Rennels M L, Gregory T F, Blaumanis O R, Fujimoto K, Grady P A
Brain Res. 1985 Feb 4;326(1):47-63. doi: 10.1016/0006-8993(85)91383-6.
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 cerebrospinal fluid (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-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 toto throughout the forebrain and brainstem. Electron microscopy 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. Our results demonstrate that 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. We postulate that a fluid circulation through the CNS occurs via paravascular pathways.
在插入枕大池插管以引流脑脊液（CSF）和示踪剂溶液后，将蛋白质示踪剂辣根过氧化物酶（HRP）注入麻醉猫和狗的侧脑室或蛛网膜下腔。在注入示踪剂4分钟至2小时的不同时间间隔后，通过对连续脑切片进行光学显微镜检查来确定示踪剂在脑内的分布。为了定位HRP，切片用二氨基联苯胺（DAB）或更灵敏的显色剂四甲基联苯胺（TMB）孵育。TMB反应显示示踪剂反应产物呈一致的“血管旁”分布，位于大的穿通血管周围的血管周围间隙（PVS）内以及毛细血管周围的基膜中，远远超出了PVS的终止部位。在4分钟内注入HRP后，小动脉被示踪剂包围，但毛细血管和小静脉通常标记不太密集；然而，到6分钟时，整个前脑和脑干的脑实质内微血管系统已全部勾勒出来。在HRP循环10或20分钟后，对用DAB孵育的切片进行电子显微镜检查，证实反应产物位于血管旁，并且也分散在相邻脑实质的细胞外间隙（ECS）中。我们的结果表明，CSF中的溶质可在数分钟内通过与脑实质内血管系统平行的液体途径进入整个神经轴的ECS。通过主动脉阻断或部分结扎头臂动脉来停止或减少脑动脉的搏动，可以阻止HRP快速的血管旁流入。CSF与脑ECS之间溶质的交换通常归因于扩散，然而，HRP沿脑实质内微血管系统进入神经轴的速度比基于此所能解释的要快得多。这种明显的对流示踪剂流入可能是由于脑动脉的搏动传递到微血管系统而促进的。我们推测，一种通过血管旁途径的液体循环在中枢神经系统中发生。
