Predictable ventricular shift after focal cerebral ischaemia in rats: practical considerations for intraventricular therapeutic interventions

Predictable ventricular shift after focal cerebral ischaemia in rats: practical considerations for intraventricular therapeutic interventions
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DOI:
10.1258/la.2009.009043
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发表时间:
2010-04-01
期刊:
影响因子:
2.4
通讯作者:
Simeonidou, C.
Simeonidou, C.
中科院分区:
医学4区
文献类型:
--
作者:
Lourbopoulos, A.;Grigoriadis, N.;Simeonidou, C.

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脑室内给药途径是研究局灶性缺血后脑室内化学物质或细胞移植物作用的有效实验方法。然而,诱导的水肿可能导致结构脱位现象,使立体定向ICV侵袭变得困难,实际上无法实现,特别是在急性缺血后阶段。本研究的目的是测量这些结构性心室脱位,并为局灶性脑缺血后6-18小时成功和经济有效的ICV侵袭设定新的立体定位坐标。Wistar大鼠大脑中动脉闭塞2 h,进行神经学评估(改良神经卒中量表[mNSS]、改良Bederson量表[mBS]和网格行走试验[GWT]),并在闭塞后6和18 h研究脑切片,观察梗死体积、半球水肿、中线脱位和侧脑室立体定向。我们的数据表明,在两个时间点,梗死半球和对侧半球侧脑室的立体定位坐标发生了显著变化(P < 0.05),并与mNSS、mBS和一些GWT评分呈线性相关(P < 0.001)。这种相关性允许计算简单的(线性)数学方程(立体坐标= b0 + b1 * mNSS,其中‘b0’和‘b1’分别是通过回归分析计算的固定数字和因子),从而确定每种动物的单独新坐标。验证实验显示,新坐标使ICV侵袭在多达80%的梗死大鼠(治疗所需的数量为1.65)中可行,而在正常大鼠中使用经典坐标仅为19.4%。因此,我们提出了一种新的、时间和成本效益的方法,用于t-MCAO后6-18小时的大鼠实际可行的ICV入侵。
Intracerebroventricular (ICV) route of administration is a useful experimental method to study the effects of chemicals or cellular grafts in the ventricular compartment of the brain after focal ischaemia. However, the induced oedema may cause structural dislocating phenomena and render a stereotaxic ICV invasion difficult and practically unavailable especially during the acute post-ischaemia phase. The aim of this study was to measure these structural ventricular dislocations and set new stereotaxic coordinates for successful and cost-effective ICV invasion 6-18 h after focal cerebral ischaemia. Wistar rats were subjected to 2 h middle cerebral artery occlussion (t-MCAO), were neurologically evaluated (modified Neurological Stroke Scale [mNSS], modified Bederson's Scale [mBS] and grid-walking test [GWT]) and brain slides were studied at 6 and 18 h post-occlusion for infarction volume, hemispheric oedema, middle line dislocation and stereotaxia of the lateral ventricles. Our data indicated that stereotaxic coordinates of the lateral ventricles in the infarcted and contralateral hemispheres significantly (P < 0.05) changed at both time-points and were linearly correlated with the mNSS, mBS and some GWT scores (P < 0.001). This correlation allowed for the calculation of simple (linear) mathematical equations (stereotaxic coordinate = b0 + b1 * mNSS, where 'b0' and 'b1' are fixed number and factor, respectively, calculated by regression analysis) that determined individually new coordinates for each animal. Verification experiments revealed that the new coordinates render ICV invasion feasible in up to 80% of infarcted rats (number needed to treat 1.65), compared with only 19.4% using the classical coordinates for normal rats. Therefore, we propose a new, time- and cost-effective methodology for practically feasible ICV invasion in rats 6-18 h after t-MCAO.