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Updated: Jan 6, 2026
Development of an Uncomplicated Mild Traumatic Brain Injury Model Modified by Weight-Drop Method and Evidenced by Magnetic Resonance Imaging
Published on: April 11, 2025
Repeated mild traumatic brain injuries induce persistent changes in plasma protein and magnetic resonance imaging
David K Wright1,2, Rhys D Brady1,3, Alaa Kamnaksh4
1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
Abstract:
A single mild traumatic brain injury (mTBI) typically causes only transient symptoms, but repeated mTBI (RmTBI) is associated with cumulative and chronic neurological abnormalities. Clinical management of mTBI is challenging due to the heterogeneous, subjective and transient nature of symptoms, and thus would be aided by objective biomarkers. Promising biomarkers including advanced magnetic resonance imaging (MRI) and plasma levels of select proteins were examined here in a rat model of RmTBI. Rats received either two mild fluid percussion or sham injuries administered five days apart. Rats underwent MRI and behavioral testing 1, 3, 5, 7, and 30 days after the second injury and blood samples were collected on days 1, 7, and 30. Structural and diffusion-weighted MRI revealed that RmTBI rats had abnormalities in the cortex and corpus callosum. Proteomic analysis of plasma found that RmTBI rats had abnormalities in markers indicating axonal and vascular injury, metabolic and mitochondrial dysfunction, and glial reactivity. These changes occurred in the presence of ongoing cognitive and sensorimotor deficits in the RmTBI rats. Our findings demonstrate that RmTBI can result in chronic neurological abnormalities, provide insight into potential contributing pathophysiological mechanisms, and supports the use of MRI and plasma protein measures as RmTBI biomarkers.
Insights
Repeated mild traumatic brain injury (RmTBI) in rats caused lasting brain abnormalities and cognitive deficits. Advanced MRI and plasma protein analysis show promise as objective biomarkers for RmTBI diagnosis.
Area of Science:
- Neuroscience
- Biomarkers
- Traumatic Brain Injury Research
Background:
- Single mild traumatic brain injury (mTBI) often results in temporary symptoms.
- Repeated mild traumatic brain injury (RmTBI) is linked to persistent neurological issues.
- Objective biomarkers are needed for effective mTBI clinical management due to symptom variability.
Purpose of the Study:
- To investigate the chronic neurological effects of RmTBI in a rat model.
- To evaluate advanced magnetic resonance imaging (MRI) and plasma protein levels as potential RmTBI biomarkers.
- To explore the pathophysiological mechanisms underlying RmTBI-induced abnormalities.
Main Methods:
- Rats received two mild fluid percussion injuries or sham procedures five days apart.
- Structural and diffusion-weighted MRI, behavioral tests, and plasma proteomic analysis were performed.
- Measurements were taken at multiple time points post-injury (days 1, 3, 5, 7, and 30).
Main Results:
- RmTBI rats exhibited structural and diffusion abnormalities in the cortex and corpus callosum via MRI.
- Plasma proteomic analysis revealed markers of axonal/vascular injury, metabolic dysfunction, and glial reactivity in RmTBI rats.
- RmTBI rats displayed persistent cognitive and sensorimotor deficits.
Conclusions:
- RmTBI can lead to chronic neurological deficits and abnormalities.
- MRI and plasma protein biomarkers show potential for detecting RmTBI.
- Findings offer insights into RmTBI's underlying pathophysiological mechanisms.
