A pilot of the feasibility and usefulness of an aged obese model for use in stroke research

Learoyd, Annastazia E.; Calmus, Ryan; Cunningham, Chelsea N.; England, Tim J.; Farr, Tracy D.; Fone, Kevin C.F.; Kendall, David A.; O�Sullivan, Saoirse E.; Trueman, Rebecca C.

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.

Citation

Learoyd, A. E., Calmus, R., Cunningham, C. N., England, T. J., Farr, T. D., Fone, K. C., Kendall, D. A., O’Sullivan, S. E., & Trueman, R. C. (2021). A pilot of the feasibility and usefulness of an aged obese model for use in stroke research. Wellcome Open Research, 6, Article 104. https://doi.org/10.12688/wellcomeopenres.16592.1

• Journal Article Type: Article
• Acceptance Date: Apr 27, 2021
• Online Publication Date: May 10, 2021
• Publication Date: May 10, 2021
• Deposit Date: Nov 30, 2021
• Publicly Available Date: Nov 30, 2021
• Journal: Wellcome Open Research
• Electronic ISSN: 2398-502X
• Publisher: F1000Research
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Article Number: 104
• DOI: https://doi.org/10.12688/wellcomeopenres.16592.1
• Public URL: https://nottingham-repository.worktribe.com/output/5531050
• Publisher URL: https://wellcomeopenresearch.org/articles/6-104/v1
• Additional Information: Referee status: Awaiting Peer Review; Grant Information: This work was supported by the Wellcome Trust [204843/z/16/z]; a British Pharmacology Society IPF Pump Priming Grant; and the Biotechnology and Biological Sciences Research Council [BB/F016956/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Copyright: This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.