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Record W4403382598 · doi:10.1073/pnas.2417137121

Sensors in the microvascular web: Vital but vulnerable

2024· letter· en· W4403382598 on OpenAlexafffund
Baptiste Lacoste

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2024
Typeletter
Languageen
FieldEngineering
TopicAdvanced Chemical Sensor Technologies
Canadian institutionsOttawa HospitalUniversity of Ottawa
FundersInstitute of Neurosciences, Mental Health and AddictionCanadian Institutes of Health ResearchU.S. Department of Defense
KeywordsSimple (philosophy)Computer scienceMeaning (existential)Human–computer interactionNeuroscienceBiologyPsychologyEpistemology

Abstract

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Why is the brain so reliant on proper regulation of its own blood stream, down to the tiniest blood vessels?Neuroscientists agree that the brain is rather small, compared to the liver for instance.On average, an adult human brain weighs ~2% of the body mass, yet its metabolism accounts for 50% of total body glucose consumption.The cardiac output directed to the brain is 15 to 20% in healthy adults ( 1 ), meaning that about 20% of blood volume expulsed by the heart's left ventricle at each beat contains energy for brain needs.Who is the culprit in such exorbitant expenses?Neuronal activity.Maintaining neuronal excitability and generating action potentials consumes >90% of all energy available to the brain, and brain cells need constant oxygen supply ( 2 ).However, nature did not provide the brain with efficient energy storage.This is where proper cerebral blood flow (CBF) comes into play, since it is the only way for brain cells to obtain oxygen and glucose for producing adenosine triphosphate (ATP).It is also why the adult brain is densely vascularized, with a total capillary length of several hundred kilometers within a 1.5 L volume ( 3 ).Interruptions in CBF, even transiently, have harmful consequences for brain health, either through acute ischemic injuries, such as strokes, or via smaller, more insidious lesions in capillary beds that can lead to dementia ( 4 , 5 ).In this context, it is crucial to better understand the biological mechanisms at play in CBF regulation, from large supply arteries and arterioles down to the finest capillary networks irrigating the neuropil.It is also essential to comprehend what happens to the fine-tuning processes in pathologies that affect the integrity of capillary beds.In an imaging tour-deforce, Bonney et al. ( 6) demonstrate how a precise injury in the capillary network of the mouse brain can have broader effects on CBF by affecting flow through upstream control points in the microvascular tree-a finding with important implications for mechanisms of small vessel disease.Identifying adaptative (and maladaptive) mechanisms is a key step toward the development of therapeutic approaches for neurological disorders involving microvascular dysfunction.The brain vasculature is structurally and functionally complex, highly specialized in many ways ( 7 -9 ) and is tied to a variety of neurological disorders and age-related processes ( 10 ).Before taking a closer look at the new findings by Bonney et al., let's get a bird's eye view of current knowledge on CBF regulation at various scales.Pioneering work reviewed elsewhere ( 11 ) has shown that CBF involves structural and functional ensembles of closely interacting neuronal, vascular, perivascular, and glial cells, as well as signaling pathways ensuring intercellular communication.In simple terms, the phenomenon of neurovascular coupling (NVC), as classically defined, involves CBF elevations in response to elevations in neuronal activity in local brain regions "in order to match" the metabolic needs of neurons ( 8 ).Why the quotation marks?Because this statement is either wrong or overly reductionist.First, there is no determinism in CBF regulation, but a rather poorly matched vasodilation and unconfined blood delivery (also known as functional hyperemia) to

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.377
Threshold uncertainty score0.910

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 studies0.0000.001
Scholarly communication0.0000.000
Open science0.0020.000
Research integrity0.0000.002
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 head0.023
GPT teacher head0.256
Teacher spread0.233 · 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".

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Citations0
Published2024
Admission routes2
Has abstractyes

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