Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 26, 2025

Abstract Acute respiratory distress syndrome (ARDS) is a clinical of acute hypoxic failure caused by diffuse lung inflammation and edema. ARDS can be precipitated intrapulmonary factors or extrapulmonary factors, which lead to severe hypoxemia. Patients suffering from have high mortality rates, including 28‐day rate 34.8% an overall in‐hospital 40.0%. The pathophysiology complex involves the activation dysregulation multiple overlapping interacting pathways systemic coagulation, system, circulatory immune system. In general, treatment inflammatory injuries coordinated process that downregulation proinflammatory upregulation anti‐inflammatory pathways. Given complexity underlying disease, needs tailored problem. Hence, we discuss pathogenesis methods affected organs, 2019 coronavirus disease (COVID‐19)‐related pneumonia, drowning, trauma, blood transfusion, pancreatitis, sepsis. This review intended provide new perspective concerning offer novel insight into future therapeutic interventions.

Language: Английский

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Fingolimod Suppresses NLRP3 Inflammasome Activation and Alleviates Oxidative Stress in Traumatic Brain Injury-Induced Acute Lung Injury

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2229 - 2245

Published: Feb. 1, 2025

Acute lung injury (ALI) is a serious yet common complication in patients with traumatic brain (TBI), often associated poor prognosis. The development of TBI-induced ALI closely excessive oxidative stress and NLRP3 inflammasome activation. Fingolimod, an immunomodulatory agent, has been reported to attenuate inflammatory responses, restore blood-brain barrier integrity, reduce cerebral edema, mitigate neurological deficits. This study aimed investigate the mechanistic role activation evaluate therapeutic potential fingolimod targeting this pathway. A rat TBI model was established using classical free-fall method, animals were treated (0.5 or 1 mg/kg) daily for three days. rats presented clear signs histopathological pulmonary damage, increase permeability capillaries lung, edema that coincided significantly increased NLRP3, caspase-1, ASC expression tissue samples. overexpression machinery resulted release IL-1β. Fingolimod treatment, however, reversed all these effects such it suppressed activity normalized levels IL-1β, leading alleviation inflammation. In line results, LPS nigericin (NLRP3 agonist)-treated NR8383 cells exhibited reductions reactive oxygen species production These findings suggest are key mediators ALI. exerts protective against condition by inhibiting activation, highlighting its as agent TBI-associated complications.

Language: Английский

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Decoding mechanisms and protein markers in lung-brain axis

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 19, 2025

The lung-brain axis represents a complex bidirectional communication network that is pivotal in the crosstalk between respiratory and neurological functions. This review summarizes current understanding of mechanisms protein markers mediate effects lung diseases on brain health. In this review, we explore linking injury to neurocognitive impairments, focusing neural pathways, immune regulation inflammatory responses, microorganism hypoxemia. Specifically, highlight role vagus nerve modulating central nervous system response pulmonary stimuli; Additionally, regulatory function underscored, with evidence suggesting lung-derived mediators can traverse blood-brain barrier, induce neuroinflammation cognitive decline; Furthermore, discuss potential microbiota influence through microbial translocation activation; Finally, impact hypoxemia examined, findings indicating it exacerbate cerebral via oxidative stress impaired perfusion. Moreover, analyze how conditions, such as pneumonia, ALI/ARDS, asthma, contribute dysfunction. Prolonged mechanical ventilation also impairment. Conversely, (e.g., stroke, traumatic injury) lead acute complications. addition, TLR4, ACE2, A-SAA, HMGB1, TREM2 are crucial correlate disease severity. We emerging therapeutic strategies targeting axis, including immunomodulation microbiome engineering. Overall, interplay for developing integrated treatment improving patient outcomes. Further research needed elucidate molecular foster interdisciplinary collaboration.

Language: Английский

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Models of traumatic brain injury: modern approaches, classification, and research perspectives

Pediatrician (St Petersburg), Journal Year: 2024, Volume and Issue: 15(6), P. 49 - 61

Published: Dec. 19, 2024

Traumatic brain injury represents one of the most complex biomedical challenges, affecting millions people worldwide each year. Various experimental and theoretical models are used to understand pathophysiology traumatic develop effective therapeutic strategies. This review focuses on three main groups models: (in silico), cellular vitro), animal vivo). Theoretical based mathematical approaches computer simulations analyze mechanical injuries, edema processes, ischemia, neuroinflammation. In silico provide high precision reproducibility but require proper validation with biological data. Cellular include cultivation neurons, astrocytes, microglia, organoids, which subjected or chemical factors that mimic injury. These systems allow researchers study molecular mechanisms such as apoptosis, neuroinflammation, regeneration. However, in vitro limited by absence a systemic response characteristic an entire organism. Animal considered “gold standard” for studying involve direct impacts brains animals (e.g., mice, rats, pigs), enabling reproduction clinical aspects trauma, including behavioral pathophysiological changes. Despite their physiological relevance, vivo face ethical limitations challenges extrapolating results humans. article provides overview modern modeling, classification, characteristics, advantages, limitations. The data presented may serve foundation developing more treatment rehabilitation strategies patients.

Language: Английский

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