Translational Research

Abstract

Introduction: Nearly 75% of strokes occur in people over 65 often having co-morbidities such as hypertension and metabolic disarrangement. Despite this, most animal models use young and healthy rodents with poor resultant predictive validity. This study examines the feasibility of modelling stroke in aged, obese rats to better reflect the clinical situation. Method: 12 month old Wistar-Han rats (500-650g, n = 15) were fed a high fat diet containing 60% fat for 8 months. Serial blood samples were taken to assess the development of metabolic syndrome. Some animals were used to determine the optimal occlusion duration of the middle cerebral artery to model ischaemic stroke. Remaining rats underwent this optimised procedure alongside 6-month old controls (n = 10). Survival, weight and functional outcome were monitored post-stroke. Blood vessels collected at termination were assessed for fatty deposits. Results: In the 8 months prior to surgery rats gained a large amount of weight (750-1050g). Obese animals did not become significantly hypertensive (p = 0.79). Blood analysis showed increased C-peptide (p = 0.005), leptin (p = 0.006) and an altered inflammatory response (Eotaxin, IL-4 and RANTES). 30 minutes was determined to be the optimal occlusion length in this model. Survival and functional deficits did not significantly differ from control animals. Full analysis of infarct volumes and vessel histology is ongoing. Discussion: While modifications were required to provide the optimal care for these rats (including restraint, housing density and during surgery heating), this more translational, aged obese model may give a better prediction of therapeutic outcome in stroke research.