Evidence map›Paper›PMID 40976402›Full record

ReviewBrain, behavior, and immunity2025

Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.

Namdev S Togre, Priyanka S Bhoj, Naveen Mekala, Rebecca Hancock, Jayshil Trivedi, Yuri Persidsky

Abstract readReview
In one paragraph

Review in Brain, behavior, and immunity, 2025. 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. Article
  4. Review
  5. Article
  6. Article
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

6 authors.

Namdev S TogreDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: namdev.togre@temple.edu.
Priyanka S BhojDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Naveen MekalaDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Rebecca HancockDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Jayshil TrivediDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Yuri PersidskyDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: yuri.persidsky@tuhs.temple.edu.

Funding

HIV-induced neuroinflammation associated with opioid abuse and tobacco smokeR01DA040619 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI PERSIDSKY, YURI, ROGERS, THOMAS J · 2016 to 2020
$3.2M
The role of cannabinoids in the regulation of the blood brain barrier in the context of NeuroHIV and anti-retroviral therapyR01DA052970 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI PERSIDSKY, YURI, RAMIREZ, SERVIO HEYBERT · 2021 to 2025
$3.0M
Injury of blood brain and alveolar-endothelial barriers caused by alcohol and electronic cigarettes via purinergic receptor signalingR01AA030841 · NIAAA · TEMPLE UNIV OF THE COMMONWEALTH · PI Yuri Persidsky · 2023 to 2026
$2.4M
NIAAA NIH HHS R01 AA030841NIDA NIH HHS R01 DA040619NIDA NIH HHS R01 DA052970
6 · The paper itself

Abstract

Chronic alcohol consumption is a major risk factor for neuroinflammation and cognitive decline, yet the molecular underpinnings connecting peripheral alcohol-induced injury to central nervous system (CNS) dysfunction remain poorly defined. Emerging evidence implicates purinergic P2X7 receptor (P2X7R) signaling and extracellular vesicles (EVs) as key mediators in peripheral-central communication. Ethanol exposure promotes oxidative stress, mitochondrial dysfunction, and blood-brain barrier (BBB) disruption, leading to sustained microglial activation and neuronal injury. Concurrently, alcohol-induced damage in the gut, liver, and lung, triggers systemic inflammation and EV release. These EVs, enriched in proinflammatory cytokines, miRNAs, mitochondrial DNA, and other DAMPs, can cross the compromised BBB and engage innate immune receptors, such as TLR4 and P2X7R, on glial cells, amplifying neuroimmune responses. In this review, we integrated recent findings on EV biogenesis, P2X7R signaling, and neurovascular dysfunction in the context of alcohol use disorder. We proposed a mechanistic model in which ethanol-triggered P2X7R activation drives EV release, turning these vesicles into inflammatory couriers that carry peripheral injury signals to the brain. We emphasize EV cargo as promising biomarkers of alcohol-related neurodegeneration and explore emerging therapies that target EV pathways or P2X7R to curb alcohol-induced CNS damage.

Indexed as

Blood-Brain BarrierEthanolExtracellular VesiclesReceptors, Purinergic P2X7AlcoholismAnimalsHumansInflammationMicrogliaNeuroimmunomodulationNeuroinflammatory DiseasesSignal TransductionEthanolReceptors, Purinergic P2X7Alcohol use disorderBiomarkersBlood–brain barrierExtracellular vesiclesInflammationNeuroinflammationOxidative stressP2X7 receptor

Identifiers

PMID40976402
PMCPMC12676963

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.