1. Loss of Nrf2 function in vivo increased cortical damage after permanent focal ischemia.
Loss of Nrf2 function in vivo increased cortical damage after permanent focal ischemia. Male mice (10-16 weeks of age) of various Nrf2 genotypes were subjected to permanent focal ischemia by cauterization of the distal middle cerebral artery, producing an infarct restricted to the cortex. Twenty-four hours or 7 d after stroke onset, mice were killed for evaluation of infarct size using cresyl violet staining. A, Representative examples for each genotype are shown from the 7 d survival group (infarct borders are demarcated by black line). B, To ensure that all genotypes received complete occlusion of regional cerebral blood flow, surgeries were guided by laser Doppler continuous measurements of blood flow through the skull above the temporal ridge. No difference in blood flow reduction was observed between the genotypes. C, E, A separate group of animals, killed 24 h after stroke, showed no significant differences in cortical damage between genotypes (visualized with TTC; data not shown). D, E, However, 7 d after stroke, Nrf2-/- mice sustained considerably more damage, which usually extended to medial and dorsal cortical regions, whereas Nrf2+/+ and Nrf2+/- controls exhibited no increase in infarct size beyond the 24 h time point. Data represent the mean ± SEM collected from n = 9, 3, and 8 mice for Nrf2+/+, Nrf2+/-, and Nrf2-/- groups, respectively (7 d survival). n = 8 and 5 mice for Nrf2+/+ and Nrf2-/- groups, respectively (24 h survival). *p < 0.05, **p < 0.01, and ***p < 0.001; paired two-tailed t test or one-way ANOVA with Bonferroni's post hoc test.
Andy Y. Shih et al. J. Neurosci. 2005;25:
©2005 by Society for Neuroscience