Evidence map›Paper›PMID 41291440›Full record

ArticleThe journal of headache and pain2025

Neuron-derived extracellular vesicles reflect adaptive neuronal responses to cortical spreading depolarization: a biomarker study for migraine.

Melike Sever-Bahcekapili, Canan Cakir-Aktas, Ülkü Güler, Bora Onat, Bengisu Solgun, Mehtap Şahin, Nevin Belder, Şefik Evren Erdener, Bekir Salih, Turgay Dalkara

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Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
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2citing papers in PubMed
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1 · What the graph read from it

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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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Melike Sever-BahcekapiliInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Canan Cakir-AktasInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Ülkü GülerDepartment of Chemistry, Mass Spectrometry Research Laboratory, Hacettepe University, Ankara, Turkey.
Bora OnatBiotechnology Institute, Ankara University, Ankara, Turkey.
Bengisu SolgunInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Mehtap ŞahinInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Nevin BelderBiotechnology Institute, Ankara University, Ankara, Turkey.
Şefik Evren ErdenerInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Bekir SalihDepartment of Chemistry, Mass Spectrometry Research Laboratory, Hacettepe University, Ankara, Turkey.
Turgay DalkaraInstitute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey. t.dalkara@bilkent.edu.tr.

Funding

Ministry of Development-Republic of Türkiye 2016 K121230Türkiye Bilimsel ve Teknolojik Araştırma Kurumu 120C122
6 · The paper itself

Abstract

backgroundSmall extracellular vesicles (EVs) are nano-sized membranous particles transporting bioactive cargo, including proteins. In the central nervous system (CNS), neuron-derived EVs (nEVs) are thought to play roles in synaptic plasticity, metabolic regulation, and neuroinflammation. While their relevance in neurodegenerative and neuroinflammatory disorders is increasingly recognized, their role in migraine pathophysiology remains underexplored.

objectiveThis study aimed to investigate the proteomic signature of nEVs isolated from the cortex of mice subjected to cortical spreading depolarization (CSD), a neurobiological event underlying migraine aura. We sought to identify molecular pathways activated in neurons during CSD and evaluate the potential of nEVs as biomarkers for aura-related brain activity.

methodsCSD was induced either by pinprick in wild type mice or optogenetically in Thy-ChR2-YFP mice. Following brain perfusion and cortical tissue dissociation, total cortical EVs were isolated by ultracentrifugation whereas nEVs were isolated via immunoaffinity capture targeting neuronal L1 cell adhesion molecule (L1CAM) following nickel-based precipitation of total EVs. nEV proteome was analyzed using label-free quantitative mass spectrometry. Identified proteins were subjected to functional enrichment analysis to uncover relevant biological processes.

resultsUnbiased proteomic profiling revealed CSD-associated changes in pathways involved in transcriptional/translational regulation, cytoskeletal dynamics, stress response and metabolism. These exploratory and descriptive findings suggest that neuronal responses to CSD involve adaptive structural and metabolic alterations and are not limited to inflammatory signaling.

conclusionOur results highlight the potential of nEVs as dynamic reporters of cortical neuronal activity in a migraine model. Significant changes in nEV proteome suggest that the neuronal response to CSD extends beyond inflammatory signaling and encompasses adaptive mechanisms aimed at maintaining cellular homeostasis and synaptic integrity. Given their accessibility through peripheral fluids and potential capacity to reflect dynamic changes in neurons, nEVs emerge as promising candidates for investigating pathophysiology and biomarker identification in migraine.

Indexed as

Cerebral CortexCortical Spreading DepressionExtracellular VesiclesMigraine DisordersMigraine with AuraNeuronsAnimalsBiomarkersDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, TransgenicProteomicsBiomarkersBiomarkerCortical spreading depolarizationCytoskeletonExtracellular vesiclesMigraineNeuroinflammationNeuron-derived EVsProteomics

Identifiers

PMID41291440
PMCPMC12649082

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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.