Molecular mechanisms of radiation‐induced brain injury

Abstract

The present study was designed to address potential cellular and molecular mechanisms that contribute to brain injury after irradiation. Primary rat astrocytes and rat brain microvascular endothelial cells (RBE4), which are major components of the blood-brain barrier (BBB), were exposed to a single dose of 5 Gy and incubated for up to 48 h following irradiation. To investigate the pro-inflammatory mechanisms of brain injury by irradiation, expression of a variety of pro-inflammatory mediators was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). A marked increase in expression of interleukin-6 (IL-6) and matrix metalloproteinases (MMP-2 and MMP-9) was observed in astrocytes after irradiation. Irradiation also up-regulated expression of tumor necrosis factor-α (TNF-α) and IL-6 in RBE4 cells. In addition, expression levels of vascular endothelial growth factor (VEGF) were determined in astrocytes and RBE4 cells to examine the effects of radiation on angiogenic factors. Exposure of both astrocytes and brain endothelial cells to radiation significantly down-regulated VEGF expression. These data suggest that radiation-induced brain injury may be mediated through two independent mechanisms: the pro-inflammatory pathways by up-regulation of inflammatory mediators and the cerebrovascular rarefaction by down-regulation of VEGF. (This work was supported by CA112593 and VMRCVM New Initiative Grants)