Figure 7.
Suppression of mitophagy worsens TBI-induced neuronal injury and behavioral deficits. A, B, Mdivi-1 did not affect general autophagosome biogenesis induced by CCI at 1 h post-injury (n = 3; mean ± SD; F(3,8) = 22.742; *p < 0.05 vs control and p > 0.05 CCI vs CCI+Mdivi-1 by one-way ANOVA and Tukey's post hoc test). A, C, The loss of mitochondrial proteins induced by CCI was partly reversed by mdivi-1. GAPDH was used as the loading control (n = 3; mean ± SD; F(3,8) = 12.583; *p < 0.05 vs control and #p < 0.05 vs CCI by one-way ANOVA and Tukey's post hoc test). D, E, Apoptotic cell death was assessed by TUNEL staining from five random fields in the injured cortex (n = 5; mean ± SD; F(5,24) = 40.362; #p < 0.05 vs CCI, 1 h by t test). Scale bar, 100 μm. F, 3-MA or mdivi-1 increased the level of cleaved-caspase-3 after CCI. G, Analysis of cortical lesion volume 7 d after TBI in Sprague-Dawley rats (n = 5; mean ± SD; F(2,15) = 4.163; *p < 0.05 vs CCI+V by one-way ANOVA and Tukey's post hoc test). H, Time spent (seconds) on the balance beam apparatus before and after CCI or sham (n = 8–12; mean ± SD; F(5,300) = 54.362; *p < 0.05 vs CCI + Vehicle by one-way ANOVA and Tukey's post hoc test). I, Latency (seconds) till rats locate a hidden (submerged) and visible platform on post-TBI Days 11–15 (n = 8–12; mean ± SD; F(5,300) = 72.128; *p < 0.05 vs CCI+Vehicle by one-way ANOVA and Tukey's post hoc test). J, NOR task performance 19 d after sham or CCI injury (n = 8–12 per group; mean ± SEM; F(5,36) = 9.714; *p < 0.05 vs CCI+Vehicle by one-way ANOVA and Tukey's post hoc test). V, Vehicle.