ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2025
Extracellular Vesicles from Peripheral Blood Mononuclear Cells of Hyperammonemic Rats Induce Neuroinflammation in Hippocampus, Impairing Memory and Learning in Normal Rats.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
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.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE), with mild cognitive impairment. Studies in patients and animal models show that MHE is triggered by a shift in peripheral inflammation. Peripheral extracellular vesicles (EVs) seem to mediate transmission of deleterious effects to the brain. However, it is not known which cell types produce the pathological EVs. The aim of this study was to assess if EVs released from cultured peripheral blood mononuclear cells from hyperammonemic rats with MHE (HA-PBMC-EVs) transmit pathological signals to the brain when injected into normal rats and to analyze the underlying mechanisms. We found that HA-PBMC-EVs induce neuroinflammation in hippocampus and cognitive impairment in normal rats, indicating that hyperammonemia alters the EVs released by PBMCs, which mediate cognitive impairment induction. We also identified underlying mechanisms: HA-PBMC-EVs enhance membrane expression and activation of TNFR1 and of S1PR2, increasing IL-1β and phosphorylation of Src, which increases CCL2 and BDNF content and membrane expression of the GLUN2B subunit of the NMDA receptor. BDNF activates TrkB, leading to phosphorylation and activation of Akt, which further increases BDNF. The increased activation of GLUN2B alters membrane expression of GluA1 and GluA2 subunits of AMPA receptors, which would be responsible for the induction of cognitive impairment. Moreover, blocking TNFα in the HA-PBMC-EVs prevents the activation of the TNFα-TNFR1-S1PR2-IL-1β-Src-BDNF-TrkB pathway and the changes in membrane expression of NMDA and AMPA receptors. EVs from PBMC may be therefore a therapeutic target on which to act to reverse cognitive impairment in patients with MHE.
Indexed as
Identifiers
40481977What OpenQuestion holds
Registered trials
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.