A fundamental feature of the adult mammalian brain is its inability to regenerate after injury. Considerable effort has gone into examining the changes that occur in the brain after injury and to examine the extent to which these changes may affect the brain's regenerative capacity. Towards this end, I have studied cellular proliferation in the adult brain in two settings;​ (1) after injury to the CNS when massive proliferation ensues as normally quiescent cells are induced to proliferate and (2) under baseline conditions when mitotically active cells are found in the subependyma in the forebrain.

I examined the time course of the gliotic response that results from an excitotoxic lesion into the striatum of the adult mouse. I found that microglia are one of the key resident brain cells contributions to the proliferative response. Mononuclear phagocytes derived from the blood share many common features with the brain macrophage (microglia) causing confusion regarding their relative contributions and making it important to consider them separately. To delineate their separate roles in the proliferative response bone marrow chimeric animals were used. Donor blood cells contain multiple copies of a beta-globin gene insert can be unequivocally identified using in situ hybridization. While blood cells infiltrate the damaged brain through the broken blood-brain-barrier after injury, their contribution to the proliferative response is indirect through activation of the microglia. The blood cells make only a very minor contribution to the proliferating population.

The subependyma lining the lateral ventricles in the adult forebrain was found to contain a population of constitutively proliferating cells (up to 3% of the subependymal population) which undergo steady-state division and have a cell cycle time of 12.7 hours. As well, the subependyma contains relatively quiescent cells with the capacity to self-renew and differentiate into neurons and glia in vitro. Given that one of the key reasons for lack of regeneration in adult nervous tissue is the inability to replace lost or dying neurons, this endogenous population of neural stem cells within the subependyma suggests that the adult brain may retain an inherent capacity to regenerate.