Cellular and molecular events underlying the dysregulated response of the aged brain to stroke: a mini-review

Abstract

Background: Age-related brain injuries, including stroke, are a major cause of physical and mental disabilities.

Objective: Therefore, studying the basic mechanism underlying functional recovery after brain stroke in aged subjects is of considerable clinical interest.

Methods: This review summarizes the effects of age on recovery after stroke in an animal model, with emphasis on the underlying cellular mechanisms.

Results: Data from our laboratory and elsewhere indicate that, behaviorally, aged rats were more severely impaired by stroke than young rats, and they also showed diminished functional recovery. Infarct volume did not differ significantly between young and aged animals, but critical differences were apparent in the cytological response to stroke, most notably an age-related acceleration in the development of the glial scar. Early infarct in older rats is associated with premature accumulation of BrdU-positive microglia and astrocytes, persistence of activated oligodendrocytes, a high incidence of neuronal degeneration and accelerated apoptosis. In aged rats, neuroepithelial-positive cells were rapidly incorporated into the glial scar, but these neuroepithelial-like cells did not make a significant contribution to neurogenesis in the infarcted cortex in young or aged animals. The response of plasticity-associated proteins like MAP1B, was delayed in aged rats. Tissue recovery was further delayed by an age-related increase in the amount of the neurotoxic C-terminal fragment of the beta-amyloid precursor protein (A-beta) at 2 weeks poststroke.

Conclusion: The available evidence indicates that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis for this phenomenon in the aging brain could yield novel approaches to neurorestoration in the elderly.