Figure 6.

Reduction of LPS/HI brain damage in mice lacking CCR2 in monocytes. (A-C) Homozygous CCR2^RFP/^RFP mice contained significantly fewer RFP⁺ monocytes in 24 h post-LPS/HI brain than CCR2^RFP/⁺ mice (p < 0.05 by unpaired t-test, n = 6 for each). (D-F) LPS/HI injury significantly the brain IL-10 mRNAs, but elevated those for pro-inflammation (Tnf, Il1b and Il6), anti-inflammation (Arg1 and Chil3) and microglia activation (Ccl2, Nos2 and Tspo) mRNAs in CCR2^RFP/+ mice. These post-LPS/HI gene expression alterations were attenuated in CCR2^RFP/RFP mice. * p < 0.05, ** p < 0.01, *** p < 0.001 versus UN. N >4 for each group. (G-I) CCR2^RFP/RFP mice showed ~90% reduction of TUNEL⁺ cell death in the ipsilateral hippocampus than CCR2^RFP/+ mice at 1 d post-LPS/HI (p = 0.01 by unpaired t-test, n = 4 for each). (J-K) Representative images of CCR2^RFP/+ and CCR2^RFP/RFP mouse brains at 7 d post-LPS/HI injury. (L) CCR2^RFP/RFP showed significantly less tissue loss than CCR2^RFP/+ mice in the cerebral cortex (59.5 ± 4.6% vs 18.1 ± 5.0%) and hippocampus (57.4 ± 4.0% vs 20.4 ± 6.8%) at 7 d post-LPS/HI injury. N = 12 for CCR2^RFP/+ and n = 14 for CCR2^RFP/RFP mice. Asterisk indicates the ipsilateral hemisphere. Results are displayed as the mean ± SEM. Statistics are performed as unpaired t-test (C, I and L) and one-way ANOVA following by Tukey post-hoc analysis (D, E and F). Scale bar: 50 μm.