Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis
Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis
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DOI：
10.1093/brain/123.9.1845
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发表时间：
2000-09-01
期刊：
影响因子：
14.5
通讯作者：
Matthews, PM
中科院分区：
文献类型：
--
作者：
Evangelou, N;Konz, D;Matthews, PM
先前的成像研究已经表明，在多发性硬化症患者的大脑的正常外观的白色物质（NAWM）中存在大量的轴突损失，并且这种轴突损失可能是残疾的重要决定因素。最近，NAWM中的大量轴突损失已经直接在死后组织中得到证实，NAWM的变化是否是由于穿过病变的轴突损伤或更弥漫性的损伤过程的结果尚不确定，使用福尔马林固定的8名多发性硬化患者和8名年龄匹配的对照者的大脑，我们检查了三个体积的大脑白色物质中脱髓鞘病变负荷与相应三个投射区域NAWM中轴突损失之间的关系与非多发性硬化对照组相比，胼胝体（CC）前、中、后三个区域中穿过CC的轴突总数均显著减少，区域损伤负荷与轴突密度之间存在强相关性。（r =-0.673，P = 0.001）和穿过CC中相应投射区域的轴突总数的估计值（r =-0.656，P = 0.001），这表明在脱髓鞘病变中横断的轴突的沃勒变性对多发性硬化中NAWM中轴突的大量弥漫性损失做出了主要贡献，这些研究结果强调，需要考虑多发性硬化病变的后果，在功能连接的大脑区域的本地和远程的影响。
Previous imaging studies have suggested that there is substantial axonal loss in the normal-appearing white matter (NAWM) of brains from multiple sclerosis patients and that this axonal loss may be an important determinant of disability, Recently, substantial axonal loss in the NAWM has been confirmed directly in postmortem tissue, Whether the NAWM changes occur as a consequence of damage to axons traversing lesions or to a more diffuse injury process is uncertain, Using formalin-fixed brains of eight multiple sclerosis patients and eight age-matched controls, we examined the relationship between demyelinating lesion load in three volumes of the cerebral white matter and the loss of axons in NAWM of the corresponding three projection regions (anterior, middle, posterior) in the corpus callosum (CC), There was a significant loss of calculated total number of axons crossing the CC in each of the three regions relative to the non-multiple sclerosis controls, Strong correlations were found between the regional lesion load and both the axonal density (r = -0.673, P = 0.001) and the total estimated number of axons crossing the corresponding projection area in the CC (r = -0.656, P = 0.001) for the patients, This suggests that Wallerian degeneration of axons transected in the demyelinating lesions makes a major contribution to the substantial, diffuse loss of axons in the NAWM in multiple sclerosis, These findings emphasize the need to consider the consequences of multiple sclerosis lesions in terms of both local and distant effects in functionally connected regions of the brain.