ArticleJournal of neuroinflammation2026
PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.
Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundNeonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of neurological deficits and death in neonates. In HIBD, the death of endothelial cells and disruption of the blood-brain barrier (BBB) are closely related to the severity of brain damage and long-term clinical outcomes. There is increasing evidence that a glycolytic enzyme, pyruvate kinase M2 (PKM2), is essential for managing metabolic processes in endothelial cells, but its role (and underlying molecular mechanism) in hypoxic-ischemic (HI)-associated endothelial cell metabolism, cell survival, and BBB function remains unknown.
methodsWe established an in vivo HI-induced brain injury rat model and an in vitro model in which human cerebral microvascular endothelial cells (hCMECs) underwent oxygen-glucose deprivation (OGD). Infarct volume was measured and neurobehavioral tests were conducted to assess brain damage, and Evans blue extravasation and FITC-dextran were used to evaluate the BBB. RNA sequencing, qRT-PCR, western blotting, and immunofluorescence labeling were conducted to identify the molecular mechanisms underlying HIBD.
resultsPKM2 expression was upregulated in the brains of HIBD rats and in OGD-treated hCMECs. The inhibition of PKM2 greatly upregulated the expression of pyroptosis-associated proteins, including NLRP3, cleaved caspase-1, GSDMD, IL-1β, and IL-18. In contrast, the activation of PKM2 preserved junctional proteins and maintained the integrity of the BBB, which together improved functional recovery in HIBD rats. Mechanistically, preconditioning of PKM2 contributed to lactate-mediated cellular defense mechanisms, including the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and thioredoxin (TRX), and to the downregulation of thioredoxin-interacting protein (TXNIP) via a modest increase in reactive oxygen species.
conclusionsOur analyses provide compelling evidence that PKM2 preconditioning attenuates endothelial cell pyroptosis and BBB disruption in neonatal HIBD by causing oxidative stress resistance and activating the NRF2/TRX/TXNIP pathway. Therefore, PKM2 represents a promising pharmacological target for treating HIBD.
Indexed as
Identifiers
What Socratic 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 Socratic graph.