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REVIEW article

Front. Med.

Sec. Intensive Care Medicine and Anesthesiology

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1655813

This article is part of the Research TopicLung Cross-talk in Acute Respiratory FailureView all articles

Organ crosstalk: Brain-lung interaction

Provisionally accepted
Luciana  MasciaLuciana Mascia1*Rosanna  D'alboRosanna D'albo2Irene  CavalliIrene Cavalli3Luca  GiaccariLuca Giaccari4,5Maria  Della GiovampaolaMaria Della Giovampaola3Beatrice  DonatiBeatrice Donati6
  • 1University of Salento, Lecce, Italy
  • 2Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
  • 3Anesthesiology and General Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  • 4Anestesia e Rianimazione - Ospedale Vito Fazzi, Lecce, Italy
  • 5Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica - Università della Campania “L. Vanvitelli”, Napoli, Italy
  • 6Department of Anesthesiology, University Medical Center Göttingen, Goettingen, Germany

The final, formatted version of the article will be published soon.

The interaction between the brain and the lungs is bidirectional: ICU patients with acute brain injury develop pulmonary complications, while ARDS patients frequently manifest neurological sequelae.Research is indeed focusing on both aspects of this cross-talk.On one side, ARDS survivors experience poor neurological outcomes both in the short and long term, with high incidence of delirium and post-discharge neurocognitive impairment. The underlying mechanisms have been investigated either in the pre-clinical and in the clinical field. Ventilator associated brain injury is the new recent term used to indicate the brain damage consequent to mechanical ventilation and leading to neuroinflammation and increased brain cells apoptosis. Moreover, prolonged hypoxia, deep sedation, loss of cerebral autoregulation and complications from vv-ECMO during ARDS are potentially sources of brain damage.On the other side, pulmonary complications in patients with acute brain injury follow a double-hit model, recently implemented in a triple-hit hypothesis. According to this theory, the primary brain injury leads to sympathetic hyperactivity, with inflammation and oxidative stress. Thus, the lungs become more vulnerable to develop complications such as neurogenic pulmonary edema and pneumonia. Finally, immune dysregulation and microbiome alterations due to brain-lung cross-talk lead to the worsening of lung injury. In this context, mechanical ventilation strategies aiming to guarantee adequate gas exchange and brain oxygen delivery are essential to prevent this phenomenon cascade. This review purpose is to examine the mechanisms behind brain-lung cross talk, starting from pathophysiological mechanisms, in order to suggest potential new research and therapeutic approaches.

Keywords: Acute brain injury, ARDS, brain-lung cross talk, ventilator associated brain injury, mechanical ventilation, Neurogenic pulmonary edema

Received: 28 Jun 2025; Accepted: 06 Aug 2025.

Copyright: © 2025 Mascia, D'albo, Cavalli, Giaccari, Della Giovampaola and Donati. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Luciana Mascia, University of Salento, Lecce, Italy

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