P2X7 Receptor mediates the activation and paracrine of microglia in radiation-induced brain injury

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Yamei Tang, Bin Hu, Jue Wang, Rui Pan, Xiaolei Shi and Wangqing Cai

Accepted Abstracts: J Cancer Sci Ther

Abstract :

Previous studies found that extracellular ATP could cause apoptosis via P2X7 receptor. We have known that activation of microglia plays an important role in the development of radiation-induced brain injury. P2X7 receptor, as a specific ionselective purinergic receptor, was reported to participate in the paracrine and activation of microglia. However, it remains unclear whether ATP and P2X7 are involved in the pathophysiological alteration of radiation induced brain injury. In our study, we found that the patients? clinical severity of radiation-induced brain injury was correlated with the ATP concentration in their CSF. Also, higher ATP level indicated a larger edema and necrosis volume in MRI as well as higher LENT/SOMA scores, which suggested that ATP may be a possible indicator for radiation induced brain injury. In addition, we tested the inflammatory cytokines in the patients? CSF and we found that ATP was positive correlated with cytokines including Cox-2, TNF-a and IL-6. Furthermore, BV-2 cells and C57/BL6J mice were used to establish radiation-induced brain injury model. Microglia was activated after radiation and turned into an amoeba-like shape with bigger soma and thicker elongation of protrusion. The mRNA expressions and the protein expressions of P2X7, Cox-2, IL-6 and TNF-α significantly increased after radiation, via the PI3K/AKT and NF-κB signal pathway. After the P2X7 RNA interference or brilliant blue G(BBG, a specific P2X7 inhibitor) treatment, the mRNA expressions of P2X7, IL-6 and Cox-2 and the protein expressions of P2X7 and Cox-2 significantly decreased (P<0.05). Moreover, BBG promoted the proliferation of Brdu+ cells in the hippocampus of C57/BL6J mice. Our study demonstrated that P2X7 receptor plays a key role in the process of microglia activation after radiation.