Fig. 9

Re-expression of OPG in neurons with nuclear calcium buffering reduces microgliosis and prevents synaptic degradation after TBI. A–C Buffering of nuclear calcium signaling significantly increased the density of IBA1 + /TMEM119 + , IBA1 + /CD11c + , IBA1 + /CST7 + and IBA1 + /CD169 + cells 24 h after TBI compared to TBI alone (CT vs PT; for IBA1 + /TMEM119 + 7.56 ± 0.48 vs 14.37 ± 1.74; for IBA1 + /CD11c + 6.74 ± 0.42 vs 11.70 ± 1.33; for IBA1 + /CST7 + 3.17 ± 0.29 vs 6.44 ± 1.05; for IBA1 + /CD169 + 1.38 ± 0.329 vs 9.56 ± 0.934). Re-expression of OPG decreased IBA1 + /TMEM119 + , IBA1 + /CD11c + , IBA1 + /CST7 + ; IBA1 + /CD169 cells compared to PV.NLS TBI (PT vs POT; for IBA1 + /TMEM119 + cells 14.37 ± 1.74 vs 8.02 ± 0.40; for IBA1 + /CD11c + cells 11.7 ± 1.33 vs 7.52 ± 0.21; for IBA1 + /CST7 + cells 6.44 ± 1.05 vs 2.20 ± 0.54; for IBA1 + /CD169 + 9.56 ± 0.93 vs 1.44 ± 1.38). Likewise, re-expression of OPG normalized the fraction of IBA1 + /CST7 + and IBA1 + /CD169 + compared to PV.NLS TBI (PT vs POT; for CST7 + 52.14 ± 4.91% vs 28.98 ± 6.44%; for CD169 + 68.01 ± 15.06% vs 20.67 ± 14.95%). N = 3. Mean ± SD Scale bar: 40 µm (overview) and 20 µm (insert). D, E Re-expression of OPG together with buffering of nuclear calcium signaling did not alter core synaptic density compared to PV.NLS-TBI but significantly increased the synaptic density in the perilesional area compared to PV.NLS-TBI (PT vs POT; 298.3 ± 78.1 vs 576.3 ± 66.8). N = 4. F OPG re-expression together with nuclear calcium buffering did not alter core neuronal density compared to TBI alone but significantly increased neuronal density in the perilesional areas (CT vs POT 25.13 ± 2.26 vs 32.01 ± 5.38). Yellow inserts show analyzed core and perilesional areas. Scale bar: 100 µm (overview) and 5 µm (insert). Data are shown as mean ± SD. N = 4. *p < 0.05; **p < 0.01; ***p < 0.001