Horsburgh K, Nicoll J A
Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, UK.
Neuropathol Appl Neurobiol. 1996 Aug;22(4):342-9. doi: 10.1111/j.1365-2990.1996.tb01113.x.
The aim of this study was to examine the cellular localization and alterations of apolipoprotein E (apoE) following a transient ischaemic insult using immunohistochemistry. Transient cerebral ischaemia was induced in Wistar rats by occlusion of both carotid arteries with hypotension followed by reperfusion for 4 h (n = 5), 24 h (n = 5) or 72 h (n = 6). In sham-operated animals (n = 9), the carotids were not occluded. In this model, ischaemia for 15 min results in selective neuronal damage in the caudate nucleus and neocortex (24 h after reperfusion) and the hippocampal CA1 pyramidal cells (72 h after reperfusion) while there is minimal damage in other areas such as the CA3 hippocampal region. In sham animals apoE immunoreactivity was confined to astrocytes and their processes. ApoE immunoreactivity was not altered at 4 h post-ischemic reperfusion. At 24 h reperfusion, intense apoE staining of the cytoplasm of astrocytes and neuropil within the caudate and neocortex was observed and at 72 h reperfusion apoE stained neuronal cell bodies within these regions. Within the CA1 region at 24 h reperfusion, there was increased immunoreactivity of the cytoplasm of astrocytes and the neuropil was more intensely stained compared with sham animals. At 72 h reperfusion, intense apoE staining of pyramidal cell bodies and dendrites was consistently observed in the CA1 region of the hippocampus. In contrast, at 72 h reperfusion, apoE staining of astrocytic processes was dramatically reduced in the CA1 region although GFAP staining indicated their preservation. The results demonstrate that following an ischaemic insult apoE is localized to degenerating neurons and their processes. This may indicate an inherent protective response of cells to injury. Alternatively, the results are consistent with the hypothesis that apoE is synthesized and released by astrocytes and taken up by neurons following injury.
本研究的目的是利用免疫组织化学方法检测短暂性缺血损伤后载脂蛋白E（apoE）的细胞定位及变化。通过双侧颈动脉闭塞并伴有低血压，随后再灌注4小时（n = 5）、24小时（n = 5）或72小时（n = 6），在Wistar大鼠中诱导短暂性脑缺血。在假手术动物（n = 9）中，颈动脉未闭塞。在该模型中，缺血15分钟会导致尾状核和新皮质（再灌注后24小时）以及海马CA1锥体细胞（再灌注后72小时）出现选择性神经元损伤，而在其他区域如海马CA3区损伤极小。在假手术动物中，apoE免疫反应性局限于星形胶质细胞及其突起。缺血再灌注后4小时，apoE免疫反应性未发生改变。再灌注24小时时，观察到尾状核和新皮质内星形胶质细胞胞质和神经纤维网有强烈的apoE染色，再灌注72小时时，这些区域的神经元细胞体被apoE染色。在再灌注24小时时，CA1区域内星形胶质细胞胞质的免疫反应性增强，与假手术动物相比，神经纤维网染色更强烈。再灌注72小时时，在海马CA1区域持续观察到锥体细胞体和树突有强烈的apoE染色。相比之下，再灌注72小时时，尽管GFAP染色显示星形胶质细胞突起保存，但CA1区域星形胶质细胞突起的apoE染色显著减少。结果表明，缺血损伤后apoE定位于退变的神经元及其突起。这可能表明细胞对损伤的一种内在保护反应。或者，这些结果与apoE由星形胶质细胞合成并释放，损伤后被神经元摄取的假说一致。
