Purpose Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase catalyzes the formation of reactive oxygen species (ROS) in many cell types, initially discovered in macrophages and monocytes. The ROS, in turn, cause inflammation, apoptosis, and necrosis. Of the five subunits that compose NADPH oxidase, the gp91 subunit has been shown to be the catalytic component of the enzyme. Studies have shown that when this component is blocked, cell damage is diminished. Blocking the gp91subunit in the setting of subarachnoid hemorrhage (SAH) may decrease neuronal cell death and therefore neurologic deficits. Therefore, we hypothesized that in the gp91phox knockout mice there would be less neurologic deficits, brain edema, and blood-brain barrier disruption.
Methods To test this theory, a double-blind study was conducted comparing the outcomes of C57BL/6 wild-type mice with gp91phox knockout mice using a SAH model. Mice were evaluated 23 hours post-SAH for neurologic deficits. At 24 hours, immunohistochemistry and nissl staining were performed.
Results Based on the limited animal numbers, no statistical difference was found in the neurologic scores, brain-water content, and cerebral blood flow between the wild-type and transgenic groups. However, statistical difference was seen in the mortality rates between transgenic and wild-type mice with a p value of .036. The higher mortality rate of 21.9% was present in the transgenic mice compared with a mortality rate of 3.1% for the wild type.
Conclusions The higher mortality rate observed in the transgenic mice may be due to up-regulation of alternate intracellular superoxide pathways. Further studies concerning the role of the up-regulation of superoxide generating pathways in gp91phox knockout mice will be conducted in the near future.
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