TEMPORAL CHANGES IN GLIAL FIBRILLARY ACIDIC PROTEIN MESSENGER-RNA AND[H-3] PK11195 BINDING IN RELATION TO IMIDAZOLINE-I-2-RECEPTOR AND ALPHA(2)-ADRENOCEPTOR BINDING IN THE HIPPOCAMPUS FOLLOWING TRANSIENT GLOBAL FOREBRAIN ISCHEMIA IN THE RAT

Immunohistochemical studies have demonstrated that following global fo rebrain ischaemia the selective neuronal loss that occurs in the CA1 p yramidal cell layer of the hippocampus is accompanied by a reactive as trocytosis, characterized by increases in glial fibrillary acidic prot ein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocamp us have been mapped four, eight, 12, 16 and 20 days following 10 min o f global forebrain ischaemia in the rat and related to changes in [H-3 ]PK11195 binding to peripheral benzodiazepine receptors, a putative ma rker of activated microglia. Recent studies have suggested that the im idazoline-I-2-receptor, one of a class of non-adrenergic receptors rel ated to, but structurally and functionally distinct from alpha(2)-adre noceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I-2-receptor and alpha(2)-a drenoceptor binding sites. Following transient ischaemia there was a m arked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, pe aking four days after ischaemia and then increasing gradually during t he remainder of the study period. There was also a sustained increase in [H-3]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked fo ur days after ischaemia the density of [H-3]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marke d increase in glial fibrillary acidic protein messenger RNA levels the re was no concomitant alteration in imidazoline-I-2-receptor binding s ites detected using the specific radioligand, [H-3]2-(2-benzofuranyl)- 2-imidazoline, although alpha(2)-adrenoceptor binding was decreased al eight days after ischaemia and did not recover. The time-course and b iphasic nature of the changes in the astrocytic marker, glial fibrilla ry acidic protein messenger RNA, in the hippocampus following ischaemi a may reflect different functions of glial fibrillary acidic protein-r eactive astrocytes in the post-ischaemic period. Differences in tempor al expres sion of glial fibrillary acidic protein messenger RNA and [H -3]PK11195 binding support the proposed localization of peripheral ben zodiazepine receptors on activated microglia, as distinct from reactiv e astrocytes. There was no evidence in the present study that imidazol ine I-2-receptors are functionally linked to glial fibrillary acidic p rotein expression as the reactive astrocytosis in the hippocampus foll owing ischaemia was not associated with changes in imidazoline-I-2-rec eptor binding site density. (C) 1997 IBRO.