Repetitive Mild Traumatic Brain Injuries in Mice during Adolescence Cause Sexually Dimorphic Behavioral Deficits and Neuroinflammatory Dynamics
Bibliographic record
Abstract
Adolescent brain injuries have devastating impacts on lifelong health given that adolescence is a critical period for brain development. Adolescents are susceptible to mild traumatic brain injuries (mTBIs) acquired from collisions in contact sports, which are often sustained in a repetitive nature (repetitive mild traumatic brain injuries; RmTBIs), and cause compounding, sexually dimorphic neurological deficits. Neuroinflammation accompanies RmTBIs and may be a central driving force for chronic neurological decline. To date, the impact of neuroinflammation and sex-specific dynamics during adolescent RmTBIs has been understudied. A lateral impact model (LIM) was developed that mimics the biomechanical forces commonly experienced in human mTBIs. Here, we report novel sexually dimorphic neurobehavioral and -inflammatory responses using LIM to model adolescent RmTBIs. We first subjected adolescent male C57Bl/6 mice to one, three, or five RmTBIs at 24-h intervals and quantified neurobehavioral deficits, and brain volumetric and structural changes by magnetic resonance imaging. Five RmTBIs caused significant motor deficits, increased brain volume in cortex, hippocampus, and corpus callosum, and reduced white matter integrity in the corpus callosum. We then compared neurobehavioral deficits in adolescent male and female mice and observed sex-specific deficits in motor function, whereas both sexes had dysfunction in learning and memory. Flow cytometric quantification of neuroinflammatory responses revealed time- and sex-dependent infiltration of peripheral macrophages and T cells and male-specific decreases in microglia number. Using immunohistochemistry, we report specific microglia density decreases in male mice in the motor cortex and thalamus. We show novel neuroinflammatory responses after adolescent brain injuries that expands the current understanding of RmTBI pathophysiology in this critical neurodevelopmental period.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".