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Updated: Nov 29, 2025
Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion
Published on: April 19, 2024
Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network
Xuan Niu1,2,3, Lijun Bai4, Yingxiang Sun2
1Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Background:
Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up.
Methods:
Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7 days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up (T-2). Forty-two matched healthy controls completed the same protocol at T-1 once.
Results:
At baseline, mTBI patients with APTH presented significantly increased GM volume mainly in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC), of which the dPCC volume can predict much worse impact of headache on patients' lives by HIT-6 (β = 0.389, P = 0.007) in acute stage. Serum levels of C-C motif chemokine ligand 2 (CCL2) were also elevated in these patients, and its effect on the impact of headache on quality of life was partially mediated by the dPCC volume (mean [SE] indirect effect, 0.088 [0.0462], 95% CI, 0.01-0.164). Longitudinal analysis showed that the dACC and dPCC volumes as well as CCL2 levels had persistently increased in patients developing CPTH 3 months postinjury.
Conclusion:
The findings suggested that structural remodelling of DMN brain regions were involved in the progression from acute to chronic PTH following mTBI, which also mediated the effect of inflammation processes on pain modulation.
Trial Registration:
ClinicalTrial.gov ID: NCT02868684 ; registered 16 August 2016.
Insights
Mild traumatic brain injury can lead to chronic posttraumatic headache. Inflammation and brain changes in specific regions like the dACC and dPCC are linked to headache progression after mTBI.
Area of Science:
- Neuroscience
- Neuroimaging
- Inflammation Research
Background:
- Mild traumatic brain injury (mTBI) frequently results in chronic posttraumatic headache (CPTH), affecting over 50% of patients.
- The neural mechanisms underlying CPTH development remain poorly understood.
- Investigating acute posttraumatic headache (APTH) may reveal pathways to CPTH.
Purpose of the Study:
- To investigate inflammation levels and cortical volume changes in acute posttraumatic headache (APTH) patients.
- To identify predictors of developing chronic posttraumatic headache (CPTH) at follow-up.
- To explore the relationship between inflammation, brain structure, and headache severity.
Main Methods:
- Seventy-seven mTBI patients underwent neuropsychological tests, serum cytokine analysis, and MRI scans within 7 days (T-1).
- Fifty-four patients completed follow-up assessments at 3 months (T-2).
- Forty-two healthy controls were included for baseline comparison.
Main Results:
- mTBI patients with APTH showed increased gray matter (GM) volume in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC).
- dPCC volume at baseline predicted greater headache impact (HIT-6 score).
- Elevated serum C-C motif chemokine ligand 2 (CCL2) levels were observed, partially mediated by dPCC volume in relation to headache impact. Persistent increases in dACC/dPCC volumes and CCL2 levels were noted in patients who developed CPTH.
Conclusions:
- Structural remodeling in Default Mode Network (DMN) brain regions is implicated in the progression from APTH to CPTH after mTBI.
- Inflammation processes, specifically elevated CCL2, contribute to pain modulation and are linked to structural brain changes.
- These findings highlight potential biomarkers and therapeutic targets for preventing chronic headache after mild TBI.
