PERMANENT FOCAL AND TRANSIENT GLOBAL CEREBRAL-ISCHEMIA INCREASE GLIALAND NEURONAL EXPRESSION OF HEME OXYGENASE-1, BUT NOT HEME OXYGENASE-2, PROTEIN IN RAT-BRAIN

Two heme oxygenase (HO) proteins have been identified to date; HO-1, a stress-induced protein, and HO-2, a constitutively ex pressed isoform . Recently, it was demonstrated that HO-1 mRNA expression is increased following transient global ischemia. The present study examined the e ffects of global and focal ischemia on HO-I and HO-2 protein, using im munocytochemistry. Following 20 min of ischemia (rat 4 vessel occlusio n model with hypotension) and 6 h of recirculation, increased HO immun oreactivity was evident in hippocampal neurons. After 24 h of recircul ation, HO-1 was observed in both hippocampal neurons and astroglial ce lls. By 72 h, expression was primarily glial and restricted to CAI and CA3c, In addition to hippocampus, HO-1 I was also evident in both neu rons and glia in cerebral cortex and thalamus, and in striatal glial c ells. Twenty-four hours following permanent focal ischemia, HO-1 immun oreactivity was observed in astroglial cells in the penumbra region su rrounding the infarct. In contrast to HO-1, the pattern of HO-2 immuno reactivity was not altered following transient global or permanent foc al ischemia: The increased expression of HO-1 following ischemia may c onfer protection against oxidative stress, but might also contribute t o the subsequent neuronal degeneration.