26 Neurogenesis following Stroke Affecting the Adult Brain

Abstract

Stroke is caused by occlusion of a cerebral artery, which gives rise to focal ischemia with irreversible injury in a core region and partially reversible damage in the surrounding penumbra zone. In another type of insult, abrupt and near-total interruption of cerebral blood flow as a consequence of cardiac arrest or coronary artery occlusion leads to global ischemia and selective death of certain vulnerable neuronal populations such as the pyramidal neurons of hippocampal CA1. During the last decade, these ischemic insults have been reported to induce the formation of new neurons in the adult rodent brain from neural stem cells (NSCs) located in two regions: the subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG). Ischemia-induced neurogenesis is triggered both in areas where new neurons are normally formed, such as the DG, and in areas that are nonneurogenic in the intact brain, e.g., the striatum. These findings have raised several important issues: (1) Is the evidence for the formation of new neurons really solid or could there be other interpretations such as aberrant DNA synthesis caused by the ischemic insult in already existing, mature neurons? (2) What are the functional consequences of ischemia-induced neurogenesis? (3) Because the neurogenic response is minor and recovery after stroke incomplete, how can this presumed self-repair mechanism be boosted? In this chapter, we summarize the current status of research on neurogenesis after stroke. We also discuss the basic scientific problems that need to be addressed before this...