Harsan Laura A, Poulet Patrick, Guignard Blandine, Steibel Jérôme, Parizel Nathalie, de Sousa Paulo Loureiro, Boehm Nelly, Grucker Daniel, Ghandour M Said
UMR 7004 CNRS/ULP, Institut de Physique Biologique, Faculté de Médecine,Université Louis Pasteur, Strasbourg, France.
J Neurosci Res. 2006 Feb 15;83(3):392-402. doi: 10.1002/jnr.20742.
Diffusion tensor magnetic resonance imaging (DT-MRI) was applied for in vivo quantification of myelin loss and regeneration. A transgenic mouse line (Oligo-TTK) expressing a truncated form of the herpes simplex virus 1 thymidine kinase gene (hsv1-tk) in oligodendrocytes was studied along with two induced phenotypes of myelin pathology. Myelin loss and axonal abnormalities differentially affect values of DT-MRI parameters in the brain of transgenic mice. Changes in the anisotropy of the white matter were assessed by calculating and mapping the radial (D perpendicular) and axial (D parallel) water diffusion to axonal tracts and fractional anisotropy (FA). A significant increase in D perpendicular attributed to the lack of myelin was observed in all selected brain white matter tracts in dysmyelinated mice. Lower D parallel values were consistent with the histological observation of axonal modifications, including reduced axonal caliber and overexpression of neurofilaments and III beta-tubulin. We show clearly that myelination and axonal changes play a role in the degree of diffusion anisotropy, because FA was significantly decreased in dysmyelinated brain. Importantly, myelin reparation during brain postnatal development induced a decrease in the magnitude of D( perpendicular) and an increase in FA compared with the same brain before recovery. The progressive increase in D parallel values was attributed to the gain in normal axonal morphology. This regeneration was confirmed by the detection of enlarged oligodendrocyte population, newly formed myelin sheaths around additional axons, and a gradual increase in axonal caliber.
扩散张量磁共振成像（DT-MRI）被用于体内髓鞘损失和再生的定量分析。研究了一种在少突胶质细胞中表达截短形式单纯疱疹病毒1胸苷激酶基因（hsv1-tk）的转基因小鼠品系（Oligo-TTK）以及两种髓鞘病理诱导表型。髓鞘损失和轴突异常对转基因小鼠大脑中DT-MRI参数值有不同影响。通过计算并绘制径向（D垂直）和轴向（D平行）水扩散到轴突束以及分数各向异性（FA）来评估白质各向异性的变化。在髓鞘发育异常的小鼠所有选定的脑白质束中，观察到由于髓鞘缺乏导致D垂直显著增加。较低的D平行值与轴突改变的组织学观察结果一致，包括轴突直径减小以及神经丝和IIIβ-微管蛋白的过度表达。我们清楚地表明，髓鞘形成和轴突变化在扩散各向异性程度中起作用，因为在髓鞘发育异常的大脑中FA显著降低。重要的是，与恢复前的同一大脑相比，脑产后发育过程中的髓鞘修复导致D（垂直）值减小以及FA增加。D平行值的逐渐增加归因于正常轴突形态的恢复。通过检测增大的少突胶质细胞群体、额外轴突周围新形成的髓鞘以及轴突直径的逐渐增加，证实了这种再生。
