Not only angiogenesis but also inflammation participate in the pathophysiology of brain radiation necrosis

通过苏木精-伊红(H&E)染色和免疫组织化学染色，对脑部有症状的肾小球肾炎手术标本进行了回顾性分析，发现最显著的血管生成是薄壁渗漏血管生成，即毛细血管扩张，周围有明显的间质水肿。有两种主要细胞表型：GFAP阳性反应性星形胶质细胞和CD68/hGLUT-5阳性细胞(主要是小胶质细胞)。血管内皮细胞生长因子可导致RN血管渗漏和皮损周围水肿。表达CXCL12的GFAP阳性细胞可能将表达CXCR4的CD68/hGLUT5阳性细胞吸引到坏死周围。这些聚集的表达促炎细胞因子的CD68/hGLUT5阳性细胞似乎加重了RN的水肿。血管生成和炎症可能都是由HIF-1a的调节引起的，HIF-1a是众所周知的血管内皮生长因子和CXCL12/CXCR4趋化素轴的反式激活因子。

Surgical specimens of symptomatic RN in the brain were retrospectively reviewed by histological and immunohistochemical analyses using hematoxylin and eosin (H&E) staining as well as immunohistochemical staining.The most prominent vasculature was identified as thin-walled leaky angiogenesis, i.e., telangiectasis surrounded by prominent interstitial edema.Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive reactive astrocytes and CD68/hGLUT-5-positive cells (mainly microglias). VEGF caused leaky angiogenesis followed by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines seemed to aggravate the RN edema. Both angiogenesis and inflammation might be caused by the regulation of HIF-1a, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.