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Alexandra Quezada, Megan Gautier, Benoit Mouzon, Joseph Ojo, Fiona Crawford, Radouil T Tzekov; Optic nerve changes after mild traumatic brain injury in mice expressing human Tau. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6229.
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A role for the tau protein in the pathogenesis of chronic traumatic encephalopathy and the consequences of repeated mild traumatic brain injury (r-mTBI) has received recent attention because of the evidence from high profile autopsy cases and the increased amount of significant health consequences of repetitive mTBI. However data from animal models are limited, and there are no data focusing on effects of tau on the visual system after TBI. Thus, the current study was designed to evaluate the long-term effects of r-mTBI on the visual system of mice expressing human tau protein.
Male mice expressing human tau protein on a null murine tau background (hTau, Jackson Laboratory, aged 3 months) were used. Single mTBI (s-mTBI; n= 4) was induced according to an established model. According to the same model, repetitive mild traumatic brain injury (r-mTBI; n =4) was induced by applying 5 impacts with an interinjury interval of 48 hours, while repetitive sham (r-sham; n = 3) received anesthesia of the same duration. Histological evaluation of the optic nerves was carried out at 12 months post injury. Naïve mice (n = 6; 6-9 mo old C57BL/6 retired breeders) served as control.
Slightly increased cellularity (~17%) and a slight disorganization of the nuclear arrangement was observed in optic nerves of mice after r-sham, s-mTBI and r-mTBI mice compared to the optic nerves of naive control mice. Surprisingly, there was no statistically significant difference in optic nerve cellularity between r-sham and s-mTBI or r-mTBI (p = 0.9779; Kruskal-Wallis test) or between any of these groups and naïve mice (p>0.05). Focal areas of demyelination were observed in some s-mTBI and r-mTBI optic nerves.
We have previously demonstrated increased cellularity in the optic nerve in wild type mice after TBI. Overall, the degenerative changes in the optic nerves after r-mTBI in hTau mice at 12 months post injury were milder compared to changes observed at a similar age (8 months) in wild type mice and, despite the localized myelin loss in some nerves, the overall level of cellularity was not different from naive mice or between the groups. Further characterization of this model currently underway could shed additional light on the apparent protective effect of human tau expression in r-mTBI.
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