Evidence map›Paper›PMID 41589731›Full record

ArticleThe journal of trauma and acute care surgery2026

Role of peptidylarginine deiminase 2 in a murine model of traumatic brain injury.

Zaiba Shafik Dawood, Marjorie R Liggett, Bowen Wang, Kaijie Zhang, Guang Jin, Wenlu Ouyang, Daniel C Couchenour, Alvin Anand, Aleezeh Shaikh, Kiril Chtraklin and 4 more

Abstract read
In one paragraph

Article in The journal of trauma and acute care surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Zaiba Shafik DawoodFrom the Department of Surgery (Z.S.D., M.R.L., B.W., K.Z., G.J., D.C.C., A.A., A.S., K.C., B.L., D.J., H.B.A.), Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and Department of Surgery (W.O., Y.L.), University of Michigan Medical School, Ann Arbor, Michigan.
Marjorie R Liggett
Bowen Wang
Kaijie Zhang
Guang Jin
Wenlu Ouyang
Daniel C Couchenour
Alvin Anand
Aleezeh Shaikh
Kiril Chtraklin
Baoling Liu
Dinesh Jaishankar
Yongqing Li

Funding

PAD2 and CitH3 in Pathogenesis of Sepsis-induced ALIR01HL155116 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALAM, HASAN B, LI, YONGQING · 2021 to 2024
$2.1M
NHLBI NIH HHS R01 HL155116
6 · The paper itself

Abstract

introductionTraumatic brain injury (TBI) is among the leading causes of death and disability worldwide. Studies have linked peptidylarginine deiminases (PADs) with TBI outcomes. However, nonspecific PAD inhibition makes it difficult to decipher the exact role of specific PAD enzymes in neurotrauma. Since both PAD2 and PAD4 have been linked with neurodegeneration, we sought to clearly establish their roles in TBI.

methodsMale mice (11-14 weeks) were subjected to controlled cortical impact TBI (n = 5/group). Experimental groups included wild-type plus TBI (WT-TBI), PAD2 knockout plus TBI (PAD2-KO-TBI), PAD4 knockout plus TBI (PAD4-KO-TBI), and PAD2/4 double knockout plus TBI (PAD2/4-DKO-TBI). Twenty-four hours post-TBI, frozen brain sections were stained (Nissl and immunofluorescence) to determine lesion size and expression of PAD2 and PAD4. We also assessed the impact of PAD2-KO on neurologic severity scores (1-8 days post-TBI) and visuospatial learning using the Morris water maze test (21-30 days post-TBI).

resultsOverall, PAD2-KO-TBI and PAD2/4-DKO-TBI animals displayed significantly smaller brain lesion sizes than WT-TBI (p = 0.005 and 0.005, respectively) and PAD4-KO-TBI (p = 0.005 and 0.004, respectively). However, there was no significant difference in lesion size between the PAD4-KO-TBI and WT-TBI (p = 0.880) groups. Analysis of archived snRNA-seq data and immunofluorescence staining 24 hours post-TBI showed upregulation of PAD2 (primarily in astrocytes) in WT-TBI compared with sham (p = 0.048), whereas PAD4 was undetectable. Overall, PAD2-KO-TBI had a significantly lower neurologic severity score on postinjury days 1 to 6 compared with WT-TBI (all p < 0.05) group. Moreover, Morris water maze test demonstrated that the cumulative cued and noncued spatial learning was worse in WT-TBI compared with PAD2-KO-TBI (p < 0.05) animals.

conclusionOur results suggest that PAD2, but not PAD4, blockade can improve outcomes following TBI, which justifies its exploration as a potential target for novel neuroprotective therapies.

Indexed as

Brain Injuries, TraumaticHydrolasesProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2AnimalsBrainDisease Models, AnimalMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutProtein-Arginine Deiminase Type 4HydrolasesPadi2 protein, mousepeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2Protein-Arginine Deiminase Type 4miceneutrophil extracellular trappeptidylarginine deaminasessecondary brain injuryTraumatic brain injury

Identifiers

PMID41589731
PMCPMC13596131

What Socratic holds

Textmetadata
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.