Brain white matter is the means of efficient signal propagation in brain and its dysfunction is associated with many neurological disorders. We studied the effect of hyaluronan deficiency on the integrity of myelin in murine corpus callosum. Conditional knockout mice lacking the hyaluronan synthase 2 were compared with control mice. Ultrastructural analysis by electron microscopy revealed a higher proportion of myelin lamellae intruding into axons of knockout mice, along with significantly slimmer axons (excluding myelin sheath thickness), lower g-ratios, and frequent loosening of the myelin wrappings, even though the myelin thickness was similar across the genotypes. Analysis of extracellular diffusion of a small marker molecule tetramethylammonium (74 MW) in brain slices prepared from corpus callosum showed that the extracellular space volume increased significantly in the knockout animals. Despite this vastly enlarged volume, extracellular diffusion rates were significantly reduced, indicating that the compromised myelin wrappings expose more complex geometric structure than the healthy ones. This finding was confirmed in vivo by diffusion-weighted magnetic resonance imaging. Magnetic resonance spectroscopy suggested that water was released from within the myelin sheaths. Our results indicate that hyaluronan is essential for the correct formation of tight myelin wrappings around the axons in white matter.

脑白质是大脑中有效信号传播的手段，其功能障碍与许多神经系统疾病有关。我们研究了透明质酸缺乏对小鼠体髓鞘完整性的影响。将缺乏透明质酸合酶2的条件敲除小鼠与对照小鼠进行比较。通过电子显微镜进行的超微结构分析显示，侵入到基因敲除小鼠轴突中的髓鞘片比例更高，同时轴突显着变薄（不包括髓鞘厚度），较低的g-比值，以及髓鞘包裹物经常松动，即使髓鞘厚度为在基因型上相似。分析小标记分子四甲基铵（74 MW）在用from体制备的脑切片中的细胞外扩散，结果表明，基因敲除动物的细胞外空间体积显着增加。尽管体积大大增加，但细胞外扩散速率却显着降低，表明受损的髓鞘包裹物比健康包裹物暴露出更复杂的几何结构。通过扩散加权磁共振成像在体内证实了这一发现。磁共振波谱表明水从髓鞘内释放。我们的结果表明，透明质酸对于在白质轴突周围正确形成紧密的髓鞘包裹至关重要。细胞外扩散率显着降低，表明受损的髓鞘包裹物比健康的髓鞘包裹物暴露出更复杂的几何结构。通过扩散加权磁共振成像在体内证实了这一发现。磁共振波谱表明，髓鞘内释放出水。我们的结果表明，透明质酸对于在白质轴突周围正确形成紧密的髓鞘包裹至关重要。细胞外扩散率显着降低，表明受损的髓鞘包裹物比健康的髓鞘包裹物暴露出更复杂的几何结构。通过扩散加权磁共振成像在体内证实了这一发现。磁共振波谱表明，髓鞘内释放出水。我们的结果表明，透明质酸对于在白质轴突周围正确形成紧密的髓鞘包裹至关重要。