Astrocyte overexpression of heme oxygenase-1 improves outcome after intracerebral hemorrhage.

Autor:	Chen-Roetling J; From the Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (J.C.-R., C.S.R., R.F.R.); and Lady Davis Institute, Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada (W.S., H.M.S.)., Song W; From the Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (J.C.-R., C.S.R., R.F.R.); and Lady Davis Institute, Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada (W.S., H.M.S.)., Schipper HM; From the Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (J.C.-R., C.S.R., R.F.R.); and Lady Davis Institute, Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada (W.S., H.M.S.)., Regan CS; From the Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (J.C.-R., C.S.R., R.F.R.); and Lady Davis Institute, Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada (W.S., H.M.S.)., Regan RF; From the Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (J.C.-R., C.S.R., R.F.R.); and Lady Davis Institute, Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada (W.S., H.M.S.). Raymond.Regan@jefferson.edu.
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2015 Apr; Vol. 46 (4), pp. 1093-8. Date of Electronic Publication: 2015 Feb 17.
DOI:	10.1161/STROKEAHA.115.008686
Abstrakt:	Background and Purpose: Heme oxygenase-1 (HO-1) catalyzes the rate-limiting reaction of heme breakdown and may have both antioxidant and pro-oxidant effects. In previous studies, HO-1 overexpression protected astrocytes from heme-mediated injury in vitro. In the present study, we tested the hypothesis that selective astrocyte overexpression of HO-1 improves outcome after intracerebral hemorrhage. Methods: Male and female transgenic mice overexpressing human HO-1 driven by the GFAP promoter (GFAP.HMOX1) and wild-type controls received striatal injections of autologous blood (25 μL). Blood-brain barrier disruption was assessed by Evans blue assay and striatal cell viability by methylthiazolyldiphenyl-tetrazolium bromide assay. Neurological deficits were quantified by digital analysis of spontaneous cage activity, adhesive removal, and elevated body swing tests. Results: Mortality rate for wild-type mice was 34.8% and was similar for males and females; all GFAP.HMOX1 mice survived. Striatal Evans blue leakage at 24 hours was 23.4±3.2 ng in surviving wild-type mice, compared with 10.9±1.8 ng in transgenics. Perihematomal cell viability was reduced to 61±4% of contralateral at 3 days in wild-type mice, versus 80±4% in transgenics. Focal neurological deficits were significantly reduced and spontaneous cage activity was increased in GFAP.HMOX1 mice. Conclusions: Selective HO-1 overexpression in astrocytes reduces mortality, blood-brain barrier disruption, perihematomal cell injury, and neurological deficits in an autologous blood injection intracerebral hemorrhage model. Genetic or pharmacological therapies that acutely increase astrocyte HO-1 may be beneficial after intracerebral hemorrhage. (© 2015 American Heart Association, Inc.)
Databáze:	MEDLINE
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