Figure 6

From: Candesartan, an Angiotensin II AT1-Receptor Blocker and PPAR-γ Agonist, Reduces Lesion Volume and Improves Motor and Memory Function After Traumatic Brain Injury in Mice

Figure 6

The influence of PPARγ antagonist on the neuroprotective effects of candesartan following brain injury. Mice were administered vehicle, candesartan (CD) and/or the PPARγ antagonist, T0070907 by daily injection for 3 days, starting 5 h before injury. (a) Effects on PPARγ mRNA expression. PPARγ mRNA expression was not significantly altered after injury (CCI) and/or after CD treatment in the perilesional cortex as compared with vehicle-treated naive (NAI) mice at 3 dpi (mean±SEM, n=4). (b) Effects on lesion volume. At 3 dpi, CD significantly reduced the lesion volume (*p<0.05, CCI-VH vs CCI-CD). T0070907 administration alone (CCI-T0) or together with CD (CCI-CD+T0) did not alter the lesion volume compared with the vehicle group (NS, p>0.05), nor was it significantly different than in mice treated with CD alone (NS, p>0.05, CCI-VH vs CCI-CD+T0) (mean±SEM, n=7–8). (c) Effects on Iba-1-positive microglial cells. CD significantly reduced the number of Iba-1-positive cells in the injured cortex (***p<0.001, **p<0.005, CCI-VH vs CCI-CD). This effect was abolished by co-treatment with T0070907 (*p<0.05, CCI-CD vs CCI-CD+T0). Treatment with T0070907 alone (CCI-T0) did not change the number of Iba-1-positive cells (NS, p>0.05, CCIVH vs CCI-T0) (mean±SEM, n=4–7). (d) Effects on the ability of mice to remain on the rotarod. CCI significantly reduced the ability of mice to remain on the rotarod (++p<0.01, SHVH vs CCI-VH). CD treatment alone significantly enhanced the ability of CCI injured mice to remain on the rotarod at 1 dpi (*p<0.05, CCI-VH vs CCI-CD). The protective effect of CD at 1 dpi was no longer significant after co-administration of T0070907 (NS, p>0.05, CCI-VH vs CCI-CD-T0) (mean±SEM, n=7; data were analyzed by two-way ANOVA with Bonferroni post-tests). VH, vehicle; CD, candesartan; T0, T0070907; NS, not significant.