Low-dose Ionizing Radiation, a Protective Intervention to Mitigate Chronic Cerebral Hypoperfusion-induced Brain Damage and Cognitive Deficits in the Rat

Vascular dementia is a leading cause of cognitive decline, with few effective treatment options currently available. Within the framework of hormesis, treatment with low-dose ionizing radiation (LDIR<0.1 Gy) has been proposed as a promising therapy for neurodegenerative diseases. This study investigates the effects of LDIR on cognitive decline, brain damage, blood-brain barrier permeability, and oxidative stress in a rat model of vascular dementia. After chronic cerebral hypoperfusion (CCH), the whole brain was exposed to 0.3 Gy of X rays, delivered in 0.1 Gy fractions over three consecutive days, beginning at day 1 or day 7 after occlusion. LDIR effects were evaluated using behavioral tests, MRI, post-mortem analyses, and in vitro analyses. Early exposure to LDIR attenuated recognition memory deficits induced by CCH. LDIR applied one day after occlusion reduced alterations in brain tissue integrity attributed to CCH and mitigated neuronal loss in the hippocampus. Moreover, LDIR counteracted CCH-induced blood-brain barrier permeabilization and improved survival of epithelial cells subjected to oxygen-glucose deprivation/reoxygenation. LDIR modulated oxidative stress by altering the reactive species interactome and activating antioxidant enzymes. Brain exposure to low-dose ionizing radiation modulates the events triggered by CCH and thus attenuates cognitive decline and brain damage in the rat.