Fig. 6

Long-term reconstitution of bone marrow cells transplanted from chronic TBI mice causes innate immune dysfunction and neurological decline in host mice. (A) Chimera paradigm is illustrated. Mice were allowed to reconstitute for 8 months following transplantation. WT naïve (non-irradiated) mice were sex- and age-matched to both chimera groups. (B) Body weight was monitored at 8 months after irradiation (IR). (C-F) A battery of neurobehavioral tests was performed to assess forelimb grip strength (C), time on rotarod (D), time immobility in the tail suspension test (E), and cognitive function in Y-maze test (F). (G-H) Blood donor cells (CD45.1, G) and leukocyte (CD45+, H) were counted using flow cytometry. (I) Percentages of bone marrow LSK + frequencies were detected. (J) Spleen Ly6G + neutrophils were examining using flow cytometry, showing reduced mean fluorescence intensity (MFI) of IL-1b + cells in TBI→WT mice compared to SH→WT animals. Light gray = fluorescence minus one (FMO) control. (K-M) Phagocytic engulfment of IgG-coated beads (K), latex beads (L), and pHrodo-labeled E.coli particles (M) were detected in spleen Ly6G + neutrophils. Left panels of K-M are representative dot plots. Data were analyzed using one-way ANOVA group analysis with Tukey’s test for multiple comparisons (B-I) or Student’s T-test for two group comparisons (J-M). n = 7 mice/group. ****P < 0.0001, **p < 0.01, *p < 0.05. SH: Sham