Perturbed cellular response to brain injury during aging.

Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are only partly understood. Therefore, studying the basic mechanisms underlying structural and functional recovery after brain injury in aged subjects is of considerable clinical interest. Behavioral and cytological analyses of rodents that have undergone experimental injury show that: (a) behaviorally, aged rodents are more severely impaired by ischemia than are young animals, and older rodents also show diminished functional recovery; (b) compared to young animals, aged animals develop a larger infarct area, as well as a necrotic zone characterized by a higher rate of cellular degeneration and a larger number of apoptotic cells; (c) both astrocytes and macrophages are activated strongly and early following stroke in aged rodents; (d) in older animals, the premature, intense cytoproliferative activity following brain injury leads to the precipitous formation of growth-inhibiting scar tissue, a phenomenon amplified by the persistent expression of neurotoxic factors; (e) though the timing is altered, the regenerative capability of the brain is largely preserved in rats, at least into early old age. Whether endogenous neurogenesis contributes to spontaneous recovery after stroke has not yet been established. If neurogenesis from endogenous neuronal stem cells is to be used therapeutically, an individual approach will be required to assess the possible extent of neurogenic response as well as the possibilities to alter this response for functional improvement or prevention of further loss of brain function.