The Feasibility Of Modelling Stroke In Aged Obese Rats

Introduction: Nearly 75% of strokes occur in people over 65 often having co-morbidities such as hypertension (1) and metabolic disarrangement (2). Despite this most animal models use young and healthy rodents with poor resultant predictive validity (3). This study examines the feasibility of modelling stroke in aged, obese rats to better reflect the clinical situation.

Methods: 12 month old male Wistar-Han rats (500-650g, n=15) were fed a high fat diet containing 60% fat for 8 months. To assess the development of metabolic syndrome blood samples were collected every month and analysed using ELISAs. At 20 months old animals underwent middle cerebral artery occlusion (MCAO, 4) alongside the 6 month old controls (n=10) normally used in stroke research to test the feasibility of using aged obese animals in this research. A subset of the aged animals underwent MCAO first to determine the ideal occlusion duration. Survival, weight and functional outcome in aged and control animals was monitored for 4 weeks 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=0.13, unpaired t test). Blood analysis showed increased c-peptide (p=0.0062, unpaired t test), leptin (p=0.0003, unpaired t test) 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. Infarcts were similar in size to control animals (mean: 246.2±70.58mm3 vs 207.8±65.40mm3, p=0.7024, unpaired t test). Vessel histology did not reveal any fatty deposits in aged or control animals.

Conclusions: 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.

Acknowledgements: This study was funded by the BPS.

References:

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