Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "C. Besta", via Celoria 11, 20133 Milan, Italy.
Neuroscience. 2011 Sep 29;192:564-71. doi: 10.1016/j.neuroscience.2011.07.009. Epub 2011 Jul 18.
The 1-3-bis-chloroethyl-nitrosurea (BCNU)-treated rats represent a good model of cortical dysplasia (CD), as proved by the presence of some histological alterations similar to those observed in human CD, including cortical thinning, laminar disorganization, and heterotopia. The cortical cytoarchitectonics of BCNU-treated rats has been widely investigated by means of histological procedures, immunocytochemistry, and in situ hybridization techniques, implying the sacrifice of the animals. With the aim of identifying brain alterations in vivo to have the possibility of performing longitudinal studies, we used both conventional T(2)-weighted magnetic resonance imaging (MRI) and manganese-enhanced MRI (MEMRI). Though the T(2)-weighted MRI showed the gross anatomical landmarks of BCNU-treated rats, only following Mn(2+) administration T(1)-weighted MRI did reveal the brain cytoarchitectonics both of control and BCNU-treated rats. In particular, changes in MEMRI signal depicted the laminar architecture of control rats while BCNU-treated cortex showed no appreciable changes in MEMRI contrast, consistent with their abnormal cortical lamination. Furthermore, in the treated animals MEMRI revealed hyperintense signals corresponding to heterotopia, as shown by the comparison between MEMRI images and Thionin staining and calbindin immunocytochemistry from the same animals. The qualitative findings obtained with MEMRI were semi-quantitatively confirmed by image segmentation of grey matter. Overall, these data show that MEMRI can be used as a non-invasive technique to investigate cortical alterations in animal models of CD in vivo, giving the possibility to perform longitudinal studies, such as electrophysiological recordings or behavioural investigations.
1,3-双(氯乙基)-亚硝脲(BCNU)处理的大鼠表现出皮质发育不良(CD)的良好模型，这一点已被证明，因为存在一些与人类 CD 观察到的相似的组织学改变，包括皮质变薄、层状结构紊乱和异位。BCNU 处理的大鼠的皮质细胞结构已通过组织学程序、免疫细胞化学和原位杂交技术进行了广泛研究，这意味着需要牺牲动物。为了在体内识别脑改变，以便有可能进行纵向研究，我们同时使用了常规 T2 加权磁共振成像 (MRI) 和锰增强 MRI (MEMRI)。尽管 T2 加权 MRI 显示了 BCNU 处理大鼠的大体解剖标志，但只有在 Mn2+给药后，T1 加权 MRI 才显示了对照组和 BCNU 处理组大鼠的脑细胞结构。特别是，MEMRI 信号的变化描绘了对照组大鼠的层状结构，而 BCNU 处理的皮质在 MEMRI 对比中没有明显变化，与它们异常的皮质分层一致。此外，在处理后的动物中，MEMRI 显示出与异位相一致的高信号，这可以通过将 MEMRI 图像与来自同一动物的 Thionin 染色和钙结合蛋白免疫细胞化学进行比较来证明。MEMRI 获得的定性结果通过灰质的图像分割得到了半定量确认。总的来说，这些数据表明 MEMRI 可作为一种非侵入性技术，用于在体内研究 CD 动物模型的皮质改变，并有可能进行纵向研究，如电生理记录或行为研究。
