Abstract
Background: Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model, and then examined the feasibility of modelling stroke in such rats. Methods: Twelve-month old male Wistar-Han rats (n=15) were fed a 60% fat diet for 8 months during which monthly serial blood samples were taken to assess the development of metabolic syndrome and pro-inflammatory markers. Following this, to pilot the suitability of these rats for undergoing surgical models of stroke, they underwent 30min of middle cerebral artery occlusion (MCAO) alongside younger controls fed a standard diet (n=10). Survival, weight and functional outcome were monitored, and blood vessels and tissues collected for analysis. Results: A high fat diet in aged rats led to substantial obesity. These rats did not develop type 2 diabetes or hypertension. There was thickening of the thoracic arterial wall and vacuole formation in the liver; but of the cytokines examined changes were not seen. MCAO surgery and behavioural assessment was possible in this model (with some caveats discussed in manuscript). Conclusions: This study shows MCAO is possible in aged, obese rats. However, this model is not ideal for recapitulating the complex comorbidities commonly seen in stroke patients.
Highlights
Stroke most commonly occurs in people over the age of 65 years and this population often has several additional comorbidities such as hypertension, diabetes or cholesterolemia1
Aged rats fed a high fat diet did not induce a robust range of inflammatory, metabolic and physiological changes
Stroke surgery and behavioural assessment were feasible in these rats, with some consideration
Summary
Stroke most commonly occurs in people over the age of 65 years and this population often has several additional comorbidities such as hypertension, diabetes or cholesterolemia. Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model, and examined the feasibility of modelling stroke in such rats. Results: A high fat diet in aged rats led to substantial obesity These rats did not develop type 2 diabetes or hypertension. Conclusions: This study shows MCAO is possible in aged, obese rats This model is not ideal for recapitulating the complex comorbidities commonly seen in stroke patients
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