FIG. 1.

Characterization of the progression of pathology in the corpus callosum in a repetitive mild traumatic brain injury (r-mTBI) model. (A and B) Post-surgical data for r-mTBI. Apnea was not detected (nd) in r-sham mice (A), but was significantly increased after the first and the second impact in r-mTBI mice (A). The righting time is significantly delayed in r-mTBI versus r-sham mice (B). (C–E) Immunohistochemistry for β-APP is present mainly in neuronal cell bodies in r-sham mice (C). β-APP accumulations are readily detected in damaged axons (arrows) in r-mTBI mice acutely (D), but less marked by 7 days post-injury (E). (F–H) Immunohistochemistry for CD11b identifies microglia, which exhibit a resting phenotype in r-sham mice (F) with progressive activation evident at 24 h (G) and 7 days (H). (I–K) Immunohistochemistry for GFAP identifies astrocytes that have normal morphology in r-sham mice (I) and increasing cells with a reactive phenotype in r-mTBI mice between 24 h (J) and 7 days (K). (L–O) Quantification of immunohistochemistry in the corpus callosum. Axonal profiles with β-APP accumulations were increased very early after r-mTBI mice (L). Astrogliosis increases over the first week after r-mTBI (M). Microglial activation also increases significantly over the first week based on area of CD11b immunoreactivity (N) and an earlier reaction is detected by counting activated cells, which have intense CD11b and shorter, thicker processes (O). Dashed lines outline the corpus callosum. Values are mean ± standard error of the mean; n = 30 for post-surgical data; n = 5 per condition for histology data; scale bar (E), (H), and (K) = 50 μm; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. β-APP, beta amyloid precursor protein; GFAP, glial fibrillary acidic protein; r-sham, repetitive sham.