Optic nerve changes after repeated closed-head traumatic brain injury in wild type and htau mice

摘要

Purpose : We have reported previously effects on the visual system from a novel, closed-head impact injury mouse model at sub-chronic (3 weeks) and chronic (3 months) time points post mild TBI (mTBI) injury. The purpose of the current work is to extend these findings into acute time points (less than 3 weeks) post injury. Methods : Adult C57BL/6 mice (n = 5-7/group, 10 weeks of age) and htau mice (15 weeks of age, or 65 weeks of age, n=5-7/group) were assigned to either repeated mTBI (r-mTBI) or repetitive sham treatment (r-sham; anesthesia only) groups and five consecutive hits were applied according to an established protocol. Mice were euthanized at 24 hours after the last injury and optic nerves were examined histologically. Specifically, hematoxylin and eosin (H&E) staining was applied and the distribution of the nuclei within the nerve was assessed in three regions of 1,000 microns span along the length of the nerve. Myelin content was estimated with Luxol Fast Blue (LFB) staining and microglial activation with staining for Iba-1. Results : In all three groups, H&E staining demonstrated increased cellularity in the optic nerve at 24 hours post injury. However, the distribution of the increased cellularity along the length of the nerve was not uniform, but demonstrated a trend for a peak in the region closest to the chiasm in wild type and older htau mice (55.1 and 125.2% increase vs. r-sham, respectively), while it diminished in the second and third region further away from the chiasm (28.5 and 48.5% in second region; -8.6 and 24.1% in third region). In contrast, younger htau mice showed much less of a change in cellularity across the three regions (37.3%, 18.2%, 29.6%). In both young and old htau mice the difference in cellularity for the region closet to the chiasm was significant (p0.01, p0.001, respectively). In all three groups there was sings of incipient demyelination in the center of the nerve, associated with the areas of peak cellularity. Similarly, Iba-1 immunoreactivity was increased in all three groups. Conclusions : These data confirm the existence of a vulnerability region in the optic nerve at an acute time point after r-mTBI. This region coincides with a region of demyelination increased microglial activation and where a a??cavernousa?? type of optic nerve degeneration develops at ~3 months post injury. Ongoing studies continue the characterization of these changes at a molecular level. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.