restorative neurogenesis. Hormonal interventions, such as progesterone, estrogen, and allopregnanolone have been examined heavily in recent decades as possible neuroprotective agents following traumatic brain injuries to reduce the inflammation response stunt neuronal death. In rodents, lacking the regenerative capacity for adult neurogenesis, the activation of stem cells following administration of α7 nicotinic acetylcholine receptor agonist, PNU-282987, has been identified in damaged retinas with follow-up work examining activation of neurogenesis in mammals after traumatic brain injury. Currently, there is no medical intervention that has passed phase-III clinical trials for use in the human population. Factors affecting Changes in old age Neurogenesis is substantially reduced in the hippocampus of aged animals, raising the possibility that it may be linked to age-related declines in hippocampal function. For example, the rate of neurogenesis in aged animals is predictive of memory. However, new born cells in aged animals are functionally integrated. Given that neurogenesis occurs throughout life, it might be expected that the hippocampus would steadily increase in size during adulthood, and that therefore the number of granule cells would be increased in aged animals. However, this is not the case, indicating that proliferation is balanced by cell death. Thus, it is not the addition of new neurons into the hippocampus that seems to be linked to hippocampal functions, but rather the rate of turnover of granule cells. Effects of exercise Scientists have shown that physical activity in the form of voluntary exercise results in an increase in the number of newborn neurons in the hippocampus of mice and rats. These and other studies have shown that learning in both species can be enhanced by physical exercise. Recent research has shown that brain-derived neurotrophic factor and insulin-like growth factor 1 are key mediators of exercise-induced neurogenesis. Exercise increases the production of BDNF, as well as the NR2B subunit of the NMDA receptor. Exercise increases the uptake of IGF-1 from the bloodstream into various brain regions, including the hippocampus. In addition, IGF-1 alters c-fos expression in the hippocampus. When IGF-1 is blocked, exercise no longer induces neurogenesis. Other research demonstrated that exercising mice that did not produce beta-endorphin, a mood-elevating hormone, had no change in neurogenesis. Yet, mice that did produce this hormone, along with exercise, exhibited an increase in newborn cells and their rate of survival. While the association between exercise-mediated neurogenesis and enhancement of learning remains unclear, this study could have strong implications in