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Record W3203137286 · doi:10.3389/fnagi.2021.742632

Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives

2021· review· en· W3203137286 on OpenAlexaff
Nicole Schwab, Emily Leung, Lili‐Naz Hazrati

Bibliographic record

VenueFrontiers in Aging Neuroscience · 2021
Typereview
Languageen
FieldMedicine
TopicTelomeres, Telomerase, and Senescence
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsSenescenceExcitotoxicityTraumatic brain injuryNeuroinflammationNeuroscienceDNA damageChronic traumatic encephalopathyTauopathyInflammationGliosisDementiaMedicineDiseaseBiologyBioinformaticsProgrammed cell deathImmunologyNeurodegenerationPoison controlPathologyPsychiatryConcussionInternal medicineGeneticsInjury preventionApoptosis

Abstract

fetched live from OpenAlex

Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, microgliosis, excitotoxicity, and proteinopathy - however the pathophysiological mechanisms activating these pathways after mTBI remains controversial and unclear. Emerging research suggests DNA damage-induced cellular senescence as a possible driver of mTBI-related sequalae. Cellular senescence is a state of chronic cell-cycle arrest and inflammation associated with physiological aging, mood disorders, dementia, and various neurodegenerative pathologies. This narrative review evaluates the existing studies which identify DNA damage or cellular senescence after TBI (including mild, moderate, and severe TBI) in both experimental animal models and human studies, and outlines how cellular senescence may functionally explain both the molecular and clinical manifestations of TBI. Studies on this subject clearly show accumulation of various forms of DNA damage (including oxidative damage, single-strand breaks, and double-strand breaks) and senescent cells after TBI, and indicate that cellular senescence may be an early event after TBI. Further studies are required to understand the role of sex, cell-type specific mechanisms, and temporal patterns, as senescence may be a pathway of interest to target for therapeutic purposes including prognosis and treatment.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.956
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.003
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.100
GPT teacher head0.356
Teacher spread0.256 · 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 teacher head, not a consensus.

Study designOther design
Domainnot available
GenreReview

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

Citations32
Published2021
Admission routes1
Has abstractyes

Explore more

Same venueFrontiers in Aging NeuroscienceSame topicTelomeres, Telomerase, and SenescenceFrench-language works237,207