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Record W4210308805 · doi:10.1093/braincomms/fcac019

Characterization of neuroinflammatory positron emission tomography biomarkers in chronic traumatic encephalopathy

2022· article· en· W4210308805 on OpenAlexafffund
Cassis Varlow, Ashley C. Knight, Paul McQuade, Neil Vasdev

Bibliographic record

VenueBrain Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicTraumatic Brain Injury and Neurovascular Disturbances
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingCanada Research ChairsAzrieli FoundationSchool of Medicine, Boston UniversityCanada Foundation for InnovationTarget ALSGeorgetown UniversityCanadian Institutes of Health ResearchU.S. Department of Veterans Affairs
KeywordsTranslocator proteinChronic traumatic encephalopathyEncephalopathyTraumatic brain injuryMonoamine oxidasePathologyMedicinePositron emission tomographyInternal medicineNuclear medicineChemistryMicrogliaConcussionPoison controlInflammationBiochemistryEnzymePsychiatry

Abstract

fetched live from OpenAlex

Abstract Chronic traumatic encephalopathy is a neurological disorder associated with head trauma and is confirmed upon autopsy. PET imaging of chronic traumatic encephalopathy may provide a means to move towards ante-mortem diagnosis and therapeutic intervention following brain injuries. Characterization of the neuroinflammatory PET biomarkers, 18 kDa translocator protein and monoamine oxidase-B was conducted using [3H]PBR-28 and [3H]L-deprenyl, respectively, in post-mortem chronic traumatic encephalopathy brain tissue. [3H]PBR-28 displayed high specific binding in both chronic traumatic encephalopathy (95.40 ± 1.87%; n = 11 cases) and healthy controls (89.89 ± 8.52%, n = 3 cases). Cell-type expression of the 18 kDa translocator protein was confirmed by immunofluorescence to microglia, astrocyte and macrophage markers. [3H]L-deprenyl also displayed high specific binding in chronic traumatic encephalopathy (96.95 ± 1.43%; n = 12 cases) and healthy controls (93.24 ± 0.43%; n = 2 cases), with the distribution co-localized to astrocytes by immunofluorescence. Saturation analysis was performed to quantify the target density of the 18 kDa translocator protein and monoamine oxidase-B in both chronic traumatic encephalopathy and healthy control tissue. Using [3H]PBR-28, the target density of the 18 kDa translocator protein in healthy controls was 177.91 ± 56.96 nM (n = 7 cases; mean ± standard deviation); however, a highly variable target density (345.84 ± 372.42 nM; n = 11 cases; mean ± standard deviation) was measured in chronic traumatic encephalopathy. [3H]L-deprenyl quantified a monoamine oxidase-B target density of 304.23 ± 115.93 nM (n = 8 cases; mean ± standard deviation) in healthy control tissue and is similar to the target density in chronic traumatic encephalopathy tissues (365.80 ± 128.55 nM; n = 12 cases; mean ± standard deviation). A two-sample t-test determined no significant difference in the target density values of the 18 kDa translocator protein and monoamine oxidase-B between healthy controls and chronic traumatic encephalopathy (P > 0.05), albeit a trend towards increased expression of both targets was observed in chronic traumatic encephalopathy. To our knowledge, this work represents the first in vitro characterization of 18 kDa translocator protein and monoamine oxidase-B in chronic traumatic encephalopathy and reveals the variability in neuroinflammatory pathology following brain injuries. These preliminary findings will be considered when designing PET imaging studies after brain injury and for the ultimate goal of imaging chronic traumatic encephalopathy in vivo.

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)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.949
Threshold uncertainty score0.494

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.024
GPT teacher head0.276
Teacher spread0.251 · 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.

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

Citations8
Published2022
Admission routes2
Has abstractyes

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