Heme oxygenase-1 (HSP-32) and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis

Cerebral ischemic injury results in the liberation of heme from degeneratin g heme-containing proteins. The neurotoxic heme is usually detoxified by th e constitutive heme oxygenase-a (HO-2) and its inducible isoform HO-l(heat shock protein 32) resulting in the formation of biliverdin which becomes re duced to bilirubin, carbon monoxide (CO), and iron. Biliverdin and bilirubi n have antioxidative properties whereas CO is discussed as a signaling mole cule, Iron if it remains free could catalyze Haber-Weiss and Fenton reactio ns causing the formation of highly toxic radicals, We have studied the alte rations of cerebral HO-2 and HO-1 in relation to iron accumulations after d efined cortical photothrombosis within the hindlimb area of the rat. HO-2 i mmunohistochemistry showed that the number of HO-2-positive neurons in most perilesional regions remained constant. However, much stronger systemic im munoreactivity for HO-2 was observed between days 1 and 7 postlesion, For H O-1 a systemic increase of immunoreactivity occurred also between days 1 an d 7, In addition HO-1-positive astrocytes and microglia appeared as early a s 4 h postlesion and increased up to day 3 followed by a sharp decline towa rd day 14 within the injured hemisphere. HO-1-positive astrocytes and micro glia occurred in ipsilateral cortex, corpus callosum, hippocampus, striatum , and thalamic nuclei, Additionally an increase of HO-1 in myelin-associate d globulin-positive oligodendrocytes was found in ipsilateral and contralat eral cortex, Next to the lesion iron accumulation occurred after day 3 and increased strongly toward day 14 at times when HO-1 and -2 had decreased, s uggesting that HO activity does not directly contribute to postlesional iro n deposition. (C) 2000 Academic Press.