Interstitial fluid flow along white matter tracts: A potentially important mechanism for the dissemination of primary brain tumors
Interstitial fluid flow along white matter tracts: A potentially important mechanism for the dissemination of primary brain tumors
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DOI：
10.1023/a:1005761031077
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发表时间：
1997-05-01
影响因子：
3.9
通讯作者：
Grossman, SA
中科院分区：
文献类型：
--
作者：
Geer, CP;Grossman, SA
高级别星形细胞瘤仍然是不可治愈的，即使这些肿瘤经常出现在现代影像学研究中，很少转移到全身部位，并且可以通过手术和放射治疗进行积极治疗。最近的数据表明，星形细胞瘤细胞沿着白色物质束扩散到大脑的远处区域可能是这些患者生存率低和局部治疗效果有限的原因。星形细胞瘤细胞沿着这些白色物质束的运动可以是主动的或被动的。研究瘤周水肿引起的间质液大量流动导致肿瘤扩散的可能性。将20 μ L氚标记菊粉、Evans蓝和大鼠白蛋白立体定向注射到Sprague-Dawley大鼠的灰白质交界处的右额叶和左颞叶中。6小时后，处死大鼠，取出大脑，冷冻并准备用于定量放射自显影和组织学分析。从放射自显影计算间质流速，并从伊文思蓝，菊粉和组织学数据的运动确定流动途径。在额叶注射的每只动物中，伊文思蓝和菊粉主要局限于同侧大的白色物质束，并从额叶注射部位延伸至枕叶。外囊联合纤维的平均间质液流速为0.86 mm/hr。相比之下，接受颞叶注射的动物的伊文思蓝和菊粉仅限于颞叶。颞叶白色物质束的平均间质液流速为0.61 mm/hr。间质液沿着白色物质束的快速和优先流动以及在额叶和颞叶之间观察到的细胞外液清除的差异可能具有重要的临床意义。这些数据表明，积极治疗瘤周水肿，扩大放射治疗端口，并在治疗计划中考虑肿瘤的位置可能会改善某些患者的治疗结果。对肿瘤扩散机制的进一步了解对于为这种毁灭性恶性肿瘤患者设计更有效的治疗方法至关重要。
High grade astrocytomas remain incurable even though these tumors often appear localized on modern imaging studies, rarely metastasize to systemic sites, and can be aggressively treated with surgery and radiation therapy. Recent data suggest that the dissemination of astrocytoma cells along white matter tracts to distant regions of the brain may be responsible for the poor survival of these patients and the limited impact of local therapies. Movement of astrocytoma cells along these white matter tracts can be active or passive in nature. To study the potential for tumor dissemination by bulk flow of interstitial fluid resulting from peritumoral edema. 20 mu L of tritiated inulin, Evans Blue, and rat albumin were injected stereotactically into the right frontal lobe and the left temporal lobe at the gray-white matter junction in Sprague-Dawley rats. Six hours later, the rats were sacrificed and the brains were removed, frozen and prepared for quantitative autoradiography and histologic analysis. Interstitial flow rates were calculated from the autoradiographs, and flow pathways were determined from the movement of Evans Blue, inulin and histologic data. In each animal injected in the frontal lobe, Evans Blue and inulin were primarily confined to large ipsilateral white matter tracts and extended from the frontal injection site to the occipital lobe. The average interstitial fluid flow rate in the association fibers of the external capsule was 0.86 mm/hr. In contrast, the animals receiving temporal lobe injections had Evans Blue and inulin confined to the temporal lobe. The average interstitial fluid flow rate in the white matter tracts of the temporal lobe was 0.61 mm/hr. The rapid and preferential flow of interstitial fluid along white matter tracts and the differences in the clearance of extracellular fluid observed between the frontal and temporal lobes may have important clinical implications. These data suggest that aggressive treatment of peritumoral edema, expansion of radiotherapy ports, and consideration of the location of the tumor in treatment planning may improve therapeutic outcomes for some patients. An improved understanding of the mechanisms of tumor dissemination is crucial to designing more effective therapeutic approaches for patients with this devastating malignancy.