Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.
Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.
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DOI：
10.1007/s11060-012-1006-1
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发表时间：
2013-01
影响因子：
3.9
通讯作者：
Miller, Donald W.
中科院分区：
文献类型：
--
作者：
On, Ngoc H.;Mitchell, Ryan;Savant, Sanjot D.;Bachmeier, Corbin. J.;Hatch, Grant M.;Miller, Donald W.
关键词：
本研究从功能和生化两个方面评价了脑肿瘤引起的脑毛细血管内皮细胞的改变。采用立体定向仪，将Lewis肺癌(3LL)细胞注入Balb/c小鼠右侧大脑半球，诱发小鼠脑肿瘤。在肿瘤发展的不同阶段，使用放射性标记示踪剂渗透性和磁共振成像(MRI)和二乙三胺-五醋酸钆对比增强(Gad-DTPA)来评估血脑屏障(BBB)的通透性。用Western印迹和免疫组织化学方法检测药物外排转运体P-糖蛋白(P-gp)在肿瘤不同发展阶段血脑屏障中的表达。注射肿瘤细胞后小鼠的中位生存期为17天。注射后第7天和第10天，双侧大脑半球血脑屏障对~3H-甘露醇的通透性相似。至第15天，肿瘤带瘤半球的~3H-甘露醇渗透率是非肿瘤半球的2倍。Gad-DTPA增强MRI检查血脑屏障通透性显示脑血管通透性改变局限于肿瘤区域。在肿瘤发展的后期观察到的通透性增加与脑血管体积的增加相关，这表明肿瘤大脑半球内有血管生成。此外，在肿瘤区域内观察到的Gad-DPTA增强明显低于在未受血脑屏障保护的脑室周围器官内观察到的Gad-DPTA增强。在研究的所有时间点，P-gp在脑的肿瘤和非肿瘤部位的表达似乎是相似的。这些研究表明，尽管在肿瘤发育的后期，血脑屏障的完整性会发生改变，但血脑屏障仍然具有功能，在肿瘤内和肿瘤周围的溶质和药物渗透性方面是有限的。
The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor.
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影响因子：
3.9
作者：
Hall, Walter A.;Doolittle, Nancy D.;Neuwelt, Edward A.
通讯作者：
Neuwelt, Edward A.
影响因子：
3
作者：
GOLDSTEIN, GW;BETZ, AL
通讯作者：
BETZ, AL
DOI：
10.1097/01.rmr.0000245464.36148.dc
发表时间：
2006-04-01
期刊：
Topics in magnetic resonance imaging : TMRI
影响因子：
--
作者：
Essig, Marco;Weber, Marc-Andre;Giesel, Frederik L
通讯作者：
Giesel, Frederik L
影响因子：
15.9
作者：
Fellner, S;Bauer, B;Fricker, G
通讯作者：
Fricker, G
影响因子：
2.4
作者：
Sato, S;Kawase, T;Suga, S
通讯作者：
Suga, S