Ischemic Injury Does Not Stimulate Striatal Neuron Replacement Even during Periods of Active Striatal Neurogenesis

Ischemic damage to the adult rodent forebrain has been widely used as a model system to study injury-induced neurogenesis, resulting in contradictory reports regarding the capacity of the postnatal brain to replace striatal projection neurons. Here we used a software-assisted, confocal approach to survey thousands of cells generated after striatal ischemic injury in rats and showed that injury fails not only to stimulate production of new striatal projection neurons in the adult brain but also to do so in the neonatal brain at early postnatal ages not previously explored. Conceptually this is significant, because it shows that even during periods of active striatal neurogenesis, injury is not a sufficient stimulus to promote replacement of these neurons. Understanding the intrinsic capacity of the postnatal brain to replace neurons in response to injury is fundamental to the development of "self-repair" therapies.