Objectives

After cerebral ischaemia the blood–brain barrier (BBB) may be compromised and this has been observed in both clinical and preclinical studies. The timing of BBB disruption after ischaemia has long been considered to be biphasic, however some groups contest this view. Therefore, the purpose of this study was to characterize the BBB permeability timecourse in a rat model at both acute and chronic time points

Methods

Unilateral transient middle cerebral artery occlusion (tMCAO) was performed in 15 male Sprague Dawley rats. Change in T1-weighted MR signal before and after an injection of gadolinium-based contrast agent was calculated voxelwise to derive a BBB permeability index (BBBPI) at both early (6 h, 12 h, and 24 h) and late (7 and 14 days) time points.

Results

As expected, BBBPI in the non-lesioned ROI was not significantly different from pre-occlusion baseline at any time point. However, BBBPI in the ipsilateral (lesioned) ROI was statistically different to baseline at day 7 (p < 0.001) and day 14 (p < 0.01) post-tMCAO. There was a small, but not-significant increase in BBBPI in the earlier phase (at 6 hours).

Discussion

Our results indicate a significant late opening of the BBB. This is important as the majority of previous studies have only characterised an early acute BBB permeability in ischemia. However, the later period of increased permeability may indicate an optimal time for drug delivery across the BBB, when it is especially suited to drugs targeting delayed processes.

中文翻译：

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t增强MRI在大鼠tMCAO中风模型中血脑屏障通透性的晚期变化。

目标

脑缺血后，血脑屏障（BBB）可能受损，这在临床和临床前研究中均已观察到。长期以来，缺血后血脑屏障破裂的时间被认为是两相的，但是一些团体对此观点提出了质疑。因此，本研究的目的是表征大鼠模型在急性和慢性时间点的血脑屏障通透性时程

方法

在15只雄性Sprague Dawley大鼠中进行了单侧短暂性大脑中动脉闭塞（tMCAO）。垂直计算an基造影剂注射前后T1加权MR信号的变化，以得出早期（6 h，12 h和24 h）和晚期（7和14）的BBB通透性指数（BBBPI）天）的时间点。

结果

不出所料，在任何时间点，非病变ROI中的BBBPI与阻塞前基线均无显着差异。但是，tMCAO后第7天（p <0.001）和第14天（p <0.01），同侧（病变）ROI中的BBBPI在统计学上与基线不同。在早期阶段（6小时时），BBBPI有所增加，但不显着。

讨论区

我们的结果表明BBB的开盘时间很晚。这很重要，因为以前的大多数研究仅以局部缺血早期急性BBB通透性为特征。但是，当通透性增加的后期特别适合靶向延迟过程的药物时，通透性增加的后期可能表明药物通过BBB的最佳时间。