EVIDENCE FOR A PARAVASCULAR FLUID CIRCULATION IN THE MAMMALIAN CENTRAL NERVOUS-SYSTEM, PROVIDED BY THE RAPID DISTRIBUTION OF TRACER PROTEIN THROUGHOUT THE BRAIN FROM THE SUBARACHNOID SPACE
EVIDENCE FOR A PARAVASCULAR FLUID CIRCULATION IN THE MAMMALIAN CENTRAL NERVOUS-SYSTEM, PROVIDED BY THE RAPID DISTRIBUTION OF TRACER PROTEIN THROUGHOUT THE BRAIN FROM THE SUBARACHNOID SPACE
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DOI：
10.1016/0006-8993(85)91383-6
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发表时间：
1985-01-01
期刊：
影响因子：
2.9
通讯作者：
GRADY, PA
中科院分区：
文献类型：
--
作者：
RENNELS, ML;GREGORY, TF;GRADY, PA
在插入脑池插管以引流（CSF）和示踪剂溶液后，将蛋白示踪剂辣根过氧化物酶（HRP）输注到麻醉猫和犬的侧脑室或蛛网膜下腔中。然后在4 min至2 h的输注后间隔后，通过连续脑切片的光学显微镜确定示踪剂的脑内分布。为了定位HRP，将切片与二氨基联苯胺（DAB）或更灵敏的色原四甲基联苯胺（TMB）一起孵育。TMB反应显示示踪剂反应产物在大穿透血管周围的血管周间隙（PVS）内和毛细血管周围的基底层中呈一致的“血管旁”分布，远远超出PVS的终止。HRP输注4分钟后，小动脉周围的示踪剂，但毛细血管和小静脉通常不那么密集划界，6分钟，然而，在整个前脑和脑干的脑实质内微血管系统的概述。在DAB中孵育10或20分钟HRP循环后的切片的EM证实了反应产物的血管旁位置，其也分散在邻近实质的整个细胞外间隙（ECS）中。CSF中的溶质在几分钟内通过与脑实质内血管平行的液体通路进入整个轴突的ECS。通过阻断主动脉或部分结扎头臂动脉来停止或减少脑动脉的搏动，可以防止HRP的快速血管旁流入。CSF和脑ECS之间的溶质交换通常归因于扩散，然而，HRP沿脑实质内微血管沿着进入轴突的速度远远快于在此基础上所能解释的速度。这种明显的对流示踪剂流入可能是通过脑动脉的脉动传输到微血管系统来促进的。据推测，通过CNS的液体循环通过血管旁途径发生。
The protein tracer, horseradish peroxidase (HRP), was infused into the lateral cerebral ventricles or subarachnoid space of anesthetized cats and dogs after insertion of a cisternal cannula to permit drainage of (CSF) and tracer solution. The intracerebral distribution of the tracer was then determined by light microscopy of serial brain sections after postinfusion intervals of 4 min to 2 h. For the localization of HRP, sections were incubated with diaminobenzidine (DAB) or the much more sensitive chromogen, tetramethylbenzidine (TMB). The TMB reaction showed a consistent ''paravascular'' distribution of tracer reaction product, within the perivascular spaces (PVS) around large penetrating vessels and in the basal laminae around capillaries, far beyond the termination of the PVS. After infusion of HRP over 4 min, arterioles were surrounded by the tracer, but capillaries and venules were usually less densely demarcated; by 6 min, however, the intraparenchymal microvasculature was outlined in total throughout the forebrain and brainstem. EM of sections incubated in DAB after 10 or 20 min HRP circulation confirmed the paravascular location of the reaction product, which was also dispersed throughout the extracellular spaces (ECS) of the adjacent parenchyma. Solutes in the CSF have access to the ECS throughout the neuraxis within minutes via fluid pathways paralleling the intraparenchymal vasculature. The rapid paravascular influx of HRP could be prevented by stopping or diminishing the pulsations of the cerebral arteries by aortic occlusion or by partial ligation of the brachiocephalic artery. The exchange of solutes between the CSF and the cerebral ECS has generally been attributed to diffusion, however, HRP enters the neuraxis along the intraparenchymal microvasculature far more rapidly than can be explained on this basis. This apparent convective tracer influx may be facilitated by transmission of the pulsations of the cerebral arteries to the microvasculature. It is postulated that a fluid circulation through the CNS occurs via paravascular pathways.