Fig 6. Microglial Nr4a1 knockout promotes Tnf expression and exacerbates brain injury in experimental ischemic stroke.
(A–D) mRNA levels of several inflammatory factors in ischemic hemispheres from Tmem119-CreERT2; Nr4a1fl/fl mice and Nr4a1fl/fl mice 6 h and 24 h after MCAO (n = 3 for sham mice, n = 5 for MCAO mice per group). (E) Representative images of Nissl-stained tissues from Tmem119-CreERT2; Nr4a1fl/fl mice and Nr4a1fl/fl mice 3 days after MCAO. (F) Quantification of the infarct size, as measured by Nissl staining (n = 9 for Nr4a1fl/fl + Saline mice, n = 11 for Nr4a1fl/fl + ETA mice, n = 11 for Tmem119-CreERT2; Nr4a1fl/fl + Saline mice, n = 10 for Tmem119-CreERT2; Nr4a1fl/fl + ETA mice). (G–I) Neurological deficits were aggravated in Tmem119-CreERT2; Nr4a1fl/fl mice compared to Nr4a1fl/fl mice 1 day and 3 days after MCAO and rescued by ETA, as determined by the mNSS test (G) (n = 9 for Nr4a1fl/fl + Saline mice, n = 11 for Nr4a1fl/fl + ETA mice, n = 11–12 for Tmem119-CreERT2; Nr4a1fl/fl + Saline mice, n = 10 for Tmem119-CreERT2; Nr4a1fl/fl + ETA mice), foot fault test (H) (n = 9 for Nr4a1fl/fl + Saline mice, n = 11 for Nr4a1fl/fl + ETA mice, n = 10–12 for Tmem119-CreERT2; Nr4a1fl/fl + Saline mice, n = 9–10 for Tmem119-CreERT2; Nr4a1fl/fl + ETA mice) and grip strength test (I) (n = 9 for Nr4a1fl/fl + Saline mice, n = 11 for Nr4a1fl/fl + ETA mice, n = 11–12 for Tmem119-CreERT2; Nr4a1fl/fl + Saline mice, n = 10 for Tmem119-CreERT2; Nr4a1fl/fl + ETA mice). Data are presented as mean ± SEM. In (A–D), two-way ANOVA with post hoc Bonferroni’s test. In (F), one-way ANOVA with post hoc Bonferroni’s test. In (G–I), two-way ANOVA with post hoc Bonferroni’s test (day 3 after MCAO) *P < 0.05; **P < 0.01; ***P < 0.001. The underlying data for this figure can be found in S1 Data. MCAO, middle cerebral artery occlusion.