Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury

Glutathione peroxidase is an antioxidant enzyme that is involved in the con trol of cellular oxidative state. Recently, unregulated oxidative state has been implicated as detrimental to neural cell viability and involved in bo th acute and chronic neurodegeneration. In this study we have addressed the importance of a functional glutathione peroxidase in a mouse ischemia/repe rfusion model. Two hours of focal cerebral ischemia followed by 24 h of rep erfusion was induced via the intraluminal suture method. Infarct volume was increased three-fold in the glutathione peroxidase-1 (Gpx-1) -/- mouse com pared with the wild-type mouse; this was mirrored by an increase in the lev el of apoptosis found at 24 h in the Gpx-1 -/- mouse compared with the wild -type mouse. Neuronal deficit scores correlated to the histologic data. We also found that activated caspase-3 expression is present at an earlier tim e point in the Gpx-1 -/- mice when compared with the wild-type mice, which suggests an enhanced susceptibility to apoptosis in the Gpx-1 -/- mouse. Th is is the first known report of such a dramatic increase, both temporally a nd in level of apoptosis in a mouse stroke model. Our results suggest that Gpx-1 plays an important regulatory role in the protection of neural cells in response to the extreme oxidative stress that is released during ischemi a/reperfusion injury.