Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice

Ethan P. Glaser; Timothy J. Kopper; William M. Bailey; Hassan K. Kashif; Reena Kumari

doi:10.1038/s41598-024-84936-6

Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice

Ethan P. Glaser, Timothy J. Kopper, William M. Bailey, Hassan K. Kashif, Reena Kumari, Andrew N. Stewart, John C. Gensel

Nature Portfolio (2025) • Volume 15, Issue 1, Pages 1-1

Empirical-PreclinicalPreclinical-AnimalPDF AvailableGrade Eligible⚠️ Moderate Risk Flags

Overall Assessment

Adequate Methodological Quality

Assessment created by PaperScorers Medical AI v0.1.0 on Dec 22, 2025

C

60/100

Key Takeaways

•cPLA2 KO BMDMs resist myelin-potentiated ROS/NO and neurotoxicity in vitro (Fig.1).
•HSCT 10.5 Gy yields ~85% leukocyte chimerism with minimal CNS infiltration (Fig.2).
•cPLA2 KO chimeras show ~10× lower leukocyte cPLA2; spinal cord cPLA2 reduced at 7 dpi (Fig.3).
•No differences in BMS, CatWalk, ladder at up to 6 WPI between KO and WT chimeras (Fig.4).
•No differences in tissue sparing or intralesional axons at 6 WPI (Fig.5).

Conclusion

Infiltrating MDM cPLA2 is dispensable for locomotor recovery and tissue sparing after SCI in female mice despite in vitro effects.

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Quality Dimensions

Bias & Integrity

COI handling, outcome switching, selective reporting

B-72

Methods Rigour

Protocol clarity, sampling, controls

C62

External Validity

Generalisability, setting, population

D45

Transparency & Reproducibility

Data/code/materials availability, preregistration

C60

Significance & Novelty

Contribution vs prior art; context if known

C-55

Statistical Validity

Models, assumptions, multiplicity, CI priority

C-55

Integrity & Transparency

Integrity checks

P-hacking risk?

?

None suspected

Signs of selective hypothesis testing or analysis choices that could inflate false positive rates.

Outcome switching?

?

Review recommended

Evidence that primary outcomes were changed during or after the study, potentially distorting results.

Conflict of interest?

?

None suspected

Authors have financial or other relationships that could bias research findings.

Data integrity issues?

?

None suspected

Concerns about the accuracy, completeness, or authenticity of the reported data.

Open science signals

Research data

?

Open access

Raw data used in the analyses is publicly available or accessible upon request.

Analysis code

?

Not shared

Code or scripts used to analyze the data are shared for reproducibility.

Study materials

?

Not shared

Protocols, questionnaires, and other materials are publicly available.

Premise

Primary Research Question

Does MDM cPLA2 impair recovery after SCI in female mice?

Hypothesis

cPLA2 activation in MDMs contributes to secondary injury after SCI.

Hypothesis is Falsifiable

✓Yes

KO vs WT chimeras tested on predefined behavioural/histology endpoints.

PICO Framework

Population✓Yes

Female C57BL/6J mice with T9 contusion SCI.

Intervention✓Yes

HSC transplantation from cPLA2 KO vs WT donors after 10.5 Gy.

Comparison✓Yes

WT→WT chimera controls versus KO→WT chimeras.

Outcome✓Yes

BMS, CatWalk, ladder; tissue sparing and axon density.

Literature Positioning

Literature Review Balanced

Well covered

Summarises conflicting prior cPLA2 SCI studies (benefit vs harm).

Evidence: Discussion

Research Gap Clearly Stated

Well covered

Role of cPLA2 in infiltrating MDMs after SCI unclear.

Evidence: Intro

Stated Contribution Clear

Well covered

Shows cPLA2 needed for myelin-potentiated macrophage activation in vitro but not recovery in vivo.

Evidence: Abstract

Study Provenance

Peer reviewed venueGrant funding disclosedNo conflicts declaredAffiliations listed

Authors & Affiliations

University of Kentucky (SCoBIRC), University of Colorado Anschutz.

Funding Statement

Craig H. Neilsen Foundation #651996; NIH NINDS F31NS105443, F30NS129251, R01NS116068.

Conflicts of Interest

Authors declare no competing interests.

Peer Review

✓Scientific Reports (Nature Research), 2025.

Evidence: journal header

Methodological Assessment

Preclinical StudyARRIVEPreclinical

6 applicable checklist items.

Yes 3 · No 3

✗

Randomisation Reported

No random allocation to donor groups reported.

Evidence: Methods HSCT/SCI; absent statement

✓

Blinding Reported

Outcome assessors blinded for BMS, CatWalk, ladder, histology.

Evidence: Methods Behaviour/Histology

✗

Sample Size Calculation Reported

No power or sample size calculation reported.

Evidence: Methods Statistics

✓

Inclusion/Exclusion Criteria Clear

A priori exclusion (BMS≥3 at 1 dpi); endpoint cPLA2 expression check.

Evidence: Table 1

✓

Animal Model Justified

T9 65 kDyn contusion is standard and justified; HSCT dose optimised.

Evidence: Methods SCI; Fig. 2

✗

Multiplicity Controlled

Multiple outcomes tested; no correction stated.

Evidence: Methods Statistics; Results Fig.4–5

Modules without applicable checklist items (9)

These designs were fully marked as not applicable but remain available for reference.

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Study Overview

Study Design

Preclinical Animal

Primary classification used to evaluate this research.

Population

Female C57BL/6J mice with T9 contusion SCI; WT recipients of WT or cPLA2−/− donor HSCs; in vitro BMDMs from WT/KO.

Brief summary of who or what was studied.

Sample Size

27

Number of participants included in the study analyses.

Study Arms

2 arms

Total number of intervention or comparison groups.

Pre-registration

Not registered

Indicates whether the protocol or trial was registered before data collection.

Randomisation

None reported

How participants were allocated to groups: None (no randomisation), Simple (random order), Blocked (groups balanced in blocks), Stratified (balanced within subgroups), Adaptive (allocation adjusted based on previous enrollments).

Blinding

Single blind

Who was unaware of group assignments: None (everyone knew), Single blind (participants didn't know their group), Double blind (participants and researchers didn't know), Triple blind (also outcome assessors didn't know).

Analysis Set

Other

Which participants were included in analysis: ITT (all randomized, regardless of adherence), mITT (modified ITT, excluding some for valid reasons), Per protocol (only those who completed as planned), As treated (grouped by actual treatment received), Other (alternative approach).

Follow-up

6 weeks

Duration of observation or follow-up for outcomes.

Primary Outcome

Unclear whether the primary outcome was pre-specified.

Effect Size

ANOVA F: BMS scores F(1,25)=0.268, p=0.609

Reviewer Notes

Animal SCI chimera experiment comparing KO vs WT donor HSCs; locomotion and histology over 6 weeks; in vitro assays are ancillary.

Publication Details

DOI

10.1038/s41598-024-84936-6

Published

January 2, 2025

Citations

236 citations

FWCI

1157.85

External Resources

DOI Link OpenAlex

Disclaimer: This assessment is generated by AI and should not be the sole basis for clinical or research decisions. Always review the original paper and consult with domain experts.

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