Fig. 5
From: Bi-directional neuro-immune dysfunction after chronic experimental brain injury
Short-term reconstitution of bone marrow cells transplanted from chronic TBI mice affect host neurological function and neuroinflammatory signaling. (A) Chimera paradigm is illustrated. WT naïve (non-irradiated) mice were sex- and age-matched to both chimera groups. Mice were allowed to reconstitute for 8 weeks following transplantation. n = 11–16 mice/group. (B) Body weight of animal was monitored before and at 4 and 8 weeks (wks) after irradiation (IR). (C-F) Graphs showed parameters (body speed, stride length, swing speed, and swing durations) of CatWalk gait analysis tested at 8 weeks after IR. (G-J) Locomotor function and depressive-like behavior were assessed in the accelerating rotarod (G), Grip strength (H), and Open field (I), and tail suspension (J) tests. (K) Short-term spatial working memory was evaluated in Y-maze test. (L-N) Plasma cytokine levels were examined using multiplex Enzyme-Linked Immunosorbent Assay (ELISA). The pro-aging/neurodegenerative cytokines IP-10, CCL11, and KC were significantly increased in TBI→WT mice compared to controls. n = 10–13 mice/group. (O-Q) Brain microglia and CD45hi leukocytes were detected using flow cytometry. A representative dot plot of leukocyte populations in the brain is illustrated in O. Quantification of CD45intCD11b+ microglia (P) and CD45hiCD11b+ myeloid cells (Q) are shown. (R-V) The transcriptomic profile of brain tissue at 8 weeks after IR was assessed using the NanoString nCounter Neuroinflammation panel. n = 4 mice/group. The Partial least squares-discriminant analysis (PLSDA) is illustrated (R). Heatmap of genes that are associated with Microglial Function (S), Inflammatory Signaling (T), and the Innate Immune Response (U) are shown. Color coding was based on Average Transcription Counts (normalized by housekeeping genes). Volcano plot analysis is indicated (V). Data were analyzed using one-way ANOVA group analysis with Tukey’s test for multiple comparisons. W: WT Naive; S: SH→WT; T: TBI→WT. ****P < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05. SH: Sham