Abstract
Purpose: Aging is associated with a temporally dysregulated cellular response to ischemia as well as poor functional recovery. While environmental enrichment has been shown to improve the behavioral outcome of stroke in young animals, the effect of an enriched environment on behavioral and neuropathological recovery in aged animals is not known.
Methods: Focal cerebral ischemia was produced by electrocoagulation of the right middle cerebral artery in 3 month- and 20 month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests conducted over a period of 28 days following surgery. Brain tissue was then immunostained for proliferating astrocytes and the infarct and scar tissue volumes were measured.
Results: Aged rats showed more severe behavioral impairments and diminished functional recovery compared to young rats. Most infarcted animals had disturbances of sensorimotor function, with recovery beginning later, progressing more slowly, and reaching a lower functional endpoint in aged animals. However, the enriched environment significantly improved the rate and extent of recovery in aged animals. Correlation analysis revealed that the beneficial effect of the enriched environment on recovery, both in young and aged rats, correlated highly with a reduction in infarct size, in the number of proliferating astrocytes, and in the volume of the glial scar.
Conclusions: These results suggest that temporally modulating astrocytic proliferation and the ensuing scar formation might be a fruitful approach to improving functional recovery after stroke in aged rats.