Chimera traumatic brain injury induces tauopathy in the RTG4510 mice
Bibliographic record
Abstract
Abstract Background Traumatic brain injury (TBI) is a major cause of death and disabilities in developed countries. We have previously designed an animal TBI model called Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). CHIMERA has the advantage of inducing precise non‐surgical head impacts without restricting head motion, thus inducing TBI relevant to a real‐world scenario. Using CHIMERA, we showed that repetitive mild TBI in a mouse model of amyloidosis led to neuropathological changes including neuroinflammation, fear memory deficits, and accumulation of soluble high molecular weight Aβ oligo/fibril. In the current study, we aim to study if CHIMERA TBI exacerbates tau pathologies, by inducing moderate/severe TBI (msTBI) to rTg4510 mice. Method 4‐mo male rTg4510 mice were used for this study. For the test group, a single msTBI TBI was induced at 4.0 J impact energy, with CHIMERA interface. For sham group, the animals received only anesthesia but no impact. 8 out of 13 animals survived the moderate/severe TBI procedure (38% mortality). The surviving animals were kept for 2‐mo, and the brain tissues were harvested for analysis using immunohistochemistry and Western blotting for multiple tau epitopes, neuroinflammation, and axonal injury. Blood samples were collected biweekly for biomarker analysis. Result TBI animals showed a significant increase duration of loss of righting. Histological analyses indicated significant microgliosis (Iba1) and axonal injury (Neurosilver) at white matter (optic tract), but no significant change in neuronal number (NeuN), astrocytes (GFAP), endothelial cells (CD31), or blood brain barrier integrity (IgG). There was a significant increase of one p‐tau epitope (PHF1), but not others (CP13, AT8, MC1, RZ3, or DA9). TBI also reduced the level of an inactive form of GSK‐3b (p‐GSK‐3b at S9). Interestingly, TBI animals showed a significant increase of P62 signals particularly at hippocampus, suggesting impaired autophagy. Conclusion Our current findings suggest a single msTBI is sufficient to induce p‐tau in rTg4510 mice, possibly through a reduction of inactive GSK‐3b. In addition, increased P62 signals may indicate impaired autophagy, which may lead to increased accumulation of neurodegenerative proteins at a later stage. More work has to be done to confirm long‐term tau and autophagy changes after TBI.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".