Preconditioning with an enriched environment enhances neuroplasticity and functional recovery following cerebral ischemia-reperfusion injury.

Background: This study aimed to examine the effects of preconditioning with an enriched environment (EE) on neuroplasticity following cerebral ischemia-reperfusion (I/R) injury and to elucidate its underlying neuroprotective mechanisms. While prior research has indicated that EE preconditioning may mitigate neuronal apoptosis, the molecular pathways contributing to neuroplasticity enhancement post-I/R injury remain insufficiently characterized.

Methods: Male Sprague-Dawley rats were allocated into three experimental groups: (1) Middle cerebral artery occlusion (MCAO) with pre-ischemic EE exposure (PIEE), (2) pre-ischemic standard condition (SC) exposure with MCAO (PISC), and (3) pre-ischemic SC exposure with sham surgery (Sham). Neurological function and infarct volume were assessed three days post-MCAO. The expression levels of neuroplasticity-related proteins, including neurofilament (NF), synaptophysin (Syn), and microtubule-associated protein 2 (MAP-2), as well as neurotrophic factors such as nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), were analyzed using western blot and immunohistochemical techniques. Correlation analyses were conducted to evaluate the relationship between protein expression and neurological outcomes.

Results: Compared to the PISC group, the PIEE group demonstrated significant improvements in neurological function and reduced infarct volumes. Expression levels of NF, Syn, and MAP-2 were elevated in the ischemic penumbra cortex in the PIEE group. Additionally, EE preconditioning resulted in increased expression of NGF and bFGF. These molecular changes were positively correlated with functional recovery in the MCAO model.

Conclusions: Pre-ischemic exposure to an enriched environment may enhance neuroplasticity and support functional recovery following cerebral I/R injury, potentially through the upregulation of neuroplasticity-associated proteins and neurotrophic factors. These findings support the development of EE-based interventions for ischemic stroke prevention and rehabilitation.