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Updated: Mar 22, 2026
A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury
Published on: June 20, 2017
Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain
Radouil Tzekov1,2,3, Clint Dawson1, Megan Orlando1
1The Roskamp Institute, Sarasota, FL, United States of America.
Abstract:
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.
Insights
Repetitive mild traumatic brain injury (r-mTBI) causes optic nerve damage and retinal ganglion cell loss. Biochemical changes, including demyelination and altered proteins/lipids, were observed in mice three weeks post-injury.
Area of Science:
- Neuroscience
- Ophthalmology
- Traumatic Brain Injury Research
Background:
- Repetitive mild traumatic brain injury (r-mTBI) has known neuropathological and biochemical effects on the visual system.
- Understanding these effects is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the consequences of r-mTBI on the retina and optic nerve in a mouse model.
- To identify specific molecular and cellular changes associated with r-mTBI in the visual pathway.
Main Methods:
- Utilized a mouse model of r-mTBI, with a control group receiving repetitive sham anesthesia.
- Assessed retinal ganglion cell (RGC) number via histology and immunohistochemistry.
- Analyzed optic nerve tissue for cellularity, myelin content, and performed proteomic and lipidomic analyses at 3 weeks post-injury.
Main Results:
- r-mTBI mice showed increased optic nerve cellularity and demyelination compared to controls.
- A significant decrease (~25%) in Brn3a-positive RGCs was observed in r-mTBI mice.
- Proteomic and lipidomic analyses revealed alterations in proteins (e.g., neurofilaments, tubulin, heat shock proteins) and lipids (e.g., lysophosphatidylcholine) consistent with neuronal damage and demyelination.
Conclusions:
- r-mTBI induces significant neuropathological and biochemical changes in the optic nerve and retina.
- These findings correlate histological observations with molecular alterations, highlighting key affected pathways.
- The study provides a basis for identifying therapeutic targets to mitigate visual deficits following r-mTBI.
