An improved post-operative care protocol allows detection of long-term functional deficits following MCAo surgery in rats

Abstract

Developing new therapeutants for stroke requires animal models in which typical stroke outcomes can be detected. In rats, temporary occlusion of the middle cerebral artery (MCAo) closely resembles reversible human ischemic stroke, but most neuroprotection studies have used limited, short-term (1-2 weeks) behavioural and histological endpoints in this model. Further, the use of this model for assessing long-term recovery has been questioned. Long-term deficits may be difficult to detect because testing may not reflect the diversity of functional outcomes in clinical stroke, and/or high mortality rates mean that only the least severely affected rats remain to be tested. We believe that enhanced survival through intensive post-operative husbandry practices, and extensive behavioural testing that reflects multiple clinically relevant behavioural endpoints, will permit the detection of long-term functional deficits. In the present study, male SD rats (280-320 g) received transient (90 min) MCAo (n = 19) or sham surgery (n = 13). An intense post-operative care protocol was maintained, and assessments included various physical and sensorimotor parameters, tests of emotionality and tests of learning and memory. We report 0% mortality, and statistically significant deficits on all aspects of this battery, including learning and memory deficits up to 2 months post-MCAo. The current study demonstrates that with adequate post-operative care and extensive behavioural testing, assessing the potential of new therapeutants for promoting long-term functional neuroprotection following MCAo in the rat is feasible.