Dubois A, Bénavidès J, Peny B, Duverger D, Fage D, Gotti B, MacKenzie E T, Scatton B
Laboratoires d'Etudes et de Recherches Synthélabo, Bagneux, France.
Brain Res. 1988 Mar 29;445(1):77-90. doi: 10.1016/0006-8993(88)91076-1.
Seven days after unilateral middle cerebral artery occlusion in rats, peripheral type benzodiazepine binding sites (PTBBS), using [3H]PK 11195 as a specific radioligand, were greatly increased in the cortical and striatal regions surrounding the focus of infarction with smaller increases in the ventrolateral and posterior thalamic complexes and in the substantia nigra, all ipsilateral to the occlusion. Similarly, PTBBS increases were observed in the caudate nucleus and entorhinal cortex of cats likewise subjected to prior unilateral occlusion of the middle cerebral artery. Intrastriatal administration of N-methyl-D-aspartate (250 nmol) in the rat resulted in a dramatic ipsilateral increase in PTBBS levels in the striatum and in the deeper laminae of the ipsilateral frontoparietal cortex. Intrastriatal kainic acid administration (12 nmol) also elicited PTBBS increases ipsilaterally in rat striatum and cortex; a bilateral elevation of PTBBS levels was observed in the hippocampus. With all these interventions there existed a good spatial correlation between the PTBBS increase and neuronal loss as assessed either histologically or by the autoradiographic detection of the putative neuronal marker [3H]SCH 23390 (a D1 dopamine receptor ligand). Moreover, a glial proliferation of non-neuronal cells (macrophage and glial cells) was observed in brain regions noted to have increased PTBBS levels. PTBBS autoradiography thus constitutes a suitable technique for the localization of damaged areas in several experimental models of brain injury. PTBBS label not only the primary lesions but also functionally related areas and could further our understanding of phenomena such as partial neuronal loss and diaschisis. The study of PTBBS could be envisaged for the detection, localization and quantification of all neuropathological situations which engender a glial reaction or macrophage invasion and is potentially applicable to both experimental and human subjects, in which both autoradiographic and tomographic approaches could be undertaken.
在大鼠单侧大脑中动脉闭塞7天后，使用[3H]PK 11195作为特异性放射性配体检测发现，梗死灶周围的皮质和纹状体区域外周型苯二氮䓬结合位点（PTBBS）大幅增加，而丘脑腹外侧和后复合体以及黑质中增加幅度较小，所有这些均位于闭塞同侧。同样，在事先进行过单侧大脑中动脉闭塞的猫的尾状核和内嗅皮质中也观察到PTBBS增加。在大鼠纹状体内注射N-甲基-D-天冬氨酸（250 nmol）导致纹状体以及同侧额顶叶皮质深层中PTBBS水平显著同侧增加。纹状体内注射 kainic 酸（12 nmol）也引起大鼠纹状体和皮质同侧PTBBS增加；在海马体中观察到PTBBS水平双侧升高。通过所有这些干预措施，PTBBS增加与神经元丢失之间存在良好的空间相关性，这是通过组织学评估或通过对假定的神经元标记物[3H]SCH 23390（一种D1多巴胺受体配体）的放射自显影检测来评估的。此外，在PTBBS水平升高的脑区观察到非神经元细胞（巨噬细胞和神经胶质细胞）的胶质细胞增殖。因此，PTBBS放射自显影术是在几种脑损伤实验模型中定位受损区域的合适技术。PTBBS不仅标记原发性病变，还标记功能相关区域，并且可以加深我们对诸如部分神经元丢失和神经机能联系失能等现象的理解。对PTBBS的研究可设想用于检测、定位和量化所有引发胶质细胞反应或巨噬细胞侵袭的神经病理学情况，并且可能适用于实验对象和人类受试者，在其中可以采用放射自显影和断层扫描方法。
