Evidence mapPaperPMID 41664147Full record

ArticleJournal of translational medicine2026

Extracellular vesicles derived from astrocytes pretreated with melatonin promoted neuro-angiogenesis in mice with ischemic medial prefrontal cortex.

Behnaz Mirzaahmadi, Hajar Shafaie, Javad Mahmoodi, Parinaz Haddadi, Ali Hassanzadeh, Russel J Reiter, Farzaneh Fazli, Mohammad Karimipour, Reza Rahbarghazi

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Behnaz MirzaahmadiDepartment of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Hajar ShafaieDepartment of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Daneshghah St. Tabriz, Tabriz, 5166614766, Iran.
Javad MahmoodiNeurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Parinaz HaddadiDepartment of Biochemistry, Faculty of Natural Sciences, Tabriz University, Tabriz, Iran.
Ali HassanzadehDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Russel J ReiterDepartment of Cellular and Structural Biology, Health Science Center, University of Texas, San Antonio, TX, 78229, USA.
Farzaneh FazliDepartment of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Daneshghah St. Tabriz, Tabriz, 5166614766, Iran.
Mohammad Karimipour *Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. karimipourm@yahoo.com.
Reza Rahbarghazi *Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. rezarahbardvm@gmail.com.ORCID http://orcid.org/0000-0003-3864-9166

Funding

Tabriz University of Medical Sciences IR.TBZMED.AEC.1402.020the Vice President of Scientific Technology and Knowledge Council for the Development of Regenerative Medicine and Stem Cells Technologies 11-121522
6 · The paper itself

Abstract

backgroundIschemic stroke (IS) is one of the leading causes of death and long-term disability worldwide. In addition to physical deficits, stroke survivors also exhibit cognitive impairment. Reparative properties of mouse astrocyte extracellular vesicles (AS-EVs) have been proven in ischemic conditions. Here, the neuro-angiogenesis properties of melatonin (MT)-astrocyte EVs (MT-AS-EVs) were studied in IS mice.

methodsA total volume of 5 µl (~ 1 × 1011 particles) of MT-AS-EVs and AS-EVs was administered into the penumbra of the ischemic medial prefrontal cortex induced by photothrombosis. After 21 days, brain samples were taken, and protein levels of neuroangiogenesis (NeuN and vWF) and synaptogenesis (Homer, Synaptophysin, and Synapsin) were assessed using immunofluorescence (IF) staining and western blotting. The proinflammatory response was monitored by measuring TNF-α and TGF-β in brain samples. Behavioral tests were also conducted to evaluate cognitive performance.

resultsFrom TTC staining confirmed the efficiency of the present protocol for inducing IS in the target region. The injection of AS-EVs, especially MT-AS-EVs, reduced the infarcted area compared to IS mice. IF staining revealed induction of vWF + and NeuN + cells at the ischemic site in mice treated with AS-EVs and MT-AS-EVs, with a significant effect (p < 0.05). The protein levels of Homer, Synaptophysin, and Synapsin increased in the presence of MT-AS-EVs compared to the other experimental group. Additionally, MT-AS-EVs had the potential to attenuate the pro-inflammatory response by reducing TNF-α and TGF-β levels compared with IS mice (p < 0.05). It was noted that the improvement in behavioral parameters in the IS mice after injection of EVs, especially MT-AS-EVs (p < 0.05).

conclusionsAS-EVs are valid biological agents for inducing brain healing under IS conditions. Preconditioning with melatonin can enhance the reparative properties of AS-EVs, particularly in neuro-angiogenesis.

Indexed as

AngiogenesisAstrocytesBrain IschemiaExtracellular VesiclesMelatoninNeovascularization, PhysiologicPrefrontal CortexAnimalsMaleMiceMice, Inbred C57BLMelatoninAstrocytesExtracellular vesicleIschemic strokeMelatoninNeuro-angiogenesis

Identifiers

PMID41664147
PMCPMC12983613

What Socratic holds

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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 Socratic graph.