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Radouil T Tzekov, Megan Gautier, Benoit Mouzon, Joseph Ojo, Davida Biggins, Fiona Crawford; Retinal ganglion cell loss and optic nerve changes in mice at two weeks and eight months post repeated traumatic brain injury. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3842.
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Preliminary data on the effects on the visual system from a novel, closed-head injury mouse model developed in the Roskamp Institute were reported in 2013 (IOVS, 54: E-Abstract 1427). The current work was designed to explore and characterize the effects of repeated mild traumatic brain injury (r-mTBI) on different time points with an emphasis on pathological changes in the optic nerve.
Adult male C57BL/6 mice (10-12 weeks old) were subjected to either r-mTBI (n =7) or repetitive sham (r-sham; n = 7), according to an established protocol. Mice were sacrificed and optic nerves extracted and processed for paraffin embedding at 2 weeks and 8 months post injury. Cellularity of the optic nerve and myelination was estimated after staining with H&E and Luxol Fast Blue. Mean optic nerve diameter was measured and compared between the two groups at 8 months. Optic nerves from naïve mice (n = 6; 6-9 month old C57BL/6 retired breeders) served as an additional control. In addition, retinal wholemounts were prepared and the total number of Brn-3a positive retina ganglion cells (RGCs) counts and distribution was done at 8 months.
Regions of focal demyelination were observed in the optic nerves after r-mTBI compared to r-sham or naive mice at 2 weeks and 8 months. In parallel, increased cellularity in r-mTBI optic nerves was observed at 2 weeks (a 25% increase) and at 8 months (a 107% increase). Average optic nerve diameter was decreased at 8 months (249 vs. 342 microns, a 27% decrease) in r-mTBI vs. r-sham. Reduction in the total number of RGCs was observed after r-mTBI at 8 months: 5,693 ± 2,848 vs. 34,231 ± 4,572, a significant (p<0.001) 76.5% decrease compared to r-sham and published control data.
Decrease in mean diameter, increased cellularity and regional loss of myelination of the optic nerve at subchronic and chronic time points post r-mTBI are indicative of an ongoing inflammatory and neurodegenerative process. The severity of this process is reflected by parallel changes in the retina demonstrated by the associated dramatic RGC loss at the chronic time point. Ongoing studies continue the characterization of the model at additional acute, subchronic and chronic time points.
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