Bondan E F, Lallo M A, Sinhorini I L, Pereira L A, Graça D L
University Bandeirante of São Paulo, Brazil.
J Submicrosc Cytol Pathol. 2000 Oct;32(4):603-12.
Long-term cyclophosphamide (CY) treatment was used in male Wistar rats submitted to ethidium bromide (EB) demyelinating model to investigate ultrastructurally the drug effects on remyelination and on central nervous system (CNS) tissue repair. Demyelination was induced by a single 10 microl intracisternal injection of 0.1% EB solution and the rats anaesthetized and perfused through the heart from the 15th to the 31st day after injection. Brainstem sections were collected and processed for light and transmission electron microscopy studies. At different times after EB injection, it was observed the presence of macrophages in phagocytic activity and non-degraded myelin debris in the extracellular space, as well as remyelinated and demyelinated axons. Remyelination was carried out by both oligodendrocytes and Schwann cells, the latter notably around blood vessels and in areas of expanded extracellular space. It was also noted groups of infiltrating meningeal cells and astrocytes showing hypertrophic processes with numerous bundles of glial filaments. The rats treated with CY showed greater amounts of myelin-derived membranes than non-treated rats, suggesting a delay in the macrophage activity of removing myelin debris. Additionally oligodendrocyte remyelinating activity showed an incipient and restricted pattern, with clear predominance of naked axons. Rare lymphocytes were also found, as well as decreased neovascularization.
长期环磷酰胺（CY）治疗应用于接受溴化乙锭（EB）脱髓鞘模型的雄性Wistar大鼠，以超微结构研究该药物对再髓鞘化和中枢神经系统（CNS）组织修复的影响。通过单次脑池内注射10微升0.1% EB溶液诱导脱髓鞘，在注射后第15天至第31天对大鼠进行麻醉并经心脏灌注。收集脑干切片并进行光镜和透射电镜研究。在EB注射后的不同时间，观察到有吞噬活性的巨噬细胞以及细胞外空间中未降解的髓磷脂碎片，还有再髓鞘化和脱髓鞘的轴突。再髓鞘化由少突胶质细胞和施万细胞共同完成，后者尤其在血管周围和细胞外空间扩大的区域。还注意到有浸润的脑膜细胞和星形胶质细胞群，其显示出带有大量胶质丝束的肥大突起。接受CY治疗的大鼠比未治疗的大鼠有更多的髓磷脂衍生膜，这表明巨噬细胞清除髓磷脂碎片的活性延迟。此外，少突胶质细胞的再髓鞘化活性呈现初期且局限的模式，裸轴突明显占优势。还发现了罕见的淋巴细胞，以及新生血管形成减少。
