Abstract W MP37: A Novel Homocysteine Inhibitor Enhances Neurological Recovery after Cerebral Ischemia in Mice and Non-Human Primates

Background: Hyperhomocyteinemia is associated with cardiovascular and cerebrovascular diseases. Many studies have investigated the deleterious effects of intercellular homocysteine (Hcy) accumulation on vascular and brain tissue. AEB-577 is a potent Hcy synthesis inhibitor based on a non-adenosine analog. We hypothesized that AEB-577 could normalize Hcy content in brain tissue, reduce cytotoxicity of Hcy and ameliorate neurological dysfunction after stroke. Method: Male C57BL/6N mice were subjected to photochemically induced thrombosis, and treated orally with AEB-577 (1, 3, 10 mg/kg) or vehicle 10 minutes after the infarction. Infarct volume was assessed by tetrazolium staining and motor incoordination was evaluated using rota-rod test at 24 hours after infarction. In the second experiment, Hcy content in peri-infarct area was measured at 3 days after infarction by HPLC. In a non-human primate experiment, male cynomolgus monkeys were subjected to permanent middle artery occlusion (pMCAO), and divided int...