Oleuropein Mitigates Radiation‐Induced Neurodegeneration in Rats by Modulating Oxidative, Vascular, and Apoptotic Pathways

Radiation (RAD) is widely used in medicine but poses risks to non‐regenerative tissues such as the brain. This study aimed to investigate the neuroprotective effects of oleuropein (OLE) against RAD‐induced brain injury in rats by evaluating oxidative stress, apoptosis, and vascular responses. Thirty‐two male Wistar rats were randomly assigned to four groups: Control, RAD (6 Gy cranial irradiation), RAD+OLE (50 mg/kg/day oral gavage, initiated 1 week before and continued 3 weeks after irradiation), and OLE alone. Histopathological (H&E, PAS), immunohistochemical (Cyclin‐D1, CD31, GLUT‐1), biochemical (serum CK‐BB), and molecular (Bax, Bcl‐2 mRNA via RT‐qPCR) analyses were performed. RAD exposure resulted in significant neuronal degeneration, upregulation of Cyclin‐D1, CD31, and GLUT‐1 expression, increased pro‐apoptotic Bax, decreased anti‐apoptotic Bcl‐2, and elevated serum CK‐BB ( p < 0.05). OLE treatment significantly attenuated these alterations, restoring brain tissue architecture, normalizing PAS staining, downregulating apoptotic and vascular markers, and reducing CK‐BB levels ( p < 0.05). These findings suggest that OLE exerts potent neuroprotective effects against RAD‐induced brain damage by attenuating oxidative stress, vascular activation, and apoptosis. OLE may serve as a promising adjuvant in radiotherapy to reduce central nervous system (CNS) side effects. Further studies focusing on functional outcomes and dose optimization are warranted.