Evidence map›Paper›PMID 39382610›Full record

ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2024

Extracellular Vesicles from Mesenchymal Stem Cells Reverse Neuroinflammation and Restore Motor Coordination in Hyperammonemic Rats.

Paula Izquierdo-Altarejos, Mar Martínez-García, Iván Atienza-Pérez, Alberto Hernández, Victoria Moreno-Manzano, Marta Llansola, Vicente Felipo

Abstract read
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In one paragraph

Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. HucMSCs-Derived Extracellular Vesicles Deliver RPS27A Protein to Manipulate the MDM2-P53 Axis and Ameliorate Neurological Dysfunction in Parkinson's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  6. 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

7 authors.

Paula Izquierdo-AltarejosLaboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Mar Martínez-GarcíaLaboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Iván Atienza-PérezLaboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Alberto HernándezOptical and Confocal Microscopy Service, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Victoria Moreno-ManzanoNeuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Marta LlansolaLaboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Vicente FelipoLaboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain. vfelipo@cipf.es.

Funding

Conselleria de Educación de la Generalitat Valenciana PROMETEOII/2018/051 and CIPROM 2021/082Generalitat Valenciana OP ERDF of Comunitat Valenciana 2014-2020Ministerio de Ciencia e Innovación PID2020-113388RB-I00-AEI/10.13039/501100011033Ministerio de Ciencia, Innovación y Universidades FPU17/01698
6 · The paper itself

Abstract

Cirrhotic patients may show minimal hepatic encephalopathy (MHE), with mild cognitive impairment and motor deficits. Hyperammonemia and inflammation are the main contributors to the cognitive and motor alterations of MHE. Hyperammonemic rats reproduce these alterations. There are no specific treatments for the neurological alterations of MHE. Extracellular vesicles from mesenchymal stem cells (MSC-EVs) are promising to treat inflammatory and immune diseases. We aimed to assess whether treatment of hyperammonemic rats with MSC-EVs reduced neuroinflammation in cerebellum and restored motor coordination and to study the mechanisms involved. The effects of MSC-EVs were studied in vivo by intravenous injection to hyperammonemic rats and ex vivo in cerebellar slices. Motor coordination was analyzed using the beam walking test. Effects on neuroinflammation were assessed by immunohistochemistry, immunofluorescence and Western blot. Injection of MSC-EVs reduced microglia and astrocytes activation in cerebellum and restored motor coordination in hyperammonemic rats. Ex vivo experiments show that MSC-EVs normalize pro-inflammatory factors, including TNFα, NF-kB activation and the activation of two key pathways leading to motor incoordination (TNFR1-NF-kB-glutaminase-GAT3 and TNFR1-CCL2-BDNF-TrkB-KCC2). TGFβ in the EVs was necessary for these beneficial effects. MSC-EVs treatment reverse neuroinflammation in the cerebellum of hyperammonemic rats and the underlying mechanisms leading to motor incoordination. Therapy with MSC-EVs may be useful to improve motor function in patients with MHE.

Indexed as

Extracellular VesiclesHyperammonemiaMesenchymal Stem CellsRats, WistarAnimalsCerebellumHepatic EncephalopathyMaleNeuroinflammatory DiseasesRatsExtracellular vesiclesGABAergic neurotransmissionHepatic encephalopathyMesenchymal stem cellsMotor coordinationNeuroinflammation

Identifiers

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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.