ESTIMATION OF CAPILLARY-PERMEABILITY OF INULIN, SUCROSE AND MANNITOL IN RAT-BRAIN CORTEX
ESTIMATION OF CAPILLARY-PERMEABILITY OF INULIN, SUCROSE AND MANNITOL IN RAT-BRAIN CORTEX
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DOI：
10.1111/j.1748-1716.1980.tb06678.x
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发表时间：
1980-01-01
期刊：
影响因子：
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通讯作者：
AMTORP, O
中科院分区：
文献类型：
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作者：
AMTORP, O
本研究分析了不同大小亲水性分子14c -菊糖、14c -蔗糖和14c -甘露醇的脑摄取情况。肾结扎后血浆中示踪剂浓度保持恒定。在接近稳态时，测量了大脑皮层中指标的积累。注射5、10、15、30、60 min后，对脑皮层标本进行放射性分析。减去组织中可归因于血液的部分，并估计组织中指标的随时间表观分布体积。胰岛素和蔗糖在脑中的含量没有上升到血浆中的1-2%，甘露醇在脑中的含量没有上升到血浆中的6-7%。对此的解释可能是血液进入大脑的渗透受到限制，以及脑脊液的吸收效应。为了确定指标进入脑脊液的去除，在组织摄取示踪剂期间进行脑室-池灌注；指标在细胞外空间进入灌注的速率可以限制从血液到脑的摄取速率，并对扩散限制的半倍进行了估计。计算表明，组织中指示剂摄取的主要障碍位于脑毛细血管壁；摄取数据允许计算脑毛细血管通透性。指标在其平衡组织分布空间中的分布的半衰期用于估计脑毛细血管通透性。通过与指标水相扩散系数的比较，得出182 ~ 5500道尔顿范围内的物质在通过血脑屏障时受到限制的扩散，存在非歧视性的跨内皮通路。
The present study analyzed the brain uptake of the differently sized hydrophilic molecules 14C-inulin, 14C-sucrose and 14C-mannitol. Constant tracer concentrations were maintained in blood plasma after renal ligation. Accumulation of the indicators was measured in brain cortex during the approach to steady-state. At the conclusion of infusion periods of 5, 10, 15, 30 and 60 min, samples of cerebral cortex were analyzed for radioactivity. Fractions attributable to blood in the tissue were subtracted and time-dependent apparent distribution volumes of the indicators in the tissue were estimated. The brain level did not rise to > 1-2% of that in the plasma for inulin and sucrose and to 6-7% for mannitol. The explanation for this could be a combination of restricted penetration from blood into brain and a sink effect of CSF. To determine the removal of the indicators into csf, ventriculo-cisternal perfusion was performed during the period of tracer uptake in the tissue; the rate of passage of the indicators into perfusion in the extracellular space could limit uptake rates from blood to brain, estimates of diffusion-limited half-times were also made. Calculations showed that the major hindrance to indicator uptake in the tissue is located in the wall of the brain capillaries; the uptake data permit calculation of brain capillary permeability. The half-times for the distribution of the indicators in their equilibrated tissue distribution spaces were used to estimate brain capillary permeability. By comparison with the aqueous diffusion coefficients of the indicators, it is concluded that the substances in the MW range of 182-5500 daltons are subjected to restricted diffusion during the passage of the blood-brain barrier and that non-discriminative transendothelial pathways are available.