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Updated: Nov 6, 2025
Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion
Published on: April 19, 2024
Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic
Matthew I Hiskens1,2, Anthony G Schneiders1, Rebecca K Vella1
1School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, Queensland, Australia.
Abstract:
The cumulative effect of mild traumatic brain injuries (mTBI) can result in chronic neurological damage, however the molecular mechanisms underpinning this detriment require further investigation. A closed head weight drop model that replicates the biomechanics and head acceleration forces of human mTBI was used to provide an exploration of the acute and chronic outcomes following single and repeated impacts. Adult male C57BL/6J mice were randomly assigned into one of four impact groups (control; one, five and 15 impacts) which were delivered over 23 days. Outcomes were assessed 48 hours and 3 months following the final mTBI. Hippocampal spatial learning and memory assessment revealed impaired performance in the 15-impact group compared with control in the acute phase that persisted at chronic measurement. mRNA analyses were performed on brain tissue samples of the cortex and hippocampus using quantitative RT-PCR. Eight genes were assessed, namely MAPT, GFAP, AIF1, GRIA1, CCL11, TARDBP, TNF, and NEFL, with expression changes observed based on location and follow-up duration. The cortex and hippocampus showed vulnerability to insult, displaying upregulation of key excitotoxicity and inflammation genes. Serum samples showed no difference between groups for proteins phosphorylated tau and GFAP. These data suggest that the cumulative effect of the impacts was sufficient to induce mTBI pathophysiology and clinical features. The genes investigated in this study provide opportunity for further investigation of mTBI-related neuropathology and may provide targets in the development of therapies that help mitigate the effects of mTBI.
Insights
Repeated mild traumatic brain injuries (mTBI) cause chronic neurological damage, impairing spatial memory and altering gene expression in the brain. These findings highlight molecular targets for future mTBI therapies.
Area of Science:
- Neuroscience
- Neurology
- Molecular Biology
Background:
- Mild traumatic brain injury (mTBI) can lead to cumulative neurological damage.
- The molecular mechanisms behind mTBI-induced detriment require further elucidation.
Purpose of the Study:
- To investigate the acute and chronic outcomes of single and repeated mTBIs.
- To explore the molecular mechanisms underlying mTBI pathophysiology.
Main Methods:
- A closed head weight drop model was used in adult male mice.
- Mice received one, five, or 15 impacts over 23 days.
- Spatial learning and memory were assessed, alongside mRNA analysis of brain tissue and serum protein levels.
Main Results:
- Impaired spatial learning and memory were observed in the 15-impact group, persisting from acute to chronic phases.
- Upregulation of excitotoxicity and inflammation genes (MAPT, GFAP, AIF1, GRIA1, CCL11, TARDBP, TNF, NEFL) was noted in the cortex and hippocampus.
- No significant differences in serum phosphorylated tau or GFAP levels were found between groups.
Conclusions:
- Cumulative mTBI impacts are sufficient to induce mTBI pathophysiology and clinical features.
- Investigated genes offer potential targets for understanding mTBI neuropathology.
- These genes may serve as therapeutic targets for mitigating mTBI effects.
