Differential regulation of ciliary neurotrophic factor and its receptor inthe rat hippocampus following transient global ischemia

To investigate a potential role of ciliary neurotrophic factor (CNTF) in tr ansient global ischemia, we have studied the postischemic regulatory change s in the expression of CNTF and its receptor, the ligand-binding or-subunit (CNTFR alpha). Immunoblot analysis demonstrated CNTF levels were slightly upregulated already during the first day after ischemia and then increased markedly by more than 10-fold until 2 weeks postischemia. Immunoreactivity for CNTF became detectable 1 day after ischemia and was localized in reacti ve astrocytes. The intensity of the immunolabeling was maximal in CAI durin g the phase of neuronal cell death (days 3-7 postischemia) and in the deaff erented inner molecular layer of the dentate gyrus. Upregulation of CNTF ex pression was less pronounced in CA3 and absent in the stratum lacunosum mol eculare and the outer molecular layer of the dentate gyrus and thus did not simply correlate with astroliosis as represented by upregulation of glial fibrillary acidic protein (GFAP). As shown by in situ hybridization, expres sion of CNTFRa mRNA was restricted to neurons of the pyramidal cell and gra nule cell layers in control animals. Following ischemia, reactive astrocyte s, identified by double labeling with antibodies to GFAP, transiently expre ssed CNTFRa mRNA with a maximum around postischemic day 3. This astrocytic response was most pronounced in CA1 and in the hilar part of CA3. These res ults show that CNTF and its receptor are differentially regulated in activa ted astrocytes of the postischemic hippocampus, indicating that they are in volved in the regulation of astrocytic responses and the neuronal reorganiz ations occurring after an ischemic insult. (C) 2000 Elsevier Science B.V. A ll rights reserved.