Pharmacological Inhibition of Phospholipase D Protects Mice From Occlusive Thrombus Formation and Ischemic Stroke—Brief Report

• DOI: 10.1161/atvbaha.113.302030
• Publication Date: 2013-07-19T04:54:32Z
• Authors: David Stegner; Ina Thielmann; Peter Kraft; Michael A. Frohman; Guido Stoll; Bernhard Nieswandt
• Keywords: Stroke; Penumbra

We recently showed that mice lacking the lipid signaling enzyme phospholipase (PL) D1 or both PLD isoforms (PLD1 and PLD2) were protected from pathological thrombus formation ischemic stroke, whereas hemostasis was not impaired in these animals. sought to assess whether pharmacological inhibition of activity affects hemostasis, thrombosis, thrombo-inflammatory brain infarction mice.Treatment platelets with reversible, small molecule inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), led a specific blockade associated reduced α-granule release integrin activation. Mice received FIPI at dose 3 mg/kg displayed occlusive upon chemical injury carotid arteries mesenterial arterioles. Similarly, FIPI-treated had smaller infarct sizes significantly better motor neurological function 24 hours after transient middle cerebral artery occlusion. This protective effect major intracerebral hemorrhage prolonged tail bleeding times.These results provide first evidence might safe therapeutic strategy prevent arterial thrombosis stroke.