Effect of sex and age interactions on functional outcome after stroke

Stroke is one of the leading causes of death and disability worldwide. Experimental and clinical studies showed that sex and age play an important role in deciding the outcome after stroke. At younger ages, males were shown to have a higher risk for stroke than females. However, this trend reverses in older ages particularly when females reach menopause. Many preclinical studies indicate that steroid hormones modulate the age-dependent differential stroke outcome. In addition, patterns of cell death pathways activated following cerebral ischemia are distinct between males and females, but independent of steroid hormones. Recent studies also indicate that microRNAs play important roles in mediating sex-specific stroke outcome by regulating stroke-related genes. This review discusses the contribution of sex and age to outcome after stroke with particular emphasis on the experimental studies that examined the effects of steroid hormones, differential cell death pathways, and involvement of sex-specific microRNAs following cerebral ischemia. Current understanding of the role of thrombolytic agents in stroke therapy is also discussed.