This Article Full Text Full Text (PDF) All Versions of this Article: 40/4/1530    most recent STROKEAHA.108.531699v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sugawara, T. Articles by Zhang, J. H. Search for Related Content PubMed PubMed Citation Articles by Sugawara, T. Articles by Zhang, J. H. Related Collections Animal models of human disease Apoptosis Thrombin Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Endothelium/vascular type/nitric oxide

(Stroke. 2009;40:1530.)
© 2009 American Heart Association, Inc.

Research Letters

Thrombin Inhibition by Argatroban Ameliorates Early Brain Injury and Improves Neurological Outcomes After Experimental Subarachnoid Hemorrhage in Rats

Takashi Sugawara, MD; Vikram Jadhav, MD, PhD; Robert Ayer, MD; Wanqiu Chen, MS; Hidenori Suzuki, MD, PhD John H. Zhang, MD, PhD

From Department of Physiology (T.S., V.J., R.A., W.C., H.S., J.H.Z.), Department of Neurosurgery (J.H.Z.), Department of Anesthesiology (J.H.Z.), Loma Linda University, Loma Linda, Calif; Section of Neurosurgery (T.S.), Department of Brain Medical Science, Division of Cognitive and Behavioral Medicine, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.

Correspondence to John H. Zhang MD, PhD, Department of Neurosurgery, Loma Linda University Medical Center, 11234 Anderson Street, Room 2562B, Loma Linda, CA 92354. E-mail johnzhang3910{at}yahoo.com

Background and Purpose— We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH).

Methods— The standard intravascular perforation model was used to produce experimental SAH in Sprague Dawley rats. Low-dose (0.3 mg/h) and high-dose (0.9 mg/h) argatroban, a direct thrombin inhibitor, were evaluated for effects on brain edema, blood–brain barrier (BBB) disruption, apoptotic cell death, inflammatory marker, and neurological outcomes after SAH.

Results— Both doses of argatroban attenuated BBB disruption; however, only high-dose was effective in lowering edema in all brain regions, reducing cell death, and inflammatory marker expression, and improving neurological outcomes.

Conclusions— Thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after SAH such as BBB disruption, brain edema, and cell death.

Key Words: argatroban • brain edema • early brain injury • subarachnoid hemorrhage • thrombin