Evidence map›Paper›PMID 40545497›Full record

ArticleSignal transduction and targeted therapy2025

Uncovering injury-specific proteomic signatures and neurodegenerative risks in single and repetitive traumatic brain injury.

Sarah Mantash, Soulaimane Aboulouard, Hassan Dakik, Yanis Zirem, Lydia Ziane-Chaouche, Ali Nehme, Khalil Mallah, Marya El-Kurdi, Naify Ramadan, Isabelle Fournier and 3 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Parkin protects against traumatic brain injury through regulating mitochondrial quality control.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  6. Article
  7. Neural Immunoglobulins Shape Brain Circuits.The European journal of neuroscience · 2025
    Review
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

13 authors.

Sarah Mantash *Department of Experimental pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Soulaimane Aboulouard *Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Univ. Lille, Inserm, CHU Lille, U1192, Lille, France.
Hassan Dakik *Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Yanis Zirem *Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Univ. Lille, Inserm, CHU Lille, U1192, Lille, France.
Lydia Ziane-ChaoucheLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Univ. Lille, Inserm, CHU Lille, U1192, Lille, France.
Ali NehmeDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Khalil MallahDepartment of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC, USA.ORCID 0000-0001-7622-8106
Marya El-KurdiDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Naify RamadanDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Isabelle FournierLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Univ. Lille, Inserm, CHU Lille, U1192, Lille, France.ORCID 0000-0003-1096-5044
Kazem ZibaraDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.ORCID 0000-0002-9887-072X
Firas KobeissyDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. firasko@gmail.com.
Michel SalzetLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Univ. Lille, Inserm, CHU Lille, U1192, Lille, France. Michel.salzet@univ-lille.fr.ORCID 0000-0003-4318-0817

Funding

Training the Trainers: Building Institutional Data Science Capacity to Support Health Disparities ResearchU54MD007602 · NIMHD · MOREHOUSE SCHOOL OF MEDICINE · PI Kevin Sean Kimbro · 2018 to 2026
$47.6M
NIMHD NIH HHS U54 MD007602
6 · The paper itself

Abstract

Traumatic brain injury (TBI) is a major public health concern associated with an increased risk of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and chronic traumatic encephalopathy, yet the underlying molecular mechanisms in repetitive TBI remain poorly defined. This study investigates proteomic and behavioral changes following single and repetitive mild TBI in a mouse model, focusing on molecular alterations in the cortex and hippocampus across acute (48 h) and subacute (1 week) stages. Using shotgun proteomics and bioinformatics approaches, including weighted gene co-expression network analysis (WGCNA) and machine learning, we analyzed the proteomic landscapes of TBI-affected brain regions including the hippocampus and the cortex. We assessed motor and cognitive outcomes at 2-, 7-, and 30-days post-injury to explore functional impairments associated with observed molecular changes. Our findings reveal spatio-temporal injury- and time-specific proteomic changes, with a single TBI promoting neuroprotective and repair mechanisms, while repetitive TBI exacerbating neuronal damage and synaptic deficits in the hippocampus. Key deregulated proteins, including Apoa1, ApoE, Cox6a1, and Snca, were linked to neurodegenerative pathways, suggesting molecular connections between TBI and diseases like AD and PD. Behavioral assessments indicated that repetitive TBI significantly impaired motor and cognitive functions, with recovery in motor function by day 30, whereas cognitive deficits persisted. This study provides a detailed analysis of the proteomic and behavioral consequences of TBI, identifying molecular networks as potential biomarkers or therapeutic targets for mitigating long-term cognitive decline associated with repetitive head trauma. These findings underscore the importance of mitochondrial and synaptic integrity in TBI response and suggest that targeting these pathways could reduce neurodegenerative risk following repetitive TBI.

Indexed as

Alzheimer DiseaseBrain Injuries, TraumaticNeurodegenerative DiseasesProteomicsAnimalsDisease Models, AnimalHippocampusHumansMaleMice

Identifiers

PMID40545497
PMCPMC12183312

What OpenQuestion 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 OpenQuestion graph.