Abstract

Background:Stroke is a devastating neurological injury, which can result in significant cognitive and behavioural deficits. Modelling the disease processes associated with stroke in animals is key to the development of novel therapeutic approaches. However, some aspects of stroke pathophysiology, including neuropsychiatric symptoms, do not translate well from humans to animals. Here, we aimed to investigate the development of post-stroke depression in a rodent model of stroke.Methods:The distal middle cerebral artery (MCA) was permanently occluded by electrocoagulation in adult male C57/Bl6/J mice. Animals were allowed to survive for 6 hours, 24 hours, 2 days, 5 days or 7 days prior to behavioural testing. Brains were taken to confirm lesion volumes at the above times. Behavioural tests studied basic exploration and motivation (open field and marble burying) as well as depression-like behaviours (tail suspension and sucrose preference).Results:Animals developed robust and reproducible lesions in the cortex but whilst stroke reduced activity in the open field, animals showed no associated behavioural deficits in any of the tests used for depression-like behaviours.Conclusions:The distal middle cerebral artery occlusion (MCAO) model results in a small cortical lesion which produces no depression-like behaviours. These negative data are important for those wishing to investigate the more cognitive and behavioural aspects of stroke.

Highlights

  • Major depression is an important neuropsychiatric consequence of stroke, and develops in approximately one third of stroke patients, often independent of functional deficits1,2

  • Distal permanent model of MCAO (pMCAO) animals showed a variation in infarct volumes over the time course, peaking at 24 hours (Figure 1A) with the infarct being restricted to the cortex at all time points

  • Weight loss in pMCAO animals was higher overall than sham animals (Figure 1B; two-way analysis of variance (ANOVA); p

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Summary

Introduction

Major depression is an important neuropsychiatric consequence of stroke, and develops in approximately one third of stroke patients, often independent of functional deficits. Rodent models of post-stroke depression often combine middle cerebral artery occlusion (MCAO) models with models of chronic stress3 Whilst this results in a semi-reproducible set of animals showing both lesions and depression-like behaviours, it is not necessarily representative of the human condition. Results: Animals developed robust and reproducible lesions in the cortex but whilst stroke reduced activity in the open field, animals showed no associated behavioural deficits in any of the tests used for depression-like behaviours. Conclusions: The distal middle cerebral artery occlusion (MCAO) model results in a small cortical lesion which produces no depression-like behaviours. These negative data are important for those wishing to investigate the more cognitive and behavioural aspects of stroke

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