Erythropoietin Ameliorates Lead‑Induced Cognitive Impairment Through Attenuation of Hippocampal Neurodegeneration in Male Wistar Rats

Abstract

Introduction: Lead, as a potent neurotoxin, induces neurodegeneration and cell death, leading to significant structural damage of the hippocampus and impairments in hippocampal dependent learning and memory. Erythropoietin (EPO), a glycoprotein hormone with a strong potential to enhance neuronal survival, has emerged as a promising candidate for mitigating various forms of neurotoxic injury. This study aimed to evaluate the neuroprotective effects of EPO against lead induced hippocampal damage in male Wistar rats.

Methods: Animals were randomly allocated into four groups: control, lead, lead + EPO (1000 IU/kg), and lead + EPO (2500 IU/kg). Lead acetate (25 mg/kg) was administered intraperitoneally for three consecutive days, followed by EPO for seven days. Cognitive performance was assessed using the Novel Object Recognition test, and neurodegeneration was evaluated by hematoxylin–eosin staining.

Results: Lead exposure significantly impaired recognition memory and increased hippocampal neurodegeneration indices (P<0.001). Administration of EPO at both 1000 IU kg and 2500 IU kg significantly improved the discrimination index (P<0.001, P<0.05), reduced pyknotic neurons (P<0.001, P<0.05), decreased vacuolization (P<0.01, P<0.05), and increased the percentage of morphologically intact neurons (P<0.001, P<0.01) relative to the lead group.

Conclusion: These findings suggest that EPO confers significant protective effects, including improvement of cognitive performance, against lead induced neurotoxicity through attenuation of hippocampal neurodegeneration.