Progesterone and cerebral ischaemia: the relevance of ageing

Cerebral stroke is a leading cause of long-term disability and a major cause of death in the developed world. The total incidence of stroke is projected to rise substantially over the next 20 years as a result of the rising elderly population. Although age is one of the most significant prognostic markers for poor outcome after stroke, very few experimental studies have been conducted in aged animals. Importantly, sex differences in both vulnerability to stroke and outcome after cerebral ischaemia have frequently been reported and attributed to the action of steroid hormones. Progesterone is a candidate neuroprotective factor for stroke, although the majority of pre-clinical studies have focused on using young, healthy adult animals. In terms of cerebral stroke, males and postmenopausal females represent the groups at highest risk of cerebral stroke and these categories can be modelled using either aged or ovariectomised female animals. In this review, we discuss the importance of conducting experimental studies in aged animals compared to young, healthy animals, as well as the impact this has on experimental outcomes. In addition, we focus on reviewing the studies that have been conducted to date examining the neuroprotective potential of progesterone in aged animals. Importantly, the limited studies that have been conducted in aged animals do lend further support to progesterone as a therapeutic option after ischaemic stroke that warrants further investigation.