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Attenuation of oxidative injury after induction of experimental intracerebral hemorrhage in heme oxygenase–2 knockout mice

Yan Qu Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennyslvania

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 M.D., Ph.D.
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Jing Chen-Roetling Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennyslvania

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 Ph.D.
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Luna Benvenisti-Zarom Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennyslvania

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Raymond F. Regan Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennyslvania

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 M.D.
Page Range:
428–435
Volume/Issue:
Volume 106: Issue 3
DOI link:
https://doi.org/10.3171/jns.2007.106.3.428
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Experimental evidence suggests that hemoglobin degradation products contribute to cellular injury after intracerebal hemorrhage (ICH). Hemoglobin breakdown is catalyzed in part by the heme oxygenase (HO) enzymes. In the present study, the authors tested the hypothesis that HO-2 gene deletion is cytoprotective in an experimental ICH model.

Methods

After anesthesia was induced with isoflurane, 3- to 6-month-old HO-2 knockout and wild-type mice were stereotactically injected with 15 μl autologous blood and a group of control mice were injected with an equal volume of sterile saline. Striatal protein and lipid oxidation were quantified 72 hours later using carbonyl and malondialdehyde assays. Cell viability was determined by performing a 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. Following blood injection, the investigators found a 3.4-fold increase in protein carbonylation compared with that in the contralateral striatum in wild-type mice; in knockout mice, the investigators found a twofold increase. The mean malondialdehyde concentration in injected striata was increased twofold in wild-type mice at this time, compared with 1.5-fold in knockout mice. Cell viability, as determined by MTT reduction, was reduced in injected striata to 38 ± 4% of that in the contralateral striata in wild-type mice, compared with 66 ± 5% in HO-2 knockout mice. Baseline striatal HO-1 protein expression was similar in wild-type and HO-2 knockout mice, but was induced more rapidly in the former after blood injection.

Conclusions

Deletion of HO-2 attenuates oxidative cell injury after whole-blood injection into the mouse striatum. Therapies that specifically target HO-2 may improve outcome after ICH.

Abbreviations used in this paper:

CNS = central nervous system ; DNP = 2,4-dintrophenylhydrazone ; HO = heme oxygenase ; ICH = intracerebral hemorrhage ; MTT = 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide ; PCR = polymerase chain reaction .
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Contributor Notes

Address reprint requests to: Raymond F. Regan, M.D., Department of Emergency Medicine, Thomas Jefferson University, 1020 Sansom Street, Thompson Building, Room 239, Philadelphia, Pennsylvania 19107. email: Raymond.Regan@jefferson.edu.
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