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Sulforaphane pre‐treatment reduces blood‐brain barrier disruption in experimental stroke by inducing heme oxygenase‐1 expression in the glio‐vascular complex of the peri‐infarct region
Author(s) -
Alfieri Alessio,
Srivastava Salil,
Siow Richard,
Modo Michel,
Duchen Michael,
Fraser Paul,
Mann Giovanni
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.682.2
Subject(s) - heme oxygenase , penumbra , sulforaphane , blood–brain barrier , medicine , heme , stroke (engine) , chemistry , endothelium , pharmacology , ischemia , cancer research , central nervous system , enzyme , biochemistry , engineering , mechanical engineering
Heme oxygenase‐1 (HO‐1) serves as an inducible protective factor by its antioxidant and anti‐inflammatory actions. The isothiocyanate sulforapahane (SFN) induces HO‐1 via Nrf2. We have investigated HO‐1 induction in brain microvessels after experimental stroke, with and without SFN. Sprague‐Dawley rats (250–300g) were subjected to 70 min middle cerebral artery occlusion (MCAo) and 24 h reperfusion. SFN (5 mg/kg) was injected 1 h before MCAo. Brain sections were fluorescently stained for HO‐1 along with cell markers and IgG as marker of leak. HO‐1 expression was induced at 24h in microvessels of the peri‐infarct region, which was characterized by reduced leak compared to the infarct core. SFN reduced leakage into the brain (34±15% vs . 71±8% in untreated rats; P <0.05) and increased induction of HO‐1 in the penumbra (15±4% vs . 7±1%; P <0.05). HO‐1 upregulation was associated with perivascular astrocytes rather than the endothelium. Therefore, HO‐1 over‐expression in the glio‐vascular complex provides a protective mechanism against stroke, which can be targeted with SFN to prevent disruption of the blood‐brain barrier. Supported by the Henry Smith Charity and British Heart Foundation