Evidence map›Paper›PMID 40769386›Full record

ArticleExperimental neurology2025

Sex-dependent effects of peptidylarginine deiminases on neutrophil function and long-term outcomes after spinal cord injury.

Shelby K Reid, Ashley V Tran, Miranda E Leal-Garcia, Sachit Devaraj, Mustafa Ozturgut, Dylan A McCreedy

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Shelby K ReidTexas A&M Institute for Neuroscience, Texas A&M University, 3474 TAMU, College Station, TX 77843, USA; Department of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: shelbykrr@tamu.edu.
Ashley V TranDepartment of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: ashleyvitran@tamu.edu.
Miranda E Leal-GarciaDepartment of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: mleal@bio.tamu.edu.
Sachit DevarajDepartment of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: sachitd97@tamu.edu.
Mustafa OzturgutDepartment of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: mozturgut@tamu.edu.
Dylan A McCreedyTexas A&M Institute for Neuroscience, Texas A&M University, 3474 TAMU, College Station, TX 77843, USA; Department of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843, USA. Electronic address: dmccreedy@bio.tamu.edu.

Funding

Supplement: L-selectin shedding as a novel therapeutic strategy to mitigate acute secondary damage after spinal cord injuryR01NS122961 · NINDS · TEXAS A&M UNIVERSITY · PI MCCREEDY, DYLAN A. · 2021 to 2025
$2.0M
NINDS NIH HHS R01 NS122961
6 · The paper itself

Abstract

Traumatic spinal cord injury (SCI) initiates an influx of peripheral immune cells to the spinal cord parenchyma that compound tissue damage and restrict functional recovery. Neutrophils infiltrate the spinal cord within the first day after injury, releasing extracellular traps (NETs) comprised of decondensed DNA, modified histones, and granule enzymes, that can worsen tissue damage. Peptidylarginine demininases (PADs), particularly PAD4, have been indicated as mediators of NET formation by facilitating the decondensation of nuclear chromatin via histone citrullination. Though PADs have been shown to be regulated by sex hormones, sex-differences in PAD regulation of neutrophil function in the context of CNS injury have yet to be explored. In this work, we investigated the role of PADs in recovery after SCI using Cl-amidine, a pan-PAD inhibitor. Strikingly, Cl-amidine treated mice exhibited sex-dependent changes to motor function, body weight, and white matter sparing after SCI. Acutely, Cl-amidine treated mice had reduced NET accumulation in the blood and decreased spinal cord neutrophil granularity. Analysis of publicly available scRNA-seq data revealed that female bone marrow neutrophils exhibited elevated Padi4 expression relative to their male counterparts. We then utilized Padi4 knockout (Padi4

Indexed as

NeutrophilsProtein-Arginine DeiminasesRecovery of FunctionSex CharacteristicsSpinal Cord InjuriesAnimalsFemaleMaleMiceMice, Inbred C57BLMice, KnockoutOrnithineProtein-Arginine Deiminase Type 4N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amideOrnithinepeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Functional motor recoveryInnate immunityNeuroinflammationNeurotraumaNeutrophil extracellular trapsNeutrophilsPAD4Peptidylarginine deiminasesSex differencesSpinal cord injury

Identifiers

PMID40769386
PMCPMC13277984

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Registered trials

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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 OpenQuestion graph.