INDUCTION OF HEME OXYGENASE-1 AFTER HYPEROSMOTIC OPENING OF THE BLOOD-BRAIN-BARRIER

The induction of the stress protein heme oxygenase-1 (HO-1) was studie d in the rat brain after intracarotid administration of hyperosmolar m annitol. HO-1 was immunolocalized in fixed sections of brain 24 h to 7 days after injection. Immunoglobulin G (IgG) was immunolocalized in a djacent sections to demonstrate areas of breakdown of the blood-brain barrier. Induction of HO-1 was also evaluated by Western immunoblots, performed at 24 h after the insult. Immunofluorescent double labelling with monoclonal antibodies to HO-1 and either glial fibrillary acidic protein or the complement C3bi receptor was used to determine if glia /macrophages expressed HO-1. There was pronounced, widespread inductio n of HO-1 in the ipsilateral hemisphere and cerebellum by 24 h both by immunocytochemistry and by Western blots. This induction was markedly attenuated at later times. HO-1 was induced in astrocytes and microgl ia/macrophages in the ipsilateral hemisphere. In addition, the protein was induced in Bergmann glia and scattered microglia/macrophages in t he cerebellum. The mechanism of induction of HO-1 in glia after openin g of the blood-brain barrier could include exposure to heme proteins, denatured proteins and other plasma constituents known to induce HO-1. This glial induction may reflect a protective response of these cells . (C) 1998 Elsevier Science B.V.