Pathobiology of ischaemic stroke: an integrated view

Brain injury following transient or permanent focal cerebral ischaemia (str oke) develops from a complex series of pathophysiological events that evolv e in time and space. In this article, the relevance of excitotoxicity, peri -infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why m any clinical stroke trials have so far proved disappointing is addressed. T his article provides a framework that can be used to generate testable hypo theses and treatment strategies that are linked to the appearance of specif ic pathophysiological events within the ischaemic brain.