Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase.

External stimuli, including environmental enrichment (EE) and physical activity, have been shown to significantly facilitate recovery from brain injury. However, whether EE can be used as a preconditioning method to induce cerebral ischemic tolerance has never been investigated. Furthermore, whether, and to what extent, such environmental stimuli regulate physical activity to promote neuroprotection is largely unclear. To examine the neuroprotective effects of pre-ischemic EE (PIEE) and to investigate the relationship between these effects and EE-induced physical activity, we tested neurobehavioral and morphological recovery of rats following transient focal cerebral ischemia. Our study showed that PIEE improved the recovery of motor function, spatial learning and memory without reduction in brain edema or infarct volume. We also found that PIEE robustly increased the level of physical activity of rats that positively correlated with the extent of neurobehavioral recovery. Our results suggest that PIEE may induce brain ischemic tolerance through, at least partially, increasing physical activity. Crown