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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >JOURNAL OF NEUROCHEMISTRY
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JOURNAL OF NEUROCHEMISTRY

机译：神经化学杂志

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The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1M PAF for 1h significantly increased monolayer permeability to I-125-albumin, which recovered 1h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain.
机译：血脑屏障（BBB）极大地限制了许多神经保护药物向大脑的递送功效，因此提高药物通过BBB的渗透一直是研究的重要重点。在这里我们报告血小板活化因子（PAF）暂时打开血脑屏障，并促进神经保护剂依达拉奉渗透入大脑。 PAF静脉输注可导致大鼠短暂的血脑屏障开放，这反映为伊文思蓝漏液增加和轻度浮肿形成，该现象在6小时内停止。此外，在PAF输注期间，大鼠局部脑血流量（rCBF）急剧下降，但恢复缓慢。更重要的是，这种短暂的BBB开口显着增加了依达拉奉对大脑的渗透，这可以通过微透析收集的组织间液中依达拉奉浓度的增加来证明，并通过超高效液相色谱仪和混合四极杆飞行时间质谱仪进行分析（ UPLC-MS / MS）。同样，将大鼠脑微血管内皮细胞单层与1M PAF孵育1h会显着提高单层对I-125-白蛋白的渗透性，PAF消除后1h即可恢复。但是，PAF与大鼠脑微血管内皮细胞一起温育1h不会引起可检测的细胞毒性，并且不能调节细胞间粘附分子1，基质金属蛋白酶9和P糖蛋白的表达。总之，PAF可能通过突然的rCBF下降诱导短暂和可逆的BBB开放，从而显着改善了依达拉奉向大脑的渗透。

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