The consequences of oxidative stress were examined by DNA oxidation and lipid peroxidation. Immunostaining with anti-8-hydroxy-2′-deoxyguanosine (8-OH-dG) (Figure 3A) and anti-4- Hydroxy-2-nonenal (4-HNE) (Figure 3B), which are markers for DNA oxidative damage and lipid peroxidation, respectively, revealed significantly increased immunoreactivity of 8-OH-dG and 4-HNE in the cortex of 8-week-old KO mice after PWSI compared with age-matched fGluN1 controls. Interestingly, cortical PV interneurons in PWSI-exposed KO animals showed prominent staining with anti-8-OH-dG (Figure 3A) and anti-4-HNE (Figure 3B), suggesting that PV interneurons in KO animals are highly vulnerable to oxidative stress. Moreover, consistent with non-specific staining of DHE (Figure S1C in Supplement 1), weak 8-OH-dG and 4-HNE immunostaining was present in non-PV neurons in the KO animals after PWSI, presumably in the excitatory neurons.
