Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis.
Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis.
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DOI：
10.1093/jrr/rru017
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发表时间：
2014-07
影响因子：
2
通讯作者：
Miyatake S
中科院分区：
文献类型：
--
作者：
Yoritsune E;Furuse M;Kuwabara H;Miyata T;Nonoguchi N;Kawabata S;Hayasaki H;Kuroiwa T;Ono K;Shibayama Y;Miyatake S
强化放射治疗后的放射性坏死（RN）是一个严重的问题。最近，我们使用人RN标本证明了血管渗漏是RN脑水肿的主要原因。在本研究中，我们研究了相同的标本，推测炎症对RN的病理生理学的影响。采用苏木精-伊红（H&E）染色及免疫组化染色对手术切除的RN标本进行组织学和免疫组化分析，并对VEGF、HIF-1α、CXCL 12、CXCR 4、GFAP、CD 68、hGLUT 5、CD 45、IL-1α、IL-6、TNF-α和NF-κ B进行免疫组化染色。H&E染色显示坏死区有明显的血管生成和细胞浸润。最显著的血管系统被确定为薄壁渗漏性血管生成，即毛细血管扩张被显著的间质水肿包围。两种主要的细胞表型浸润周围坏死区：GFAP阳性反应性星形胶质细胞和CD 68/hGLUT 5阳性细胞（主要是小胶质细胞）。免疫组化显示CD 68/hGLUT 5阳性细胞表达HIF-1α，GFAP阳性细胞表达VEGF。GFAP阳性细胞表达趋化因子CXCL 12，CD 68/hGLUT 5阳性细胞表达受体CXCR 4。CD 68/hGLUT 5阳性细胞在坏死区表达促炎细胞因子IL-1α、IL-6和TNF-α。血管内皮生长因子导致RN血管生成渗漏，随后出现病灶周围水肿。表达CXCL 12的GFAP阳性细胞可能吸引表达CXCR 4的CD 68/hGLUT 5阳性细胞进入坏死周围区。这些积累的表达促炎细胞因子的CD 68/hGLUT 5阳性细胞似乎加重了RN水肿。血管生成和炎症可能都是由HIF-1α的调节引起的，HIF-1 α是众所周知的VEGF和CXCL 12/CXCR 4趋化因子轴的反式激活因子。
Radiation necrosis (RN) after intensive radiation therapy is a serious problem. Using human RN specimens, we recently proved that leaky angiogenesis is a major cause of brain edema in RN. In the present study, we investigated the same specimens to speculate on inflammation's effect on the pathophysiology of RN. 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 for VEGF, HIF-1α, CXCL12, CXCR4, GFAP, CD68, hGLUT5, CD45, IL-1α, IL-6 TNF-α and NF-kB. H&E staining demonstrated marked angiogenesis and cell infiltration in the perinecrotic area. 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/hGLUT5-positive cells (mainly microglias). Immunohistochemistry revealed that CD68/hGLUT5-positive cells and GFAP-positive cells expressed HIF-1α and VEGF, respectively. GFAP-positive cells expressed chemokine CXCL12, and CD68/hGLUT5-positive cells expressed receptor CXCR4. The CD68/hGLUT5-positive cells expressed pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in the perinecrotic area. 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-1α, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.
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DOI：
10.1016/j.ijrobp.2009.12.061
发表时间：
2011-04-01
影响因子：
7
作者：
Levin, Victor A.;Bidaut, Luc;Hou, Ping;Kumar, Ashok J.;Wefel, Jeffrey S.;Bekele, B. Nebiyou;Prabhu, Sujit;Loghin, Monica;Gilbert, Mark R.;Jackson, Edward F.
通讯作者：
Jackson, Edward F.
DOI：
10.1084/jem.20102010
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cruz-Orengo L;Holman DW;Dorsey D;Zhou L;Zhang P;Wright M;McCandless EE;Patel JR;Luker GD;Littman DR;Russell JH;Klein RS
通讯作者：
Klein RS
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
4.1
作者：
Miyatake, SI;Kawabata, S;Ono, K
通讯作者：
Ono, K
影响因子：
15.9
作者：
Miyatake, Shin-Ichi;Kawabata, Shinji;Ono, Koji
通讯作者：
Ono, Koji