Abstract
Different housing conditions, including housing space and the physiological and social environment, may affect rodent behavior. Here, we examined the effects of different housing conditions on post-stroke angiogenesis and functional recovery to clarify the ambiguity about environmental enrichment and its components. Male rats in the model groups underwent right middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO rats were divided into four groups: the physical enrichment (PE) group, the social enrichment (SE) group, the combined physical and social enrichment (PSE) group and the ischemia/reperfusion + standard conditioning (IS) group. The rats in the sham surgery (SS) group were housed under standard conditions. In a set of behavioral tests, including the modified Neurological Severity Score (mNSS), rotarod test, and adhesive removal test, we demonstrated that the animals in the enriched condition groups exhibited significantly improved neurological functions compared to those in the standard housing group. Smaller infarction volumes were observed in the animals of the PSE group by MRI detection. The enriched conditions increased the microvessel density (MVD) in the ischemic boundary zone, as revealed by CD31 immunofluorescent staining. The immunochemical and q-PCR results further showed that environmental enrichment increased the expression levels of angiogenic factors after ischemia/reperfusion injury. Our data suggest that all three enrichment conditions promoted enhanced angiogenesis and functional recovery after ischemia/reperfusion injury compared to the standard housing, while only exposure to the combination of both physical and social enrichment yielded optimal benefits.
Highlights
An enriched environment (EE) classically consists of a large amount of space, social enrichment (SE), and diverse multisensory stimulation, which are supposed to facilitate enhanced sensory, cognitive, motor, and social stimulation compared to those provided by standard laboratory housing conditions (Hannan, 2014)
There were no significant differences in modified Neurological Severity Score (mNSS) results among the ischemia/reperfusion groups on day 3 (P > 0.05)
The data suggest that the physical enrichment (PE), SE, and physical and social enrichment (PSE) conditions demonstrated more advantages in promoting functional recovery and angiogenesis than the condition with no enrichment, but only exposure to the PSE condition yielded optimal benefits
Summary
An enriched environment (EE) classically consists of a large amount of space, social enrichment (SE), and diverse multisensory stimulation, which are supposed to facilitate enhanced sensory, cognitive, motor, and social stimulation compared to those provided by standard laboratory housing conditions (Hannan, 2014). EE provides animals with optimal conditions for enhanced exploration, cognitive activity, social interaction, and physical exercise (Wadowska et al, 2015). Johansson and Ohlsson (1996) reported that the effects of physical enrichment (PE) (exercise) in the form of wheel running on motor performance were inferior to those of social interaction. Previous animal studies indicated that social stimulation is an independent factor that promotes beneficial effects on the central nervous system by reducing anxiety-like behaviors, stimulating voluntary exercise, promoting neurogenesis and facilitating functional recovery following stroke (Fowler et al, 2002; Silasi et al, 2008; Cirulli et al, 2010; Xie et al, 2013). Diverse EE paradigms are used between laboratories, with little understanding of how individual EE variables (such as social interactions and physical exercise) might differentially impact specific downstream biological mechanisms
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