Kondo Y, Ogawa N, Asanuma M, Ota Z, Mori A
Department of Neuroscience, Okayama University Medical School, Japan.
J Cereb Blood Flow Metab. 1995 Mar;15(2):216-26. doi: 10.1038/jcbfm.1995.27.
With use of iron histochemistry and immunohistochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein-positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin-eosin staining only in pyramidal cells of the hippocampal CA1 region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3'-diaminobenzidine intensification revealed iron deposits in the CA1 region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin-immunopositive microglia paralleled the iron accumulation in the hippocampal CA1 region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron-catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia.
运用铁组织化学和免疫组织化学方法，在大鼠脑短暂性前脑缺血（四血管闭塞模型）后1至24周，检测铁、铁蛋白、转铁蛋白、胶质纤维酸性蛋白阳性星形胶质细胞以及活化小胶质细胞外观的区域变化。使用C3bi受体和主要组织相容性复合体II类抗原的表达来鉴定小胶质细胞。仅通过苏木精-伊红染色在海马CA1区的锥体细胞中证实神经元死亡，该区域是已知对缺血最敏感的区域。用3,3'-二氨基联苯胺强化的Perls反应显示，4周后CA1区有铁沉积，到24周时逐渐增加并形成簇状。8周后铁也沉积在顶叶皮质的III - V层，并在前额叶皮质V层锥体细胞的细胞质中逐渐积聚形成颗粒状沉积物。海马CA1区铁的积累与星形胶质细胞反应增强和铁蛋白免疫阳性小胶质细胞的出现平行，表明铁沉积可能是在胶质增生过程中产生的。在大脑皮质未发现神经元死亡或萎缩。然而，顶叶皮质在8周时出现星形胶质细胞和铁蛋白免疫阳性小胶质细胞反应。另一方面，在前额叶皮质V层锥体细胞中的颗粒状铁沉积在缺血慢性期未伴有任何胶质细胞反应。本研究显示了短暂性前脑缺血后慢性期三种不同类型的铁沉积。鉴于铁催化自由基形成所导致的神经元损伤，迟发性铁沉积可能与脑缺血后期出现的慢性脑功能障碍的发病机制有关。
