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22. European Stroke Conference 497 Translational stroke research Actovegin treatment initiated 6 hours after cerebral ischemia aids cognitive recovery in the rat 4-vessel occlusion model but not when initiated after 28 days. S. Meilin1, D. Muresanu2, J. Donoghue3, M. Elmlinger4 Neurology Discovery Service, MD Biosciences Ltd, Ness Ziona, ISRAEL1, Department of Neu-rosciences, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, ROMANIA2, School of Pharmacy & Biosciences, Liverpool John Moores University, Liverpool, UNITED KING-DOM3, Exploratory Translational Development, Takeda Pharmaceuticals International GmbH, Glattpark-Opfikon, SWITZERLAND4 Background Stroke and its cognitive complications are major burdens but effective regenerative treatments are lacking. Actovegin is a biological multicomponent drug with metabolic and neuroprotective effects which has been shown to improve clinical outcomes in mixed dementia and diabetic neuropathy. In hippocampal neuronal cultures it reduces apoptosis and oxidative stress. Moreover, regeneration of peripheral neurons has been shown in the STZ rat diabetic neurophathy model, in vivo. Objective To compare the effects of Actovegin in the 4-vessel occlusion rat model of global cerebral ischemia when initiated 6 hours vs. 28 days after induction of cerebral ischemia in rats. Methods After induction of cerebral ischemia, early treatment cohort (ETC) rats were treated with Actovegin or placebo (started 6 hours post ischemia) on study days 1-40; late treatment cohort (LTC) rats were treated with Actovegin or placebo on days 28-67. On day 36, ETC rats underwent a water maze test (WMT) to assess learning and memory: twice daily for 4 days, they were put in a water pool with a hidden platform for 60 seconds or until they found the platform (learning task); on the 5th day the platform was removed and the rat put once in the pool for 60 seconds. The time spent in the quad-rant where the platform had been located was recorded (memory). LTC rats started the WMT on day 24. Both cohorts repeated the WMT on day 64. Results In the ETC, in both the first and final WMT, Actovegin treatment improved both learning (p<0.05) and memory (p<0.05) vs placebo. In the LTC, there were no differences between the Actovegin and placebo groups in mean learning times (longer on study day 64 than on day 27) or in the final mem-ory 552 © 2013 S. Karger AG, Basel Scientific Programme test. Conclusions Actovegin treatment when started 6 hours post ischemia but not 28 days post ischemia improved learning and memory indicating a neuroprotective effect from early treatment. This finding confirms the importance of early Actovegin administration post ischemia. 498 Translational stroke research Endothelin-1 in cephalic and peripheral venous blood in acute ischemic stroke patients C. Back1, O. Mathiesen2, K.L. Kerstin Lipka Thiesen3, K. Skovgaard4, N.A. Pedersen5, L. Edvins-son6, P. Bie7, N.J. Aachmann-Andersen8, V.A. Larsen9, H.K. Iversen10 Translational Stroke Center, Department of Neurology Copenhagen University Hospital Glostrup, Glostrup, DENMARK1, Department of Anaesthesiology, Copenhagen University Hos-pital Glostrup, Glostrup, DENMARK2, Department of Anaesthesiology, Copenhagen University Hospital Glostrup, Glostrup, DENMARK3, Department of Anaesthesiology, Copenhagen University Hospital Glostrup, Glostrup, DENMARK4, Department of Anaesthesiology, Copenhagen University Hospital Glostrup, Glostrup, DENMARK5, Translational Stroke Center, Glostrup Research Institute, Copenhagen University Hospital Glostrup, Glostrup, DENMARK6, 5Institute of Molecular Med-icine, University of Southern Denmark, Odense, DENMARK7, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, DENMARK8, Department of Radiology, Copenhagen University Hospital Glostrup, Glostrup, DENMARK9, Translational Stroke Center, Department of Neurology Copenhagen University Hospital Glostrup, Glostrup, DENMARK10 Background Endothelin 1 (ET-1) is a potent vasoconstrictor, produced primarily by endothelial cells. Antagonism of ET-1 decreases experimental infarct size in rodent animal stroke models and endothelin receptor expression is increased in animal stroke models and in post-mortem samples of the middle cerebral artery from ischemic stroke patients. In acute stroke patients, measurements of circulating ET-1 lev-els show conflicting results. In the present study we investigated local ET-1 levels in the jugular and peripheral venous blood in acute ischemic stroke patients and in healthy subjects. Methods 16 patients 70 years old (65 – 80 yrs), M:F 10:6) suffering acute ischemic stroke within the last 48 hours and 10 healthy male controls, age: 25 years old (23 – 29 yrs) were included. In patients plas-ma ET-1 from the external jugular vein (n = 6) and the internal jugular bulb (n = 10) was compared to cubital venous levels in the acute and post-stroke phase (> 4 months after onset). Results In the acute phase ET-1 levels in jugular venous blood (external and internal) were lower than corre-sponding peripheral levels, 0.80 (0.58 - 1.55) pmol/ml versus 1.15 (0.93 - 1.53) pmol/ml (p < 0.05). No differences were found in the healthy control group, 1.57 (0.48 - 2.22) pmol/ml versus 1.27 (0.85 - 2.04) pmol/ml (ns). The jugular-peripheral vein differences were significantly larger in stroke pa-tients than in healthy controls. Conclusion The results show that in patients suffering acute ischemic stroke the ET-1 level in jugular blood is lower than in peripheral blood. This may be due to enhanced ET-1 receptor expression in the infarct-ed area reflecting vascular plasticity. This emphasizes that peripheral measurements cannot be used as expression for local production or turnover in the brain circulation. Knowledge of the exact role and temporal course of the ET receptor regulations could expose alternative pathways to neuropro-tective treatments.


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