LONG-TERM INDUCTION OF HEME OXYGENASE-1 (HSP-32) IN ASTROCYTES AND MICROGLIA FOLLOWING TRANSIENT FOCAL BRAIN ISCHEMIA IN THE RAT

Haem oxygenase-1 (HO-1) is a stress protein and a rate-limiting enzyme in haem degradation, generating ferrous iron, carbon monoxide and bil e pigments. HO-1 has been suggested to be protective against oxidative stress. In the normal rodent brain the enzyme is localized in selecte d neuron populations, but heat shock, glutathione depletion in vivo an d oxidative stress in vitro induce HO-1 predominantly in glial cells. We studied HO-1 expression in the brain following transient occlusion of the middle cerebral artery, and found increased mRNA levels in the ischaemic region from 4 h to 7 days after 90 min of ischaemia. The mRN A levels peaked at 12 h, and were localized perifocally. HO-1-immunore active astrocytes and microglial cells were seen in the perifocal area , in the ipsilateral and occasionally in the contralateral hippocampus . Some perifocal neurons were also HO-1-immunoreactive. In the infarct ed area HO-1-positive microglia/macrophages were detected in double-la belling experiments. A microassay measuring the conversion of [C-14]ha em to [C-14]bilirubin showed a two-fold increase in haem oxygenase act ivity in the infarcted core. These observations show a long-term induc tion of HO-1 protein and its activity following ischaemia-reperfusion brain injury, and indicate increased capacity for haem degradation and the generation of biologically active bile products, carbon monoxide and iron in astrocytes and some microglia/macrophages during focal bra in ischaemia.