Fig. 1

Patterns and evolution of p-Tau accumulation after closed head repetitive traumatic brain injury (rTBI). (a) Approximate location of the impact center over the intact mouse skull (blue circle) relative to the brain sections sampled for histological analysis (s1-s3; dashed lines). (b) Approximate location of p-Tau positive cells at 4 weeks after rTBI (composite of 8 mice; each red dot represents 8 p-Tau positive cells, blue ellipses indicate the spatial relation between the impactor and brain surface). Black boxes indicate the location of photomicrographs shown in panel c-e (box 1) and f–h (box 2). (c) Intact cerebral cortex without p-Tau accumulation at 1 week after rTBI. Progressive accumulation of p-Tau in the superficial layers of the cerebral cortex at (d) 4 weeks and (e) 24 weeks after rTBI. P-Tau accumulation in the corpus callosum at (f) 1 week, (g) 4 weeks, and (h) 24 weeks after rTBI (red asterisks). (f) In contrast to later time points, AT8-immunoreactivity at 1 week was restricted to dot-like staining in a subset of cells (arrowheads). Examples of p-Tau accumulation in (i) perivascular, (j) subpial, (k, l) periventricular, and (l) mammillary body locations as well as (m) at the depth of the superficial longitudinal fissure (white arrowheads) in perivascular (black arrowheads) and subpial (red arrowheads) locations at 4 weeks after rTBI. Scale bars are 30 µm (in c–j), 1 mm (k), and 300 µm (in l–m)