Suzuki K, Hoogerbrugge P M, Poorthuis B J, Bekkum D W, Suzuki K
Department of Pathology, University of North Carolina, Chapel Hill.
Lab Invest. 1988 Mar;58(3):302-9.
Effects of bone marrow transplantation (BMT) on the pathology of the central nervous system were evaluated, at light and electron microscope levels, in the homozygous twitcher mouse (twi/twi), an authentic murine model of globoid cell leukodystrophy (GLD, Krabbe disease) in humans. In the twitcher mice with BMT examined at ages 44 and 71 days (transplanted at the day 9 to 12), degeneration of oligodendrocytes and myelin was still present. In these mice, oligodendrocytes and macrophages containing typical tubular and crystalloid inclusions of GLD were observed in the white matter, in particular that of the cerebellum, brainstem, and spinal cord. However, significant morphologic improvement was observed in the central nervous system of the twitcher with BMT which survived more than 100 days. In the cerebellum, brainstem, and spinal cord of these mice, myelin degeneration and infiltration of macrophages containing typical GLD inclusions were either absent or only rarely observed. Instead, many foamy macrophages, either scattered or clustered around blood vessels, were conspicuous. Many nerve fibers with thin myelin sheaths indicative of remyelination were present in the white matter. GLD inclusions were, however, still found in the cytoplasm of apparently remyelinating oligodendrocytes. These results suggest that the foamy macrophages are of donor origin, since they are able to digest degraded myelin components completely, because of a sufficient galactosylceramidase activity, and are contributing to the improvement of the central nervous system pathology in the twitcher mouse following BMT, by supplying the deficient enzyme, galactosylceramidase. However, the presence of inclusions in oligodendrocytes in the twitcher with BMT, even after 100 days of age indicates that the basic enzymatic defect involving oligodendrocytes could not be completely corrected with BMT.
在纯合子颤抖小鼠（twi/twi）中，于光镜和电镜水平评估了骨髓移植（BMT）对中枢神经系统病理学的影响，该小鼠是人类球状细胞脑白质营养不良（GLD，克拉伯病）的真实小鼠模型。在44天和71天接受检查的接受BMT的颤抖小鼠（于第9至12天进行移植）中，少突胶质细胞和髓鞘的退化仍然存在。在这些小鼠的白质中，尤其是小脑、脑干和脊髓的白质中，观察到含有GLD典型管状和晶体样内含物的少突胶质细胞和巨噬细胞。然而，在存活超过100天的接受BMT的颤抖小鼠的中枢神经系统中观察到了显著的形态学改善。在这些小鼠的小脑、脑干和脊髓中，髓鞘退化以及含有典型GLD内含物的巨噬细胞浸润要么不存在，要么仅很少观察到。相反，许多泡沫状巨噬细胞，要么分散要么聚集在血管周围，十分明显。白质中存在许多具有薄髓鞘的神经纤维，表明有髓鞘再生。然而，在明显正在进行髓鞘再生的少突胶质细胞的细胞质中仍发现有GLD内含物。这些结果表明，泡沫状巨噬细胞源自供体，因为它们能够由于足够的半乳糖基神经酰胺酶活性而完全消化降解的髓鞘成分，并且通过提供缺乏的酶——半乳糖基神经酰胺酶，有助于改善接受BMT后的颤抖小鼠的中枢神经系统病理学。然而，即使在100日龄之后，接受BMT的颤抖小鼠少突胶质细胞中仍存在内含物，这表明涉及少突胶质细胞的基本酶缺陷不能通过BMT完全纠正。
