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Gaurav Kiri, Connie Miranda, April Myers, Fiona Crawford, Radouil T Tzekov; Increased Cellularity in the Optic Nerves of Mice after Repeated Traumatic Brain Injury. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5513.
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To assess long-term changes in cellularity of optic nerves in transgenic hTau mice that have undergone repetitive mild traumatic brain injury (r-mTBI) compared to repetitive-sham (r-sham) control groups.
Adult hTau mice (n=68; both genders) were assigned to either r-mTBI or r-sham control groups and a repeated injury (5 hits in 10 days) was performed according to an established protocol. Optic nerves were extracted at different time intervals post-injury (24 hours, 1 week, 2 weeks, 3, 6, and 12 months) and optic nerve tissue was stained with H&E. Nuclei cell counting was performed with the help of ImageJ software. Equivalent rectangular areas along the length of the optic nerves starting from the chiasm and progressing towards the eye were generated without overlap. Each optic nerve was divided into 3 areas of 1000 micrometers length each and cell density was calculated for each area. Additionally, optic nerves from the same animals were stained with DAPI, imaged, and cell nuclei were counted.
A statistically significant increase in total cell density of r-mTBI mice compared to r-sham mice was found at 24 hours (52.5-66.1%; p<0.001, t-test) and 2 weeks (58.6-73.7%; p<0.05) post-injury in all areas. Additionally, significant increases (48.9-67.4%; p<0.05) were found at 3,6 and 12 months for the area closest to the chiasm and at 3 and 6 months at the next, more distant area (39.6%, 25.7%; p<0.05). Estimates of cellularity based on DAPI staining yielded similar results as the one based on H&E.
These results confirm and strengthen our previous observations of increased cellularity in the optic nerve post-injury and extend it beyond 3 months. This supports the notion that an ongoing process of degeneration and local inflammation occurs in the optic nerve for prolonged periods of time and likely for the life-span of the animal post repeated TBI. Further characterization of chronic changes in the optic nerves after r-mTBI would be helpful in expanding our understanding of the effects of injury on the visual system.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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