Experimental study of the delayed axonal damages and demyelination in the rat spinal cord after continuous epidural compression

我们采用大鼠脊髓持续压迫模型进行实验研究，以分析慢性压迫性脊髓病的发病机制。用具有缓慢扩张特性的宫颈扩张器Dilapan对大鼠胸段脊髓进行持续硬膜外加压。组织学观察1天至3个月，急性期(7天内)脊髓轻度坏死性改变，多局限于受压部位，未见明显出血性坏死。在白质中，24小时可见水肿，但未见破坏性改变。海绵状改变伴轴索变性持续1~2周，不局限于压迫部位，弥漫性分布于脑白质，持续3个月。组织化学显示脑白质海绵状改变为Wa…2周后S增多伴轴突和髓鞘减少。EM检查显示，侧柱的主要改变是有髓纤维轴突变性，如水肿性肿胀、髓鞘脱离、脱髓鞘、脱髓鞘等。这些轴索病变和脱髓鞘改变已连续出现长达3个月。用抗少突胶质细胞的单抗APC(Ab-7)免疫组织化学染色显示，压迫1周后细胞数量减少，2~4周最明显。TUNEL法检测，24-48小时白质内可见TUNEL阳性细胞，72小时达高峰，说明本实验模型适用于慢性压迫性脊髓病的分析。脑白质出现脱髓鞘改变的持续性轴索病可能是压迫性脊髓病的主要改变。少突胶质细胞的损伤，可能是由于细胞的凋亡性死亡，可能会导致持续压迫后剩余部分的脱髓鞘。较少

We studied experimentally using a spinal cord continuous compression model in rats to analyze the mechanism of chronic compression myelopathy. The rat thoracic spinal cord was epidurally pressured continuously with uterine-cervical dilator Dilapan, which has the character of slow expanding. The lesions were investigated morphologically, by histochemistry, electron microscopy, immunohistochemistry, as well as conventional histology for 1 days to 3 months..Histologically, in acute stage (within 7 days), mildly necrotic changes of the spinal cord occurred, mostly localized in the pressured sites, however, no apparent hemorrhagic necrosis was observed. In the white matter, edema but not destructive changes were seen at 24 hours. The spongy change with axonal degeneration was prominent for 1-2 weeks, which were not localized at the compression site but distributed diffusely in the white matter, continuing for 3 months later. Histochemistry disclosed that the spongy change of white matter wa … More s associated with decrease of axons and myelin 2 weeks later. EM examinations demonstrated that main change in the lateral column was degeneration of axon of myelinated fibers, such as edematous swelling, myelintangles, detachment from myelin sheath, and demyelinated axons. These axonopathy and demyelinating changes had been continuously seen as long as 3 months. Immunnohistochemistry using monoclonal antibody, APC (Ab-7), specific antibody against oligodendrocytes, showed the decrease of the cell number after 1-week compression, and most prominent at 2-4 weeks. Furthermore, by TUNEL examination, TUNEL positive cells were observed in the white matter at 24-48 hours with peak at 72 hours.Tease results indicate that our experimental model is suitable for the analysis of chronic compression myelopathy. The continuous axonopathy with demyelinating changes occurred in the white matter may be the main changes in compression myelopathy. Oligodendrocyte damage, probably due to apoptotic cell death, may cause demyelination of the remaining after continuous compression. Less