Age and the Metabolic Syndrome as Risk Factors for Ischemic Stroke: Improving Preclinical Models of Ischemic Stroke

Ischemic stroke represents a leading cause of morbidity and mortality in thedeveloped world. This disabling and sometimes fatal event puts an everincreasing burden on the family members and medical professionals who care forstroke victims. Preclinical ischemic stroke research has predominantly utilizedyoung adult, healthy animals, a clear discrepancy when considering the clinicalpopulation affected by stroke. A broad spectrum of risk factors such as age,obesity, diabetes, and hypertension has been associated with an increased strokerisk. The effect of these comorbidities on both stroke pathophysiology andoutcome has not been emphasized and has been recognized as a shortcoming ofpreclinical studies. By addressing these conditions in experimental models ofischemic stroke, it may be possible to more accurately represent the clinicalscenario and improve therapeutic translation from bench-to-bedside. In thiswork, we review many of the risk factors associated with increased stroke risk,particularly as each risk factor relates to inflammation. Additionally, weexplore potential animal models that could be utilized in identifying thecontribution of these risk factors to stroke outcome. By investigating the riskfactors for stroke and how these may alter stroke pathophysiology, the presentdiscrepancies between preclinical studies and the clinical reality can bereconciled in an effort to improve therapeutic development and translation frombench-to-bedside.