Abstracts

Rationale: Post-stroke epilepsy represents 11 % of all epilepsy and 22%of all cases of status epilepticus (Camilo 2004; De Lorenzo 1996; Herman 2002). Animal models of stroke-induced epilepsy are potentially useful to study the temporal evolution of acquired epilepsy and to identify the molecular and cellular mechanism underlying epileptogenesis. In the present study we investigate phenomena of hyperexcitability in a new in vitro model of focal ischemia in which the preservation of the tridimensional connections between close and remote brain areas are maintained. In particular we assessed if i) acute alterations induced by focal ischemia are associated with changes in synaptic excitability and ii) enhanced excitatory networks would lead to abnormal epileptiform activity. Methods: Permanent focal ischemia was induced by the occlusion of either the anterior cerebral arteries (ACAs) or one of the rostral posterior cerebral arteries (rPCA) was performed in the isolated guinea pig brain maintained in vitro by arterial perfusion Results: Simultaneous extracellular recordings performed with multiple electrodes positioned in brain areas within and outside the vascular territory of the occluded vessels revealed transient ischemic depolarizations (ID) exclusively in the core territories involved by the ischemic insult. The propagation and spatial distribution of IDs observed in the ischemic area strictly correlated to the ischemia-induced tissue damage successively defined by immuno-histochemical analysis with antibodies anti- mictotubule-associate protein (MAP-2) and by MRI analysis. In particular, TrD maps demonstrated areas of hypointensity that closely correlate to the MAP-2 negative areas (Pastori et al, 2007; 2008; Breschi et al, 2010). Phenomena of hyper excitability in the ischemic core and penumbra were analyzed by paired-pulse stimulation of the lateral olfactory tract at low and high frequency unmasked by comparing the amplitudes of mono-and di-synaptic responses between conditioning (first) and conditioned (second) paired stimuli. Conclusions: At the light of these results we demonstrated that the in vitro isolated guinea pig brain preparation is suitable to study the correlation between anatomical/MR and electrophysiological changes and to evaluate early acute alterations in excitability occurring after an ischemic insult.