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Vascular damage plays an important role in the pathogenesis of radiation-induced brain injury (RBI). Endothelial progenitor cells (EPCs) are responsible for maintaining and repairing endothelial function, and have become a promising method for the treatment of cerebrovascular diseases. However, whether EPC transplantation plays a protective role in RBI has not been fully elucidated. Therefore, the present study investigated the effects of bone marrow-derived EPC transplantation in a whole-brain irradiation (WBI) mouse model. Mice were divided into the three groups: control group, irradiation group and EPCs group. Phosphate buffered saline or EPCs were intravenously injected into mice one week after irradiation, and brains were analyzed eight weeks after injection. Flow cytometry demonstrated that irradiation led to a significant reduction in the peripheral blood EPC count; however, EPC transplantation led to a significant increase in the circulating EPCs. Intravital two-photon imaging and western blotting demonstrated that EPC transplantation reversed the effects of irradiation by decreasing blood-brain barrier permeability and increasing the expression of tight junction proteins in the brain. Additionally, immunofluorescence staining revealed that the brain microvascular density was higher in the EPCs group than the irradiation group. Therefore, EPC transplantation may restore damage caused by WBI to the blood-brain barrier, tight junctions, and cerebral capillary density. These results highlight the potential beneficial effects of EPC transplantation on vascular damage induced by RBI., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Overexpression of vascular endothelial growth factor (VEGF) is considered the most critical factor in radiation-induced brain injury (RBI). To investigate the role of VEGF and the mechanism underlying microvascular damage in RBI, wild type mice, and transgenic mice overexpressing VEGF derived from astrocytes, were separately and randomly exposed to whole-brain or sham irradiation. Pathophysiologic changes in the brain tissue were detected 90 days after irradiation. Compared with wild type mice, the secretion of VEGF and angiopoietin-2 (Ang-2) was up-regulated in transgenic mice, whether irradiated or not, while elevated expression of VEGF, Ang-2, and glial fibrillary acidic protein (GFAP) was detected after whole-brain irradiation using western blotting. Impairment of the blood-brain barrier (BBB) was demonstrated by the leakage of dyes observed using two-photon imaging and decreased expression of zonula occludens-1 (ZO-1) and Occludin. Hematoxylin-eosin (HE) staining revealed obvious structural damage in the irradiated brains. Furthermore, damage to the BBB and histopathology in the transgenic mice were worse than those of wild type mice in the irradiated groups. There was a positive correlation among VEGF and Ang-2 expression and RBI severity. These data reveal that VEGF and Ang-2 expression is closely associated with the microvascular injury in RBI. Further, overexpression of VEGF can cause up-regulation of Ang-2 and exacerbation of RBI. Therefore, Ang-2 might be the cytokine that acts as a mediator between VEGF and microvascular injury, and is likely a new intervention target for RBI., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)