Enhanced cell death and learning deficits after a mini-stroke in aged hippocampus.

One view of the etiology of age-related pathology is that a single genetic abnormality or some other single factor causes the disorder. An alternative view is that multiple combinations of factors produce variants of pathology. For example, the occurrence of stroke increases with age and has been linked to neurodegenerative disorders like Alzheimer's disease (AD). The current experiments test the hypothesis that a vascular insult and aging are co-factors that contribute to dementia by evaluating the neuronal and functional integrity of the hippocampus following small, localized strokes induced by the potent vasoconstrictor, endothelin-1 (ET-1) in the rat model of hippocampal aging. The neurotoxic effects of a low dose of ET-1 injected into the hippocampus measured by lesion size (volumetrics) and cell death (Fluorojade-B) were amplified in aged rats. The aged rats also showed hippocampal-dependent memory deficits that were not present in young rats. Overall, our pattern of results suggest that the aged hippocampus is more vulnerable to the same insult that has little or no effect on the young hippocampus.