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Oxidative Stress after Subarachnoid Hemorrhage in gp91phox Knockout Mice

Published online by Cambridge University Press:  02 December 2014

Shimin Liu ,
Jiping Tang ,
Robert P Ostrowski ,
Elena Titova ,
Cara Monroe ,
Wanqiu Chen ,
Wendy Lo ,
Robert Martin  and
John H Zhang
Shimin Liu
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Jiping Tang
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Robert P Ostrowski
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Elena Titova
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Cara Monroe
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Wanqiu Chen
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Wendy Lo
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Robert Martin
Affiliation:
Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA
John H Zhang
Affiliation:
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA
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Abstract

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Background:

Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH.

Methods:

Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery.

Results:

Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice.

Conclusions:

Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.

Résumé:

RÉSUMÉ:

Le stress oxydatif après une hémorragie sous-arachnoïenne chez les souris knock-out gp91-phox.

Contexte:

Le stress oxydatif contribue de façon importante aux lésions précoces dues à une hémorragie sous-arachnoïenne (HSA). La NADPH oxydase est une des sources majeures de dérivés réactifs de l'oxygène qui est régulée à la hausse après une HSA. Nous avons émis l'hypothèse que le stress oxydatif induit par la NADPH oxydase est une cause majeure de dommage cérébral après une HSA. Méthodes : Nous avons étudié les dommages cérébraux précoces chez le modèle de HSA par perforation endovasculaire chez des souris de phénotype sauvage (ps) et des souris knock-out (ko) gp91-phox. Le taux de mortalité, l'?dème cérébral, le stress oxydatif et la production de superoxyde ont été mesurés 24 heures après l'HSA. L'évaluation neurologique était faite 23 heures après la chirurgie. Résultats : Le génotypage a confirmé l'existence d'un gène gp91-phox non fonctionnel chez les souris ko. On n'a pas constaté de différence dans la mesure du débit sanguin cérébral entre les souris ps et les souris ko en phase d'ischémie aiguë induite par l'HSA. L'HSA a causé une augmentation significative du contenu aqueux dans l'hémisphère ipsilatéral ainsi qu'une augmentation des niveaux de malondialdéhyde et de la production de superoxyde. Il n'y avait pas de différences significatives entre les groupes de souris ps et ko quant au taux de mortalité, au contenu aqueux du cerveau et à l'intensité du stress oxydatif post HSA. Conclusions : Nos résultats indiquent que gp91-phox ne joue pas un rôle critique dans les dommages cérébraux précoces après une HSA. Nous discutons d'un mécanisme compensatoire d'adaptation pour la production de radicaux libres chez les souris ko.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 3 , August 2007 , pp. 356 - 361
Copyright
Copyright © The Canadian Journal of Neurological 2007

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