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Induction of heme oxygenase-1 after hyperosmotic opening of the blood-brain barrier
Authors:Jeremy D Richmon  Kazumasa Fukuda  Nino Maida  Motoki Sato  Marcelle Bergeron  Frank R Sharp  SScott Panter  LJ Noble
Institution:aDepartment of Neurosurgery, University of California, San Francisco, CA, USA;bDepartment of Neurology, University of California, San Francisco, CA, USA;cSan Francisco General Hospital, San Francisco, CA, USA;dVeterans Affairs Medical Center, San Francisco, CA, USA
Abstract:The induction of the stress protein heme oxygenase-1 (HO-1) was studied in the rat brain after intracarotid administration of hyperosmolar mannitol. HO-1 was immunolocalized in fixed sections of brain 24 h to 7 days after injection. Immunoglobulin G (IgG) was immunolocalized in adjacent 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 induction 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 microglia/macrophages in the ipsilateral hemisphere. In addition, the protein was induced in Bergmann glia and scattered microglia/macrophages in the cerebellum. The mechanism of induction of HO-1 in glia after opening 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.
Keywords:Astrocyte  Bergmann glia  Heat shock protein  Macrophage  Mannitol  Microglia
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