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Record W3134401744 · doi:10.21203/rs.3.rs-271852/v1

Developing Brain-Strain-Based Scaling to Inform the Clinical Relevance of Mouse Models of Concussion Induced by Rotation

2021· preprint· en· W3134401744 on OpenAlexafffund
Xingyu Liu, Lihong Lu, Kewei Bian, Arthur Brown, Haojie Mao

Bibliographic record

VenueResearch Square · 2021
Typepreprint
Languageen
FieldMedicine
TopicTraumatic Brain Injury Research
Canadian institutionsRobarts Clinical TrialsWestern University
FundersNatural Sciences and Engineering Research Council of CanadaCanada Research Chairs
KeywordsConcussionTraumatic brain injuryHuman brainGenetically modified mouseNeuroscienceMedicinePoison controlPhysical medicine and rehabilitationInjury preventionTransgeneBiologyGenePsychiatryGeneticsMedical emergency

Abstract

fetched live from OpenAlex

Abstract Background Laboratory animal experiments are an invaluable tool for studying mild traumatic brain injury (mTBI)/concussion. Among them, rodent neurotrauma experiments have been most widely used, as transgenic and gene targeting technologies in mice allow us to test the roles of different genes in recovery from brain injury. Furthermore, the clinical relevance of rodent concussion studies can be improved by using these technologies to study concussions in animals that carry the human versions of genes known to play a role in neurological disease. However, delivering concussion injuries to the mice that are relevant to real-world human head impacts is challenging, as the mouse and human heads are dramatically different in shape and size. In the vast majority of mouse concussion experiments, the pathological and behavioral consequences of the injuries are evaluated without considering whether the injury model produces brain stretches (maximum principal strains) of the same magnitude as those experienced by human brains undergoing similar impacts. Methods We conducted a total of 201 computational simulations to understand both human and mouse brain strains that are directly linked to neuronal damage during closed-head concussive impacts. To represent real-world human head impacts we simulated mouse head impacts with durations of 1.5 ms (Type 1 scaling), followed by simulations with durations between 1 and 2 ms (Type 2), and finally, simulations with durations from 0.75 to 4.5 ms (Type 3) to develop scaling between human and mouse, as well as to reveal the predicted effects of small and large changes in impact durations on brain strain. Results Guided by these simulations we calculated that peak rotational velocities in mice could be achieved by scaling human peak rotational velocities with factors of 5.8, 4.6, and 6.8, for flexion/extension, lateral bending, and axial rotation, respectively, to reach equal brain strains between human and mouse. The effects of impact durations on scaling were also calculated and longer-duration mouse head impacts needed larger scaling factors to reach equal strain. Conclusions The scaling method will help us to create brain injury in the mouse with brain strain loading equivalent to those experienced in real-world human head impacts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

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.

Opus teacher head0.343
GPT teacher head0.516
Teacher spread0.174 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2021
Admission routes2
Has abstractyes

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