Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF
Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF
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DOI：
10.1016/0169-328x(95)00250-v
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发表时间：
1996-03-01
期刊：
影响因子：
--
通讯作者：
Curran, GL
中科院分区：
文献类型：
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作者：
Poduslo, JF;Curran, GL
用渗透系数-表面积（PS）乘积法比较了不同神经营养因子在正常成年大鼠血脑屏障（BBB）和血神经屏障（BNB）上的渗透性。在插管的肱静脉和动脉中使用静脉推注技术，使用第二种碘同位素（I-125 vs. I-131）放射性碘标记的相同蛋白质分别测定PS和V-p值。血浆洗脱显示血浆半衰期按脑源性神经营养因子（BDNF）<神经营养因子-3（NT-3）<睫状神经营养因子（CNTF）<神经生长因子（NGF）的顺序降低。BNB处NGF的PS为1.40 +/-0.15 X 10（-6）ml/g/s（（x）条+/- SEM）。其他神经营养蛋白均显著高于NGF（CNTF：9.5 X; NT-3：20.8 X; BDNF：18.9 X）。在BNB处，NGF的V-p为1.92 +/- 0.12 μ l/g，并且与除NGF与BDNF之外的其它蛋白质没有显著差异（P < 0.05）。6个不同脑区的血脑屏障中NGF的PS范围为1.5 - 2.7 × 10 ~（-6）ml/g/s。CNTF的PS比NGF高6.0至8.0倍; NT-3高10.6至15.2倍; BDNF高11.3至16.4倍。除海马和皮层CNTF外，其余各组V-p值差异无显著性（P> 0.05）。所有放射性碘标记的神经营养蛋白的SDS-PAGE分析后60分钟的摄取显示完整的蛋白质在神经内膜和在6个不同的大脑区域与曝光时间为2-42天。这些神经营养蛋白的渗透性的定量提供了基线值，用于比较增强PS同时仍保留神经营养活性的不同蛋白质修饰（例如，蛋白质糖化; Poduslo和Curran，Mol. Brain Res.，23（1994）157）。修饰后渗透性增强可能允许使用这些蛋白质的全身递送用于各种神经退行性疾病的实际治疗性治疗。
A comparison was made of the permeabilities of different neurotrophic factors at the blood-brain barrier (BBB) and blood-nerve barrier (BNB) in normal adult rats by quantifying the permeability coefficient-surface area (PS) product after correction for the residual plasma volume (V-p) occupied by the protein in the capillary bed of the nerve endoneurium or different brain regions. The i.v. bolus injection technique was used in the cannulated brachial vein and artery using the same protein radioiodinated with a second isotope of iodine (I-125 vs. I-131) to separately determine the PS and V-p values. The plasma washout showed a decreasing plasma half-life in the order of brain-derived neurotrophic factor (BDNF) < neurotrophin-3 (NT-3) < ciliary neurotrophic factor (CNTF)< nerve growth factor (NGF). The PS at the BNB for NGF was 1.40 +/- 0.15 X 10(-6) ml/g/s ((x) over bar +/- SEM). The other neurotrophic proteins were all significantly higher than NGF (CNTF: 9.5 X; NT-3: 20.8 X; BDNF: 18.9 X). The V-p for NGF at the BNB was 1.92 +/- 0.12 mu l/g and was not significantly different from the other proteins except for NGF vs. BDNF (P < 0.05). The PS for NGF at the BBB ranged from 1.5 to 2.7 X 10(-6) ml/g/s for six different brain regions. The PS for CNTF ranged from 6.0 to 8.0-fold higher than NGF; NT-3: 10.6 to 15.2-fold higher; and BDNF: 11.3 to 16.4-fold higher. The V-p values were not significantly different except for CNTF in the hippocampus and cortex (P < 0.05). SDS-PAGE analyses of all the radioiodinated neurotrophic proteins after 60 min of uptake revealed intact protein in the endoneurium and in the six different brain regions with exposure times of 2-42 days. The quantification of the permeability of these neurotrophic proteins provides baseline values for comparison of different protein modifications that enhance the PS while still preserving the neurotrophic activity (e.g., protein glycation; Poduslo and Curran, Mol. Brain Res., 23 (1994) 157). Enhanced permeability following modification might allow the use of systemic delivery of these proteins for practical therapeutic treatment of various neurodegenerative disorders.