DOI: 10.1161/01.str.28.11.2252. Ischemic Stroke Injury Is Reduced in Mice Lacking a Functional NADPH Oxidase

Ischemic Stroke Injury Is Reduced in Mice Lacking a Functional NADPH Oxidase

10.1161/01.str.28.11.2252

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

Background and Purpose Free radicals account for a significant proportion of the brain damage that occurs during ischemic stroke. Using mutant mice (X-CGD) with a dysfunctional phagocytic NADPH oxidase, we investigated the role of this superoxide-generating enzyme as a mediator of the reperfusion injury in a mouse model of middle cerebral artery occlusion. Methods Transient (2 hour) middle cerebral artery occlusion was performed in X-CGD or wild-type litter mates (8- to 10-week-old). After 22 hours of reperfusion, brains were harvested and infarct volume delineated using 2,3,5-triphenyltetrazolium chloride. To elucidate the origin of the damaging NADPH oxidase, transient ischemia was also performed in X-CGD or wild-type mice transplanted with wild-type C57 Bl/6J or X-CGD bone marrow, respectively. Results The infarct volume induced by transient ischemia was significantly less in X-CGD mice (29.1±5.6 mm 3 ; n=13) than wild-type littermates (54.0±10.6 mm 3 ; n=10; P <.05). The elimination of a functional NADPH oxidase from either the circulation or the central nervous system, by performing the appropriate bone marrow transplant experiments, did not reduce the infarct size induced by transient ischemia. This suggests that in order to confer protection against transient ischemia and reperfusion, a putative neuronal and circulating NADPH oxidase need to be inactivated. Conclusions Brain injury was reduced in mice lacking a functional NADPH oxidase in both the central nervous system and peripheral leukocytes, suggesting a pivotal role for the NADPH oxidase in the pathogenesis of ischemia-reperfusion injury in the brain.

Bibliography

Walder, C. E., Green, S. P., Darbonne, W. C., Mathias, J., Rae, J., Dinauer, M. C., Curnutte, J. T., & Thomas, G. R. (1997). Ischemic Stroke Injury Is Reduced in Mice Lacking a Functional NADPH Oxidase. Stroke, 28(11), 2252â2258.

Authors 8

Claire E. Walder (first)
Simon P. Green (additional)
Walter C. Darbonne (additional)
Joanne Mathias (additional)
Julie Rae (additional)
Mary C. Dinauer (additional)
John T. Curnutte (additional)
G. Roger Thomas (additional)

References 40 Referenced 280

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Wei EP, Kontos HA. Oxygen radicals in cerebral ischemia. Physiologist. 1987;30:122-128. / Physiologist (1987)
10.1016/0891-5849(89)90057-9
Liu TH, Beckman HS, Freeman BA, Hogan EL, Hsu CY. Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury. Am J Physiol. 1989;256:H589–H593. / Am J Physiol (1989)
He YY, Hsu CY, Ezrin AM, Miller MS. Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion. Am J Physiol. 1993;265:H252–H256. / Am J Physiol (1993)
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Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 6:12 p.m.)
Indexed	1 week, 3 days ago (Aug. 21, 2025, 2:12 p.m.)
Issued	27 years, 10 months ago (Nov. 1, 1997)
Published	27 years, 10 months ago (Nov. 1, 1997)
Published Print	27 years, 10 months ago (Nov. 1, 1997)

Funders 0

None

BibTeX

@article{Walder_1997, title={Ischemic Stroke Injury Is Reduced in Mice Lacking a Functional NADPH Oxidase}, volume={28}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.28.11.2252}, DOI={10.1161/01.str.28.11.2252}, number={11}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Walder, Claire E. and Green, Simon P. and Darbonne, Walter C. and Mathias, Joanne and Rae, Julie and Dinauer, Mary C. and Curnutte, John T. and Thomas, G. Roger}, year={1997}, month=nov, pages={2252–2258} }

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