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Characterisation of ischaemic stroke in diet-induced obese rats

Pipe, Rachel-Anne Lucy

[Thesis]. Manchester, UK: The University of Manchester; 2016.

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Abstract

Stroke is a leading cause of death and disability. Obesity predisposes the risk of ischaemic stroke and is associated with poorer stroke prognosis. The mechanisms by which obesity increases ischaemic damage are not well understood. However, co-morbidities that share common features with obesity have been shown to exacerbate stroke damage due to deficits in cerebral blood flow (CBF) after stroke. This suggests a similar mechanism may exist in obesity.The long term aim of work stemming from this project will be to investigate whether obesity exacerbates ischaemic stroke damage due to deficits in cerebral perfusion. Therefore, the current MPhil project aims to establish and characterise a rat model of diet-induced obesity (DIO) and assess the effect of the diet model on ischaemic strokeMale Wistar rats were fed either a control or high fat diet (HFD) for 12 weeks then stroke was induced by 60 min middle cerebral artery occlusion (MCAo) followed by 4, 24 or 48 h reperfusion. Lesion volumes were analysed histologically or by diffusion weighted magnetic resonance imaging.HFD rats were divided into diet induced obese (DIO) and DIO-resistant (DIO-R) groups dependent on their weight gain relative to controls. Defined this way, DIO rats had greater body mass and body fat content than controls. Unexpectedly, stroke surgery failed to produce lesions in many animals. The poor stroke surgery success rate resulted in very low animal numbers meaning definitive conclusions regarding the effect of obesity on stroke could not be drawn. However, preliminary data from one cohort of rats suggests that DIO rats may experience poorer outcome from ischaemic stroke based on lesion volume and behavioural scores.We conclude that the animal models developed in the current study require further work to enable future studies into the effect of obesity on CBF following stroke. Understanding the relationship between obesity and enhanced ischaemic damage remains an important avenue of research which will aid future development of treatments for this subtype of stroke patients.