Evidence map›Paper›PMID 39547935›Full record

ArticleMetallomics : integrated biometal science2024

X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.

M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly

Abstract read
In one paragraph

Article in Metallomics : integrated biometal science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

M Jake PushieDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.ORCID 0000-0001-7494-5427
Nicole J SylvainDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.ORCID 0000-0002-2762-2454
Huishu HouDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Nicole PendletonDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Richard WangCollege of Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Liam ZimmermannCollege of Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Maxwell PallyCollege of Arts & Science, Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Francisco S CayabyabDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Lissa PeelingDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Michael E KellyDivision of Neurosurgery, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.ORCID 0000-0002-3278-2620

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen, KEITH O HODGSON · 2020 to 2026
$43.3M
Department of Surgery Resident Research AwardNIGMS NIH HHS P30 GM133894University of Saskatchewan College of Medicine Research Award
6 · The paper itself

Abstract

The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

Indexed as

BrainStrokeTrace ElementsAnimalsHumansMaleMiceSpectrometry, X-Ray EmissionTrace Elementsbrain metalsischaemiastroketrace element imagingX-ray fluorescence microscopy

Identifiers

PMID39547935
PMCPMC11631071

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.