Hippocampal injury during acute TMEV infection is associated with apoptotic markers. Higher magnification images of the same areas of CA1 analyzed in Figure 8. A, D, G, J, M, P: Oxidative damage assessed by anti-8-OHdG immunostaining (red). B, E, H, K, N, Q: Activated caspase-3 immunoreactivity (red). C, F, I, L, O, R: TUNEL staining to show DNA cleavage (green). A–C: The CA1 region of sham-infected animals shows no evidence of oxidative damage (A), activated caspase-3 (B), or TUNEL positivity (C) at 7 dpi. D–R: In contrast, mice infected with TMEV show a time-dependent increase in oxidized nucleotides, activated caspase-3, and DNA cleavage. The arrow in (M) indicates a typical anti-8-OHdG-positive pyramidal neuron. The arrowhead in (K) indicates a typical activated caspase-3-positive pyramidal neuron. The hand in (O) indicates a typical TUNEL-positive pyramidal neuron. The day of maximum caspase-3 activation (H or K) precedes the onset of maximum DNA cleavage (O and R), while the onset of oxidative damage (G) is contiguous with caspase-3 activation. Scale bar = 50 μm (in R and applies to all panels). These results are representative of at least five mice in each of three separate experiments. DAPI-labeled nuclei are blue in all panels.