Fig. 5.

Eliminating cis P-tau in ssTBI mice with cis mAb prevents a range of pathological and functional outcomes during the chronic phase. Mice were subjected to long-term treatment regimens over 4-months, followed by a 2-month washout a and then underwent functional, biochemical, and pathological examinations. Orange arrows, ssTBI; black arrows, antibody injection; green lines, functional, or pathological assays. Cis mAb treatment of ssTBI mice for 4 months effectively eliminated cis P-tau induction and total tau accumulation b, c, and prevented the development of axonal pathology d and tau oligomerization e both in the cortex and hippocampus, as well as prevented sensorimotor coordination deficits, as detected by Ledge assay f and string suspension g and urinary incontinence as assayed by spontaneous urinary pattern i at 6 months after injury, with no deficit in novel object location recognition h. Microscope images correspond to the medial prefrontal cortex of sham (left), ssTBI + IgG (middle), and ssTBI + cis mAb (right) with quantification data in different brain regions being present at right panels. Inset images are the high magnification image of selected area denoted by the white. Scale bar, 40 μm. Axonal bulb also referred to as a retraction ball indicated with red arrow in Gallyas silver staining. mPFC, medial prefrontal cortex; HC, hippocampus; Thal, thalamus; BLA, basolateral amygdala. ND, not detectable; NS, not significant. Brains from 4−5 WT male mice were studied in immunohistochemistry, 5−6 mice underwent urinary pattern test and 9−10 WT mice underwent other behavioral studies per group. The data were presented as means ± SEM. The p-values were calculated using unpaired two-tailed parametric Student’s t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001