IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury

Sparrow, Nicklaus A.; Anwar, Faizan; Covarrubias, Ambart E.; Rajput, Padmesh S.; Rashid, Mohammad H.; Nisson, Peyton L.; Gezalian, Michael; Toossi, Shahed; Ayodele, Maranatha; Karumanchi, S. Ananth; Ely, E. Wesley; Lahiri, Shouri

doi:10.1165/rcmb.2021-0072oc

Cited by 30 publications

(31 citation statements)

References 42 publications

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“…This proposal is further supported by a recent experimental study of Sparrow and colleagues, who reported that acute lung injury due to mechanical ventilation induced reversible neuronal injury and inflammation in the frontal cortex and hippocampus of mechanically ventilated mice. Importantly, inhibition of IL-6 signalling reduced frontal and hippocampal apoptosis [ 75 ].…”

Section: Pathophysiology Of Ards-associated Brain Dysfunctionmentioning

confidence: 99%

ARDS associated acute brain injury: from the lung to the brain

Ziaka¹,

Exadaktylos

2022

Eur J Med Res

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A complex interrelation between lung and brain in patients with acute lung injury (ALI) has been established by experimental and clinical studies during the last decades. Although, acute brain injury represents one of the most common insufficiencies in patients with ALI and acute respiratory distress syndrome (ARDS), the underlying pathophysiology of the observed crosstalk remains poorly understood due to its complexity. Specifically, it involves numerous pathophysiological parameters such as hypoxemia, neurological adverse events of lung protective ventilation, hypotension, disruption of the BBB, and neuroinflammation in such a manner that the brain of ARDS patients—especially hippocampus—becomes very vulnerable to develop secondary lung-mediated acute brain injury. A protective ventilator strategy could reduce or even minimize further systemic release of inflammatory mediators and thus maintain brain homeostasis. On the other hand, mechanical ventilation with low tidal volumes may lead to self-inflicted lung injury, hypercapnia and subsequent cerebral vasodilatation, increased cerebral blood flow, and intracranial hypertension. Therefore, by describing the pathophysiology of ARDS-associated acute brain injury we aim to highlight and discuss the possible influence of mechanical ventilation on ALI-associated acute brain injury.

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Section: Pathophysiology Of Ards-associated Brain Dysfunctionmentioning

confidence: 99%

ARDS associated acute brain injury: from the lung to the brain

Ziaka¹,

Exadaktylos

2022

Eur J Med Res

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“…The increase in systemic IL-6 levels may have reflected a buffering role for immune monitoring given its dual role in pro-inflammatory and anti-inflammatory signalling ( Turner et al, 2014 ). Indeed, a recent study in overventilated mice suggested a capacity for systemic IL-6 signalling to cross the blood-brain barrier (BBB) and induce neuronal injury ( Sparrow et al, 2021 ). Furthermore, previous studies in preterm fetal sheep have demonstrated a strong association between increased circulating IL-6 levels and neuroinflammation and injury ( Galinsky et al, 2020a ; Galinsky et al, 2020b ).…”

Section: Discussionmentioning

confidence: 99%

Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs

Chan

Tran²,

Papagianis³

et al. 2022

Front. Physiol.

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Initiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to assess the role of the inflammatory and haemodynamic pathway on ventilation-induced brain injury (VIBI) in the preterm lamb. Fetal lambs (125 ± 1 day gestation) were exteriorised, instrumented and ventilated with a high tidal-volume (VT) injurious strategy for 15 min either with placental circulation intact to induce the inflammatory pathway only (INJINF; n = 7) or umbilical cord occluded to induce both the inflammatory and haemodynamic pathways (INJINF+HAE; n = 7). Sham controls were exteriorised but not ventilated (SHAM; n = 5) while unoperated controls (UNOP; n = 7) did not undergo fetal instrumentation. Fetuses were returned in utero following intervention and the ewe allowed to recover. Arterial blood gases and plasma were sampled periodically. Twenty-four hours following intervention, lambs were delivered and maintained on non-injurious ventilation for ∼40 min then brains were collected post-mortem for immunohistochemistry and RT-qPCR to assess inflammation, vascular pathology and cell death within white matter regions. Compared to INJINF lambs, INJINF+HAE lambs achieved a consistently higher VT during injurious ventilation and carotid blood flow was significantly lower than baseline by the end of ventilation. Throughout the 24 h recovery period, systemic arterial IL-6 levels of INJINF+HAE lambs were significantly higher than SHAM while there was no difference between INJINF and SHAM animals. At 24 h, mRNA expression levels of pro-inflammatory cytokines, tight junction proteins, markers of cell death, and histological injury indices of gliosis, blood vessel protein extravasation, oligodendrocyte injury and cell death were not different between groups. Injurious ventilation, irrespective of strategy, did not increase brain inflammation or injury 24 h later when compared to control animals. However, the haemodynamic pathway did influence carotid blood flow adaptations during injurious ventilation and increased systemic arterial IL-6 that may underlie long-term pathology. Future studies are required to further characterise the pathways and their long-term effects on VIBI.

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“…In a recent study using a mouse model, the neurological damage in mice with lung damage could be reduced by suppressing levels of IL-6 [ 164 ]. Although only a few studies have reported on the relationship between breathing exercises and IL-6 in patients with stroke, several studies have been conducted on different sets of participants.…”

Section: Associations Between the Factors Influencing Cognitive Decli...mentioning

confidence: 99%

Breathing Exercises for Improving Cognitive Function in Patients with Stroke

Kang

Yook

2022

JCM

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Patients with stroke may experience a certain degree of cognitive decline during the period of recovery, and a considerable number of such patients have been reported to show permanent cognitive damage. Therefore, the period of recovery and rehabilitation following stroke is critical for rapid cognitive functional improvements. As dysfunctional breathing has been reported as one of the factors affecting the quality of life post stroke, a number of studies have focused on the need for improving the breathing function in these patients. Numerous breathing exercises have been reported to enhance the respiratory, pulmonary, cognitive, and psychological functions. However, scientific evidence on the underlying mechanisms by which these exercises improve cognitive function is scattered at best. Therefore, it has been difficult to establish a protocol of breathing exercises for patients with stroke. In this review, we summarize the psychological, vascular, sleep-related, and biochemical factors influencing cognition in patients and highlight the need for breathing exercises based on existing studies. Breathing exercises are expected to contribute to improvements in cognitive function in stroke based on a diverse array of supporting evidence. With relevant follow-up studies, a protocol of breathing exercises can be developed for improving the cognitive function in patients with stroke.

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IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury

Cited by 30 publications

References 42 publications

ARDS associated acute brain injury: from the lung to the brain

ARDS associated acute brain injury: from the lung to the brain

Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs

Breathing Exercises for Improving Cognitive Function in Patients with Stroke

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