Stroke is the fifth leading cause of mortality and the major cause of long-term disability in the United States. Epidemiological studies report sex differences in ischemic stroke occurrence, mortality and functional recovery. In younger demographics, the overall incidence of stroke is higher in men than younger women, but in the elderly population, stroke rates are higher in older women compared to age-matched men, indicating an interaction of age and sex as important modifiers of disease. The increased risk for stroke in older women is attributed to loss of ovarian hormones, principally estrogens. However, estrogen/estradiol therapy is not always neuroprotective for stroke, especially in aging populations. Age-related changes in central and peripheral immune cells and the blood–brain barrier may play a crucial role in modifying stroke outcomes and the effects of estrogens. This chapter discusses the role of estrogens as a stroke protectant in younger females in contrast to its anomalous effects in the aging brain. Furthermore, the chapter describes age-related changes in support cells in the brain and in the periphery and evaluates the evidence that age-associated inflammation underlies the switch in estrogens neuroprotective action in young females to its neurotoxic effects in older females.
Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition