THE DEVELOPING EXPERIMENTAL APPROACH TO THE IDEA OF A BLOOD-BRAIN-BARRIER - INTRODUCTORY-REMARKS
THE DEVELOPING EXPERIMENTAL APPROACH TO THE IDEA OF A BLOOD-BRAIN-BARRIER - INTRODUCTORY-REMARKS
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DOI：
10.1111/j.1749-6632.1986.tb27146.x
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发表时间：
1986-12-30
影响因子：
5.2
通讯作者：
BRADBURY, MWB
中科院分区：
文献类型：
--
作者：
BRADBURY, MWB
现在的研究者并不总是很清楚，现在的思维有多少是实验和过去思想的产物。只有站在前人的肩膀上，我们才能看得更远。虽然心血管生理学的历史有400多年的历史，但血脑屏障的概念相对较年轻，尽管它已经接近100岁了。这个想法不能明确地归功于一个人，而是由于世纪之交德国对药理学的浓厚兴趣。这个假设基于以下的实验逻辑。某些化合物不能从血液进入大脑，这可以通过缺乏中枢作用或大脑没有染色来判断。同样的化合物，当注射到脑脊液（CSF）中时，可能会引起严重的神经症状，如果是染料，可能会染色邻近的大脑或脊髓。ehrlich3对在血管水平上存在屏障的想法持怀疑态度，并将大脑没有被活体染料染色归因于组织部分缺乏亲和力；然而，他的同事戈德曼对酸性染料台锥蓝的分布进行了仔细而详细的观察，从而回答了这个解释。实验动物全身注射后，大部分组织染色严重，但脑仍为白色，脑脊液无色。将台盼蓝注射到蛛网膜下腔脑脊液中，排除了未染色的脑是由于缺乏亲和力的可能性：在此之后，靠近脑脊液的脊髓和脑组织很容易吸收染料。图1总结了这两种实验的必要解释。血脑和血脑脊液（CSF）屏障最好被认为是独立的实体，因为分离血脑间液和血脑脊液的细胞膜在解剖学上是不同的。在给定的细胞外部位，各细胞膜的相对影响很大程度上取决于解剖条件，但一般来说，脑毛细血管的内皮可能是间质液的主要因素。
It is not always obvious to current investigators how much present thinking is the product of experimentation and ideas of the past. We truly see farther by standing on the shoulders of our predecessors. While the history of cardiovascular physiology covers more than 400 years, the idea of a blood-brain barrier is comparatively young, although approaching its 100th birthday. The idea cannot be unequivocally attributed to one person but was due to the intense interest in pharmacology in Germany at the turn of the century. The hypothesis depended on the following experimental logic. Certain compounds failed to pass from blood into brain as judged by a lack of central action or by a lack of staining of the brain. The same compounds, when injected into cerebrospinal fluid (CSF), might cause dramatic nervous symptoms or, if a dye, stain the adjacent brain or spinal cord.’p2Ehrlich3 was skeptical of the idea of a barrier at the level of the blood vessels and attributed absence of staining of the brain by intravital dyes to a lack of affinity on the part of the tissue; however, his associate Goldmann answered this explanation by his careful and detailed observations on the distribution of the acid dye trypan blue. After systemic injection into experimental animals, most tissues were heavily stained but the brain remained white and the CSF colorless. The possibility that the unstained brain was due to lack of affinity was excluded by injection of trypan blue into the subarachnoid cerebrospinal fluid: After this, spinal cord and brain tissue, adjacent to the CSF, took up the dye readily. The necessary interpretation of the two types of experiment is summarized in FIGURE 1. The blood-brain and blood-cerebrospinal fluid (CSF) barriers are best considered to be separate entities, since the cellular membranes separating blood-cerebral interstial fluid on one hand and blood-CSF on the other are anatomically different. At a given extracellular site, the relative influence of each cellular membrane must largely depend on the anatomical conditions but in general the endothelium of cerebral capillaries is likely to be the dominant factor for interstitial fluid.