Evidence map›Paper›PMID 41667048›Full record

ArticleExperimental neurology2026

DLK inhibition has sex-specific effects on neuroprotection and locomotor recovery after spinal cord injury.

John C Aldrich, Samantha M Alman, Sydney E Lee, Ashley R Scheinfeld, Chelsea C Zhang, Averi L Pike, Fiona C Bremner, Olivia Calderon, Sunil Goodwani, William J Ray and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 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

11 authors.

John C AldrichDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Samantha M AlmanDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Sydney E LeeDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Ashley R ScheinfeldDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Chelsea C ZhangDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Averi L PikeDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Fiona C BremnerDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
Olivia CalderonBelfer Neurodegeneration Consortium, Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Sunil GoodwaniBelfer Neurodegeneration Consortium, Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
William J RayBelfer Neurodegeneration Consortium, Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Andrew D GaudetDepartment of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA; Interdisciplinary Neuroscience Program, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: andrew.gaudet@utexas.edu.

Funding

Circadian control of neuroinflammation after spinal cord injuryR01NS131806 · UNIVERSITY OF TEXAS AT AUSTIN · 2025 to 2025
$441k
NINDS NIH HHS R01 NS131806
6 · The paper itself

Abstract

Spinal cord injury (SCI) causes devastating functional deficits, in part due to neuroinflammation, oxidative stress, and excitotoxicity that drive death of lesion-adjacent viable neurons. Dual leucine zipper kinase (DLK) is a neuron-enriched kinase that responds to cellular stress by activating the c-Jun N-terminal kinase (JNK) pathway, driving both stress-responsive gene expression and neuronal apoptosis. We hypothesized that SCI would robustly activate DLK signaling and that acute pharmacological inhibition of DLK would suppress JNK pathway activation, thereby enhancing neuroprotection and locomotor recovery in our mouse model of moderate contusion SCI. Using western blotting, we observed that SCI induced strong and sustained activation of the JNK pathway in the injured spinal cord starting at 4 h post-injury through 7 days. Complementary analysis of single-nucleus RNA-seq revealed that DLK expression is highly enriched in neurons across all injury phases. Following SCI, neurons exhibited robust, time-dependent upregulation of multiple DLK-responsive transcripts, consistent with sustained pathway activation during the acute and subacute periods. Systemic treatment with the selective DLK inhibitor IACS-52825 effectively suppressed intraspinal JUN activation in a dose-dependent manner. However, unexpectedly, treatment delayed functional recovery and expanded lesion volume by 71% in male mice with no significant effect in females. These findings highlight the complex roles of DLK signaling after SCI, revealing a need to understand the sex-specific molecular mechanisms that modulate injury outcomes. Future studies should further optimize timing, location, and cellular targeting of DLK therapeutic strategies to improve neuroprotection and neurologic recovery after SCI.

Indexed as

LocomotionMAP Kinase Kinase KinasesNeuroprotectionNeuroprotective AgentsRecovery of FunctionSex CharacteristicsSpinal Cord InjuriesAnimalsFemaleMaleMiceMice, Inbred C57BLMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12Neuroprotective Agentsapoptosisc-Jun N-terminal kinase pathwaydual-leucine zipper kinaseneuroprotectionneurotraumasex differencesspinal cord injury

Identifiers

PMID41667048
PMCPMC13014413

What Socratic holds

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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.