Abstract Body: Epidemiological studies carried out on cohorts of nuclear workers suggest a relationship between exposure to low and moderate doses of ionizing radiation (IR) and the risk of cerebrovascular diseases and dementia. To date, experimental studies on the risk of vascular disease in the low-dose range have mainly focused on inflammatory diseases of large vessels such as atherosclerosis and have shown no deleterious effect. Microvascular alterations, however, which are strongly associated with cerebrovascular pathologies and their morbidity, have mainly been studied only at high dose ranges. Furthermore, established risk factors such as obesity increase the incidence of microvascular diseases.
We assessed the hypothesis that co-exposure to a lipid-rich diet and acute low-to-moderate doses of IR leads to endothelial dysfunction in the cerebral microcirculation.
Male C57BL/6J mice fed either a high-fat diet or a normal diet, were acutely exposed to total-body irradiation from an external gamma radiation source doses of 300 mGy and 1 Gy. Sacrifice and analysis were conducted at different time-points after irradiation. Microvascular density in the hippocampus was assessed by immunostaining for vascular markers in brain slices. The expression of genes related to oxidative stress, inflammation, endothelial dysfunction and vascular remodeling was evaluated by RT-PCR.
Six months after co-exposure to 1 Gy and a high-fat diet, we observed an increase in vascular density at both 3- and 6-months post-irradiation, without changes in the expression of angiogenic parameters at earlier time points. We also observed an upregulation in the expression of genes encoding chemokines and vascular adhesion molecules, suggesting long-term endothelial dysfunction and inflammation.
In conclusion, this study demonstrates a potentiating effect of obesity as an additional risk factor that enhances the impact of moderate doses of ionizing radiation on brain microcirculation. These results are of significant medical and industrial interest in the context of low and moderate-dose exposure to IR.