Modelling of the ischemic penumbra

What happens to the ischemic penumbra - defined as a territory of criticall y reduced blood flow in the close neighborhood of an ischemic core - determ ines outcome after stroke. Currently the pathophysiology of the penumbra is studied predominantly in rat models with occlusion of the middle cerebral artery. Here we propose two other rat models with distinct advantages. One produces a large territory of critical flow reduction in the cortex of one hemisphere without presence of an infarct core: this model is suited to stu dy mediator mechanisms that may transform the penumbra into necrotic tissue . It is produced by occluding one carotid artery and in addition reducing a rterial pressure to 50 mm Hg using the hypobaric hypotension technique. Cor tical flow is assessed by laser Doppler scanning. The second mode involves the photochemical occlusion of two adjacent cortical Veins and goes along w ith a rather widespread reduction of cortical flow and the development of s mall infarcts of 2-5 mm(3) infarct volume. Like the first model it is suite d to administer mediators causing the infarct to grow in size, and thereby to evaluate the pathophysiologic significance of individual mediator mechan isms. In addition the model can be used to study specific therapeutic appro aches.