS:

Argatroban powerfully and significantly reversed learning and memory deficits because of focal ischemia compared with saline or thrombin (P<0.03; ANOVA). Argatroban was significantly (P<0.05; t test with Bonferroni) protective when given immediately or after 1, 2, 3, but not 4 hours delay.

CONCLUSIONS:

We obtained supportive evidence for argatroban protection of the neurovascular unit using behavioral and histological measurements at realistic therapeutic time windows.

KEYWORDS:

models, animal; stroke; thrombin; treatment outcome

PMID:
24473182
PMCID:
PMC3995814
DOI:
10.1161/STROKEAHA.113.004488
[Indexed for MEDLINE]
Free PMC Article
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