Stephenson D T, Schober D A, Smalstig E B, Mincy R E, Gehlert D R, Clemens J A
Eli Lilly and Company, CNS Division, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
J Neurosci. 1995 Jul;15(7 Pt 2):5263-74. doi: 10.1523/JNEUROSCI.15-07-05263.1995.
In mammalian brain the expression of peripheral benzodiazepine receptors (PBRs) can be markedly induced following different types of neuronal injury. PBRs are believed to be expressed on non-neuronal cells in the brain, yet the specific cell type that expresses these receptors following CNS insult has not been defined. In the present study, we investigated the effects of transient global forebrain ischemia on PBRs by autoradiographic localization of 3H-PK11195 binding. The distribution of PBRs was compared to glial fibrillary acidic protein (GFAP) as a marker for astrocytes and OX42 as a marker for microglia. Five to 6 d following four-vessel occlusion (4-VO), an increase in PBRs was seen in the CA1 region of all 15 brains examined. In brains from rats subjected to 4-VO, microglia were selectively activated in stratum pyramidale of the CA1 layer. In contrast, astrocytes appeared to be activated in multiple hippocampal cell layers including stratum radiatum and stratum oriens. Activated astrocytes were also found in regions that did not exhibit increased 3H-PK11195 binding. In some brains, selected regions of secondary lesion, specifically necrotic thalamic nuclei and the isocortex were found to be strongly immunoreactive for OX42 but lacked GFAP immunoreactive cells. In adjacent sections, these same regions displayed high densities of 3H-PK1195 binding. These observations lend further support to the application of 3H-PK11195 binding as a marker of neuronal injury in the brain. Furthermore, the data strongly suggest that activated microglia rather than astrocytes express PBRs following ischemic insults.
在哺乳动物大脑中，不同类型的神经元损伤后可显著诱导外周苯二氮䓬受体（PBRs）的表达。PBRs被认为在大脑中的非神经元细胞上表达，但中枢神经系统损伤后表达这些受体的特定细胞类型尚未明确。在本研究中，我们通过3H-PK11195结合的放射自显影定位研究了短暂性全脑缺血对PBRs的影响。将PBRs的分布与作为星形胶质细胞标志物的胶质纤维酸性蛋白（GFAP）以及作为小胶质细胞标志物的OX42进行了比较。四动脉闭塞（4-VO）后5至6天，在所检查的所有15个大脑的CA1区域均可见PBRs增加。在接受4-VO的大鼠大脑中，小胶质细胞在CA1层的锥体层被选择性激活。相比之下，星形胶质细胞似乎在包括辐射层和原层在内的多个海马细胞层中被激活。在未表现出3H-PK11195结合增加的区域也发现了活化的星形胶质细胞。在一些大脑中，发现继发性病变的选定区域，特别是坏死的丘脑核和异皮质，对OX42有强烈的免疫反应，但缺乏GFAP免疫反应性细胞。在相邻切片中，这些相同区域显示出高密度的3H-PK1195结合。这些观察结果进一步支持了将3H-PK11195结合用作大脑神经元损伤标志物的应用。此外，数据强烈表明，缺血性损伤后，活化的小胶质细胞而非星形胶质细胞表达PBRs。
