Politis M J, Houle J D
Brain Res. 1985 Mar 4;328(2):291-300. doi: 10.1016/0006-8993(85)91041-8.
Glial reactivity is believed to contribute to the lack of functional recovery after injury to the mammalian central nervous system. The role of glial mitosis in the progression of events associated with reactive gliosis has received little attention. In the present study, the expression of reactive gliosis distal to the site of crush in rat optic nerves was assessed in the presence and absence of a chronically administered mitotic inhibitor, cytosine arabinofuranoside (AraC). Right optic nerves were crushed and animals sacrificed 1, 2 or 3 weeks later. Parameters assessed were (1) glial hypertrophy, (2) degradation of myelin sheaths and (3) ability of tissue to stain with antisera raised against glial filament protein (GFA), actin and vimentin. In saline treated animals, greater than 90% of the myelin sheaths distal to the site of axonal injury had degraded within 7 days postoperatively. Glial hypertrophy was evident by the second week after after crush and increased progressively. The number of GFA-positive profiles (i.e., cells) increased between 1 and 3 weeks postoperatively. Vimentin staining increased 4-fold between 1 and 2 weeks after injury and subsequently showed no change. Actin staining rose 3-fold between 1 and 2 weeks after injury, but decreased by the third postoperative week. In AraC treated animals, almost 50% of the myelin sheaths distal to the injury site were preserved a week after surgery. A delay in myelin degradation continued until the second postoperative week. Glial hypertrophy was evident at the 2 and 3 week time points. However, the extent of hypertrophy was substantially lower in drug (vs saline) treated animals. Vimentin staining never rose above minimal levels in AraC treated animals. Actin staining in AraC rats at 2 weeks postoperatively was equivalent to that in saline injected animals, but in contrast to the results in the latter group, increased (3-fold) between 2 and 3 weeks after crush. Results indicate a delay in the expression of reactive gliosis with chronic administration of AraC. It is proposed that this might be due to a delay in the appearance of 'signals' (e.g., myelin debris) which initiate the process of reactive gliosis.
人们认为胶质细胞反应性是哺乳动物中枢神经系统损伤后功能恢复欠佳的原因之一。胶质细胞有丝分裂在与反应性胶质增生相关的一系列事件进展中的作用很少受到关注。在本研究中，在长期给予有丝分裂抑制剂阿糖胞苷（AraC）和未给予该抑制剂的情况下，评估大鼠视神经挤压部位远端的反应性胶质增生的表达情况。右侧视神经被挤压，在1、2或3周后处死动物。评估的参数包括：（1）胶质细胞肥大；（2）髓鞘降解；（3）组织用抗胶质纤维酸性蛋白（GFA）、肌动蛋白和波形蛋白的抗血清染色的能力。在生理盐水处理的动物中，轴突损伤部位远端90%以上的髓鞘在术后7天内已降解。挤压后第二周胶质细胞肥大明显，并逐渐增加。术后1至3周，GFA阳性细胞数量增加。波形蛋白染色在损伤后1至2周增加了4倍，随后没有变化。肌动蛋白染色在损伤后1至2周增加了3倍，但在术后第三周下降。在AraC处理的动物中，损伤部位远端近50%的髓鞘在手术后一周得以保留。髓鞘降解延迟持续到术后第二周。在第2和第3周时间点胶质细胞肥大明显。然而，药物（与生理盐水相比）处理的动物中肥大程度明显较低。在AraC处理的动物中，波形蛋白染色从未超过最低水平。AraC处理的大鼠术后2周的肌动蛋白染色与注射生理盐水的动物相当，但与后一组结果相反，在挤压后2至3周增加（3倍）。结果表明，长期给予AraC会延迟反应性胶质增生的表达。据推测，这可能是由于启动反应性胶质增生过程的“信号”（如髓鞘碎片）出现延迟所致。
