A neuropathological approach for pathogenesis of onion-bulb formation after acute axonal degeneration in an animal model.

为了研究MSR在体内髓鞘吞噬中的作用，(1)我们对野生型和MSR a类（MSR- a）敲除（ko）小鼠的坐骨神经进行单一压迫损伤，(2)我们用异烟肼（INH）麻醉ko小鼠，并在压迫或中毒21天后检查神经。形态计量学研究表明，野生型小鼠和MSR-A - ko小鼠剩余髓鞘纤维的平均密度从未压缩时的约22000/mm^22降低到压缩后的7500-10000/mm^2，野生型小鼠和ko小鼠之间无显著差异。在压迫部位最突出的病理特征是MSR-A - ko小鼠形成了许多小洋葱球（OBs），而野生型小鼠则很少。使用抗氧化磷脂酰胆碱的抗体，ko小鼠的髓磷脂及其碎片在受压神经纤维内和周围的染色比野生型小鼠更密集，尽管未受压的神经纤维根本没有染色。与野生型小鼠相比，在ko小鼠中发现了更多的泡沫细胞。尽管抗氧化磷脂酰胆碱抗体免疫组化染色显示神经内膜弥漫性染色，但在INH中毒后，部分ko小鼠的坐骨神经表现出与压迫时相似的变化。根据这些结果，我们得出结论：1)神经压迫和INH中毒后髓鞘产生氧化磷脂；2)MSR可能在清除受损细胞膜（包括髓鞘紊乱）中发挥重要作用；3)MSR功能障碍是OB形成的原因。

To investigate the role of the MSR in myelin phagocytosis in vivo, (1) we produced a single compression lesion to sciatic nerves of both wild-type and MSR class A (MSR-A) knockout (ko) mice, (2) we intoxicated ko mice with isoniazid (INH), and examined the nerves 21 days after compression or intoxication. A morphometric study showed that the average densities of remaining myelinated fibers in wild-type mice and MSR-A ko mice were reduced from about 22000/mm^22 without compression to 7500-10000/mm^2 after compression, with no significant difference between the wild-type and ko mice. The most prominent pathological feature at the compression site was formation of many small onion-bulbs (OBs) in the MSR-A ko mice, whereas the wild-type mice showed only few. With an antibody against oxidized phosphatidylcholine, myelin and its debris in and around compressed nerve fibers were more densely stained in the ko mice than in the wild-type mice, although non-compressed nerve fibers were not stained at all. Foamy cells were identified more in the ko mouse as compared to the wild-type mouse. After INH intoxication, some of the ko mice showed similar changes in their sciatic nerves as in the compression, although immunohistochemical staining with anti-oxidized phosphatidylcholine antibody showed more diffusely stained endoneurium. From these results, we conclude that 1) oxidized phospholipids was generated from the myelin sheath after a nerve compression and INH intoxication, 2) the MSR might have played an important role in scavenging damaged cell membranes including the myelin aheath, and 3) dysfunction of the MSR was responsible for OB formation.