Figure 4

Brain injury is associated with bone marrow aplasia. (a) Evidence for loss of red marrow was apparent in several femurs collected from humanized mice 7 days after injury. Arrow indicates clearance of marrow in femur from vehicle control. (b) Graph represents quantification of mice with signs of bone marrow clearance from 8–9 mice per group (Chi-square test, *p = 0.03). (c) Histopathological examination revealed diffuse aggregates of histiocytes within the marrow of several animals, visible as eosinophilic areas among densely packed nucleated cells. Representative photomicrographs of femurs from each treatment group are shown. (d) Examples of necrosis, histiocytosis, and hemosiderin (brown iron deposits) are displayed. (e) Histopathological scores were based upon an ordinal numeric scoring system wherein 0 represented no abnormality and 4 displayed severe signs of pathology. NSG groups included 8–9 mice per treatment, and C57BL/6 mice included 9 mice per group. Red points represent mice scored as having loss of red marrow by gross observation. (f) Frequency of hCD3⁺ T cells in the bone marrow correlated with red marrow destruction (Mann–Whitney rank sum test, ***p < 0.001). Frequencies of hCD33⁺ myeloid or hCD19⁺ B cells were low in the bone marrow of mice with red marrow loss in one or both femurs as determined by gross observation (Mann–Whitney rank sum test, **p < 0.003). A total of 34 mice were included in these analyses and are plotted as individual points, along with mean and SEM.