Poststroke neurogenesis: emerging principles of migration and localization of immature neurons

Stroke induces proliferation of newly born neurons in the subventricular zone, migration of these immature neurons away from the SVZ, and localization within peri-infarct tissues. These 3 processes of proliferation, migration, and localization constitute distinct spatial and temporal zones within poststroke neurogenesis with distinct molecular and cell-cell signaling environments. Immature neurons migrate after stroke in close association with blood vessels and astrocytic processes, in a process that involves matrix metalloproteinases. This poststroke migration shares similar features with normal neuroblast migration in the rostral migratory stream. Immature neurons localize in the peri-infarct cortex in a neurovascular niche where neurogenesis is causally linked to angiogenesis through the vascular factors SDF-1 and angiopoietin-1. Other vascular and neuronal growth factors have also been linked to poststroke neuroblast localization in peri-infarct tissue, including erythropoietin. Most data on poststroke neurogenesis derive from laboratory rodents, which may have an abnormal or blunted degree of neurogenesis and neuroplasticity compared to normal, wild rodents. This will likely affect translational application of the principles of poststroke neurogenesis from mouse to man.