Using the behavioral flexibility operant task to detect long-term deficits in rats following middle cerebral artery occlusion

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Abstract

Stroke is a leading cause of death and disability and currently only has one FDA approved pharmacological treatment (tissue plasminogen activator), which is only administered to a fraction of stroke patients due to contraindications. New treatments are desperately needed but most treatments fail in clinical trials, even after showing benefit in animal models of stroke. To increase the translatability of animal stroke research to humans, sensitive functional measures for both the acute and chronic stages in animal models of stroke are needed. The objective of this study was to determine the sensitivity of certain behavioral tasks, up to seven weeks following occlusion of the middle cerebral artery (MCAo) in rats. A battery of behavioral tasks, including rotorod, cylinder, and limb-placement, was conducted weekly for seven weeks. Also, a behavioral flexibility operant task was introduced at the end of the study to measure cognitive deficits. All functional outcome measures showed significant differences between stroke and control groups, indicating that these tasks are sensitive enough to detect deficits in a long-term MCAo study in rats. This provides useful information for those trying to increase translatability in their own stroke research by providing long-term sensitive testing paradigms in a relevant stroke model.

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