Environmental Enrichment May Alleviate Neural Damage by Reducing Ferroptosis Through Tlr4

Ischemic stroke, particularly cerebral ischemia/reperfusion injury, represents a significant global health challenge, leading to high rates of mortality and disability. This study investigates the neuroprotective effects of environmental enrichment (EE) following middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats, aiming to elucidate underlying molecular mechanisms. Employing a controlled experimental design, we observed that EE significantly reduced neuronal damage and improved functional recovery, as demonstrated through Nissl staining and Longa scale assessments. Gene expression analysis revealed 2003 upregulated and 1056 downregulated genes in the EE group compared to the MCAO group, with significant associations identified in pathways including the PI3K-Akt and MAPK signaling pathways, crucial for cell survival and apoptosis regulation. Additionally, histopathological analysis indicated enhanced neuronal integrity in the EE group. Notably, Tlr4 emerged as a key gene with differential expression, implicating its role in mediating ferroptosis. These findings underscore the potential of EE as a non-invasive therapeutic strategy for neuroprotection in ischemic stroke rehabilitation, highlighting the need for further investigation into its application in clinical settings. Future research should focus on the functional roles of identified differentially expressed genes and the development of targeted interventions that can mimic the beneficial effects of enriched environments.