Cognitive rehabilitation reduces cognitive impairment and normalizes hippocampal CA1 architecture in a rat model of vascular dementia

摘要

Dementia is a major cause of morbidity in the western society. Pharmacological therapies to delay the progression of cognitive impairments are modestly successful. Consequently, new therapies are urgently required to improve cognitive deficits associated with dementia. We evaluated the effects of physical and cognitive activity on learning and memory in a rat model of vascular dementia (VasD). Male Sprague-Dawley rats (6 months old) were exposed to either regular chow or a diet rich in saturated fats and sucrose and chronic bilateral common carotid artery occlusion or sham surgery. First, this model of VasD was validated using a 2 × 2 experimental design (surgery × diet) and standard cognitive outcomes. Next, using identical surgical procedures, we exposed animals to a paradigm of cognitive rehabilitation or a sedentary condition. At 16 weeks post surgery, VasD animals demonstrated significant learning and memory deficits in the Morris water maze, independent of diet. Rehabilitation significantly attenuated these cognitive deficits at this time point as well as at 24 weeks. Further, rehabilitation normalized hippocampal CA1 soma size (area and volume) to that of control animals, independent of cell number. Importantly, these findings demonstrate beneficial neuroplasticity in early middle-aged rats that promoted cognitive recovery, an area rarely explored in preclinical studies.