Abstract
Purpose:
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Ocular and vision damage has been reported previously in humans and recently in several rodent studies employing either a blast injury animal model or a fluid percussion injury model. However, both animal models relate to injuries which occur relatively rarely within the spectrum of human TBI. A novel, closed head impact injury mouse model was recently developed at the Roskamp Institute to enable characterization of the consequences of repetitive mild TBI (r-mTBI). The purpose of this study was to study the effects of this model on the mouse visual system.
Methods:
Adult C57BL/6 mice (n = 8/group, 10 weeks of age) were randomly assigned to either r-mTBI or repetitive sham treatment (r-sham; anesthesia only) groups. Five consecutive hits with an inter-concussion interval of 48 hours were applied. Preliminary experiments demonstrated that there were no skull fractures, hemorrhages or cerebral contusions using this injury model. Mice were euthanized at 4 and 26 weeks and the eyes and optic nerves were examined histologically. Specifically, hematoxylin and eosin (H&E) staining was applied to the eye cross sections at 4 and 26 weeks and GFAP and Luxol Fast Blue (LFB) staining were applied to the optic nerve cross sections and corpus callosum at 26 weeks. At the same time point, optic nerve sections were stained also for Myelin Basic Protein (MBP).
Results:
H&E staining demonstrated cellular loss in the ganglion cell layer in the retina at 4 weeks and at 26 weeks. At 26 weeks LFB showed areas of reduced myelin content in the optic nerve cross-sections and in corpus callosum in r-mTBI mice, but not in r-sham mice. MBP staining confirmed this finding for the optic nerve. Similarly, GFAP expression was more marked in cross sections of optic nerves and corpus callosum from r-mTBI compared to sections from r-sham mice.
Conclusions:
To the best of our knowledge, this is the first observation of neuronal cell loss in the retinal ganglion cell layer and a myelin loss in the optic nerve and corpus callosum after closed head repetitive mTBI in the mouse. Ongoing studies continue the characterization of the model to further advance our understanding of the visual consequences of mTBI.
Keywords: 494 degenerations/dystrophies •
742 trauma •
629 optic nerve