ArticleCritical care medicine2019
Lung Purinoceptor Activation Triggers Ventilator-Induced Brain Injury.
Article in Critical care medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Systematic review of cognitive impairment and brain insult after mechanical ventilation.Critical care (London, England) · 2021Pooled it
- Mechanical Ventilation-Associated Changes in Hippocampal Electroencephalogram: A Cross-Species Study in Humans and Rats.CNS neuroscience & therapeutics · 2026Article
- Sedation as an Immunomodulator of Inflammatory Responses in the Lung-Brain Axis of ARDS.International journal of molecular sciences · 2026Review
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Little Big Issues in Brain-Lung Crosstalk.American journal of respiratory and critical care medicine · 2025Article
- Decoding mechanisms and protein markers in lung-brain axis.Respiratory research · 2025Review
- Organ crosstalk: brain-lung interaction.Frontiers in medicine · 2025Review
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: NHLBI Workshop Report.American journal of respiratory and critical care medicine · 2024Article
- Ventilator-associated Brain Injury: A New Priority for Research in Mechanical Ventilation.American journal of respiratory and critical care medicine · 2024Article
- Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke.Neural regeneration research · 2024Review
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
- Therapeutic role of gut microbiota in lung injury-related cognitive impairment.Frontiers in nutrition · 2024Review
- Pressure-support compared with pressure-controlled ventilation mitigates lung and brain injury in experimental acute ischemic stroke in rats.Intensive care medicine experimental · 2023Article
- Future directions in ventilator-induced lung injury associated cognitive impairment: a new sight.Frontiers in physiology · 2023Review
- Diaphragm Neurostimulation Mitigates Ventilation-Associated Brain Injury in a Preclinical Acute Respiratory Distress Syndrome Model.Critical care explorations · 2022Article
- ARDS associated acute brain injury: from the lung to the brain.European journal of medical research · 2022Review
- Pulmonary complications and respiratory management in neurocritical care: a narrative review.Chinese medical journal · 2022Review
- Mechanical ventilation induces lung and brain injury through ATP production, P2Y1 receptor activation and dopamine release.Bioengineered · 2022Review
- Transvenous Diaphragm Neurostimulation Mitigates Ventilation-associated Brain Injury.American journal of respiratory and critical care medicine · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesMechanical ventilation can cause ventilator-induced brain injury via afferent vagal signaling and hippocampal neurotransmitter imbalances. The triggering mechanisms for vagal signaling during mechanical ventilation are unknown. The objective of this study was to assess whether pulmonary transient receptor potential vanilloid type-4 (TRPV4) mechanoreceptors and vagal afferent purinergic receptors (P2X) act as triggers of ventilator-induced brain injury.
designControlled, human in vitro and ex vivo studies, as well as murine in vivo laboratory studies.
settingResearch laboratory. SUBJECTS: Wild-type, TRPV4-deficient C57BL/6J mice, 8-10 weeks old. Human postmortem lung tissue and human lung epithelial cell line BEAS-2B.
interventionMice subjected to mechanical ventilation were studied using functional MRI to assess hippocampal activity. The effects of lidocaine (a nonselective ion-channel inhibitor), P2X-purinoceptor antagonist (iso-PPADS), or genetic TRPV4 deficiency on hippocampal dopamine-dependent pro-apoptotic signaling were studied in mechanically ventilated mice. Human lung epithelial cells (BEAS-2B) were used to study the effects of mechanical stretch on TRPV4 and P2X expression and activation. TRPV4 levels were measured in postmortem lung tissue from ventilated and nonventilated patients. MEASUREMENTS AND MAIN
resultsHippocampus functional MRI analysis revealed considerable changes in response to the increase in tidal volume during mechanical ventilation. Intratracheal lidocaine, iso-PPADS, and TRPV4 genetic deficiency protected mice against ventilationinduced hippocampal pro-apoptotic signaling. Mechanical stretch in both, BEAS-2B cells and ventilated wild-type mice, resulted in TRPV4 activation and reduced Trpv4 and P2x expression. Intratracheal replenishment of adenosine triphosphate in Trpv4 mice abrogated the protective effect of TRPV4 deficiency. Autopsy lung tissue from ventilated patients showed decreased lung TRPV4 levels compared with nonventilated
conclusions: TRPV4 mechanosensors and purinergic receptors are involved in the mechanisms of ventilator-induced brain injury. Inhibition of this neural signaling, either using nonspecific or specific inhibitors targeting the TRPV4/adenosine triphosphate/P2X signaling axis, may represent a novel strategy to prevent or treat ventilator-induced brain injury.
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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.