Adult neurogenesis and the ischemic forebrain

The recent identification of endogenous neural stem cells and persistent neuronal production in the adult brain suggests a previously unrecognized capacity for self-repair after brain injury. Neurogenesis not only continues in discrete regions of the adult mammalian brain, but new evidence also suggests that neural progenitors form new neurons that integrate into existing circuitry after certain forms of brain injury in the adult. Experimental stroke in adult rodents and primates increases neurogenesis in the persistent forebrain subventricular and hippocampal dentate gyrus germinative zones. Of greater relevance for regenerative potential, ischemic insults stimulate endogenous neural progenitors to migrate to areas of damage and form neurons in otherwise dormant forebrain regions, such as the neostriatum and hippocampal pyramidal cell layer, of the mature brain. This review summarizes the current understanding of adult neurogenesis and its regulation in vivo, and describes evidence for stroke-induced neurogenesis and neuronal replacement in the adult. Current strategies used to modify endogenous neurogenesis after ischemic brain injury also will be discussed, as well as future research directions with potential for achieving regeneration after stroke and other brain insults.