RESUMO
Objective: This study delves into the impact of erythropoietin (EPO) on hippocampal neurons and its potential implications for sports performance, fitness, and the cognitive well-being of football players facing vascular cognitive impairment. Methodology: The study employs a comprehensive approach, utilizing a rat model of vascular dementia (VaD) induced by bilateral carotid artery ligation. Exogenous EPO is administered to the VaD rat model. Observations of EPO's influence on hippocampal neurons are made, and in vitro experiments are conducted to validate the specific mechanisms at play, particularly under oxygen/glucose-deprived conditions. Results: The results reveal several noteworthy findings. VaD rats treated with EPO demonstrate significantly shorter escape latency, increased neuronal populations, and enhanced preservation of Nissl bodies in hippocampal subfields, specifically cortical area 1 (CA1) and CA2. Moreover, these rats exhibit a lower count of TUNEL-positive cells compared to the model group, with higher doses of EPO demonstrating more notable improvements in escape latency. Molecular analysis shows that EPO up-regulates key protein expressions, including phosphorylated EPO receptor (p-EPOR), p-phosphatidylinositol 3-kinase (p-PI3K), p-protein kinase B (Akt), and p-cyclic AMP response element binding protein (p-CREB). Simultaneously, it down-regulates expressions of apoptosis- and autophagy-related proteins, such as B-cell lymphoma-2-associated X protein (Bax), cleaved-Caspase 3, cleaved-Caspase 9, light chain 3β (LC3β), Beclin, autophagy-related gene 5 (ATG5), and ATG7. Notably, in vitro experiments confirm the role of the PI3K/AKT pathway in EPO's mechanisms, with implications for cognitive health. (AU)