London, United Kingdom 2013 Poster Session Red Cerebrovasc Dis 2013; 35 (suppl 3)1-854 545 484 Experimental studies FINGOLIMOD REDUCES HEMORRHAGIC TRANSFORMATION ASSOCIATED WITH DELAYED TISSUE PLASMINOGEN ACTIVATOR TREATMENT IN A MOUSE THROM-BOEMBOLIC MODEL. F. Campos1, T. Qin2, J. Castillo3, J.H. Seo4, K. Arai5, E.H. Lo6, C. Waeber7 Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Uni-versitario, IDIS., Santiago de Compostela, SPAIN1, Stroke Research Laboratory, Department of Radiology, Massachusetts General Hospital., Boston, USA2, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, IDIS., Santiago de Compostela, SPAIN3, Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Mas-sachusetts General Hospital., Boston, USA4, Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital., Boston, USA5, Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital., Boston, USA6, School of Pharmacy, University College Cork., Cork, IRELAND7 Background: The sphingosine 1-phosphate receptor agonist fingolimod reduces infarct size in rodent models of stroke and enhances blood–brain barrier integrity. Based on these observations, we hy-pothesized that combination of fingolimod with tissue plasminogen activator (tPA) would reduce the risk of hemorrhagic transformation associated with delayed administration of tPA. Methods: We evaluated the effects of fingolimod in a mouse model of thromboembolic stroke, in which both the beneficial effect of reperfusion associated with early tPA treatment and hemorrhagic transformation associated with delayed administration mimic clinical observations in humans. Results: Our results demonstrate that fingolimod treatment attenuates the neurological deficit and reduces infarct volume after in situ thromboembolic occlusion of the middle cerebral artery. Com-bination of fingolimod and tPA improves the neurological outcome of the thrombolytic therapy and reduces the risk of hemorrhagic transformation associated with delayed administration of tPA. Conclusion: This study confirms the protective efficacy of fingolimod as a treatment against isch-emic stroke in another rodent model of stroke (thromboembolic occlusion), and suggests that fingo-limod could potentially be used in combination with tPA to reduce the risk of brain hemorrhage. 485 Experimental studies Neuroprotective Effect of Two-Herbs Water Extract Against Oxygen-Glucose Deprivation–In-duced Injury in PC12 Pheochromocytoma Cell C.W. CHAN1, J.W. XIAN2, W.N. LEUNG3, B.S. LAU4 The Chinese University of Hong Kong, Hong Kong, HONG-KONG1, The Chinese University of Hong Kong, Hong Kong, HONG-KONG2, The Chinese University of Hong Kong, Hong Kong, HONG-KONG3, The Chinese University of Hong Kong, Hong Kong, HONG-KONG4 Objectives Stroke is the third major cause of death in worldwide. More than 80% stroke is caused by cerebral ischemia. Tissue plasminogen activator is given to patient within 3 hours post-stroke. Such a short period of t-PA treatment require alternative therapy for cerebral ischemia. Gastrodiae Rhizoma (TM) and Uncariae Ramulus cum Uncis (GT) are the commonly prescribed Chinese herbal medicines on cerebral disorder. The study aims to investigate the treatment effect of a TCM formula which com-poses of TM and GT (TGW) on cerebral ischemia. Methods Nerve-growth factor treated PC12 cells were added with TGW and immediately subject to oxygen glucose deprivation (OGD) and followed by 16hr reoxygenation (OGD-R). The rescue of PC12 cell death by TGW extract was assessed by release of lactate dehydrogenase (LDH). The drug interac-tion of TM and GT was investigated during OGD-R. Furthermore, cell death mechanism of OGD was studied by dual staining with fluorescent Annexin V and propidium iodide, generation of ROS and activity change of superoxide dismutase (SOD), catalase (CAT), caspase-3. Results In LDH assay, TGW reduced cell death by 28%, 62%, 83% in OGD phase, also by 41%, 55%, 56% in R phase at 1, 2 and 4mg/ml, respectively. TM and GT combination is significantly reduced LDH release rather than either TM or GT. It suggested TM and GT have synergistic effect of protection against OGD-induced on PC12 cells. In flow cytometry, TGW treatment reduced late apoptotic and necrotic cells. OGD-induced cell injury resulted in a significant increase in intracellular ROS while TGW suppressed ROS generation. It was found that SOD, CAT and Caspase-3 activities are significantly increased after OGD. Both caspase-3 and SOD activity increased further but CAT activity dropped to same level of control group after addition of TGW. Conclusion The water extract of Tianma-Gouteng formula exhibited neuroprotective effect on nerve-growth fac-tor treated PC12 under oxygen-glucose deprivation.
Karger_ESC London_2013
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