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22. European Stroke Conference 16:30-18:00 Oral Session Room 17 Experimental Studies B Chairs: M. Endres, Germany and D. Vivien, France 10 Experimental studies B 16:30 - 16:40 Neuronal damage in mild ischaemia: synaptic failure? J. Hofmeijer1, A.T.B. Mulder2, M.J.A.M. van Putten3, J. le Feber4 University of Twente and Rijnstate Hospital, Enschede, THE NETHERLANDS1,Uni-versity of Twente, Enschede, THE NETHERLANDS2, University of Twente, Enschede, THE NETHERLANDS3, University of Twente, Enschede, THE NETHERLANDS4 Background Chronic mild cerebral ischaemia and hypoxemia result from prevalent diseases, such as chronic heart failure or obstructive pulmonary disease. 80% of these patients have cog-nitive impairment. Despite its high prevalence, the nature of neuronal damage is unclear, since, unlike acute cerebral ischaemia, structural neuronal changes as visualized by MRI are lacking. Several observations point to a disturbed synaptic connectivity. These include the pattern of cognitive decline, dominated by disturbances of learning and memory, which indeed strongly depend on synaptic integrity, and experimental observations of isolated persistent synaptic fail-ure after transient acute hypoxia under in vitro conditions. Cultured neuronal networks are an established in vitro model enabling to study synaptic connectivity and neuronal viability during mild to moderate hypoxia. Methods 14 cultured networks of rat cortical neurons grown over a multi electrode array were exposed to moderate hypoxia (oxygen concentration of 230μM low-ered to 80μM) during three (n=7) or six (n=7) hours. Synaptic functioning was assessed before, during and after hypoxia by the amount of spontaneous network activity and network responses to electrical stimulation. Action potential shapes and direct (non-synaptic) stimulus respons-es were used as measures of neuronal membrane integrity. Results During hypoxia array wide firing rate decreased by ~60% (fig 1) and synapticly mediated responses after electrical stimu-lation disappeared (fig 2), whereas direct responses (fig 2) and the shapes of action potentials remained unchanged. Neurons were microscopically undamaged. Conclusion In cultured neuronal networks, moderate hypoxia during three or six hours causes synaptic disturbances without structural or functional damage to individual neurons. In chronic mild cerebral ischemia or hypoxemia, synaptic failure may play a role in the emergence of cog-nitive impairment. 78 © 2013 S. Karger AG, Basel Scientific Programme


Karger_ESC London_2013
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