Fig. 1.

Severe TBI in humans due to motor vehicle accidents, assaults or falls induces prominent axonal injury and axonal cis P-tau induction in the cortex. a, b Severe TBI in humans induces early cis P-tau induction and axonal injury in the cortex. Whereas neither cis nor trans P-tau nor axonal injury was detected in normal brains or 1 h after TBI due to motor vehicle accident, robust cis P-tau and axonal injury, but not trans P-tau were detected in the cortex, but not in the hippocampus, as early as 8 h after motor vehicle accident, as detected by double IF, followed by isotype-specific secondary antibodies a or Gallyas silver staining b. Microscope images correspond to the cortex and hippocampus of control and TBI patients. TBI cases due to falls and assaults are shown in Supplementary Fig. 1. The number of TBI patients is 14. White arrows point to cis P-tau localization to axons; Red arrows point to axonal bulb. White scale bars, 20 µm and black scale bars, 40 µm. c, d cis P-tau (red) is diffusely co-localized (white arrows) with the axon marker tau (green) c, but not the dendrite marker MAP2 (green) d in human TBI cortex, with little cis in control, as detected by double IF, followed by confocal microscopy. e−h Cis P-tau is robustly induced after TBI in the absence of tau oligomers or tangles. Cortical sections of severe human TBI due to motor vehicle accidents were doubly immunostained with cis mAb (red) and T22 (tau oligomers) e, g or AT100 (tau tangles) f, h, followed by confocal microscopy. Normal controls as well as CTE and AD brains were used as negative and positive controls, respectively. Of note, cis mAb partially co-localized with T22 or AT100 in CTE or AD brains, but not in acute TBI brains