Merkler Doron, Klinker Florian, Jürgens Tanja, Glaser Raoul, Paulus Walter, Brinkmann Bastian G, Sereda Michael W, Stadelmann-Nessler Christine, Guedes Rubem C A, Brück Wolfgang, Liebetanz David
Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
Ann Neurol. 2009 Sep;66(3):355-65. doi: 10.1002/ana.21746.
Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD).
CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type I transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein-transgenic mice exhibiting pronounced astrogliosis.
Cortical demyelination, but not astrogliosis or inflammation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type I transgenic mice displayed a decelerated CSD propagation.
Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function.
在中枢神经系统脱髓鞘疾病患者中,皮质髓鞘可能会受到严重影响。然而,皮质脱髓鞘的功能意义仍不清楚。在本研究中,我们调查了皮质髓鞘是否影响皮质扩散性抑制(CSD)。
在毒性和自身免疫诱导的皮质脱髓鞘啮齿动物模型、显示皮质髓鞘增多的神经调节蛋白-1 I型转基因小鼠以及表现出明显星形胶质细胞增生的胶质纤维酸性蛋白转基因小鼠中进行CSD测量。
皮质脱髓鞘,而非星形胶质细胞增生或炎症本身,与CSD加速有关。相反,髓鞘增多的神经调节蛋白-1 I型转基因小鼠显示CSD传播减慢。
皮质髓鞘可能分别对细胞外离子含量的稳定和缓冲至关重要,而细胞外离子含量对CSD传播速度和皮质兴奋性起决定性作用。因此,我们的数据表明,人类脱髓鞘疾病中的皮质受累可能导致皮质功能的相关改变。