Delayed axonal degeneration in slow Wallerian degeneration mutant mice detected using diffusion tensor imaging.

Delayed axonal degeneration in slow Wallerian degeneration mutant mice detected using diffusion tensor imaging.
复制标题

使用扩散张量成像检测缓慢沃勒变性突变小鼠的延迟轴突变性。

DOI:
10.1016/j.neuroscience.2011.09.042
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发表时间:
2011-12-01
期刊:
影响因子:
3.3
通讯作者:
Sun, S. -W.
Sun, S. -W.
中科院分区:
医学3区
文献类型:
--
作者:
Xie, M.;Wang, Q.;Wu, T. -H.;Song, S. -K.;Sun, S. -W.

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先前的研究表明,使用弥散张量成像(DTI)作为一种无创成像方式来评估人类和动物的神经变性是可行的。DTI的轴向和径向扩散系数分别被证明是轴突和髓鞘损伤的敏感标志物。本研究采用DTI评价野生型和慢速沃勒氏变性(WldS)突变小鼠视神经变性。高眼压致短暂性视网膜缺血后视神经行纵向DTI。野生型神经轴向弥漫性在短暂性眼压升高后第3天下降30% (P<0.05),第5 ~ 30天下降40% (P<0.05)。相比之下,wld神经的轴向弥漫性在3天后没有变化;短暂性眼压升高后第5天下降了20% (P<0.05),第15天和第30天分别下降了30% (P<0.05)和40% (P<0.05),提示wds小鼠轴突损伤延迟。一过性眼压升高后,野生型小鼠径向弥散度在15-30天增加200% (P<0.05), wds小鼠在30天增加100% (P<0.05),提示wds小鼠髓鞘损伤延迟。DTI检测到的损伤通过免疫组织化学证实,分别使用磷酸化的神经丝和髓鞘碱性蛋白来评估轴突和髓鞘的完整性。这些发现支持DTI不仅用于评估神经退行性变的进展,而且可以无创地证明wld突变可以延缓沃勒氏变性。
Previous studies have shown the feasibility of using diffusion tensor imaging (DTI) as a noninvasive imaging modality to evaluate neurodegeneration in humans and animals. The axial and radial diffusivities derived from DTI were demonstrated to be sensitive markers for axonal and myelin damage, respectively. This study used DTI to evaluate optic nerve degeneration in wild-type and slow Wallerian degeneration (WldS) mutant mice. Longitudinal DTI was performed on optic nerves following high intraocular pressure-induced transient retinal ischemia. The axial diffusivity of wild-type nerves decreased 30% (P<0.05) at 3 days and 40% (P<0.05) at 5–30 days after transient elevation of intraocular pressure. In contrast, the axial diffusivity of WldS nerves did not change at 3 days; decreased by 20% (P<0.05) at 5 days, and continued to decrease by 30% (P<0.05) at 15 days and 40% (P<0.05) at 30 days after transient intraocular pressure elevation, suggesting delayed axonal damage in WldS mice. Radial diffusivity increased 200% (P<0.05) at 15–30 days in the wild-type mice and 100% (P<0.05) at 30 days in the WldS mice after transient intraocular pressure elevation, suggesting delayed myelin damage in WldS mice. DTI detected damage was confirmed with immunohistochemistry using phosphorylated neurofilament and myelin basic protein for assessing axonal and myelin integrity, respectively. These findings support the use of DTI not only to evaluate the progression of neurodegeneration but also to noninvasively demonstrate WldS mutation to delay the Wallerian degeneration.
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