scholarly journals Circulating extracellular vesicles activate the pyroptosis pathway in the brain following ventilation-induced lung injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Laura Chavez ◽  
Julia Meguro ◽  
Shaoyi Chen ◽  
Vanessa Nunes de Paiva ◽  
Ronald Zambrano ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Lung Injury ◽  
Microglial Activation ◽  
Neonatal Rats ◽  
Neurodevelopmental Outcomes ◽  
Mechanically Ventilated ◽  
Caspase 1 ◽  
The Brain ◽  
Ventilation Induced Lung Injury

Abstract Background Mechanical ventilation of preterm newborns causes lung injury and is associated with poor neurodevelopmental outcomes. However, the mechanistic links between ventilation-induced lung injury (VILI) and brain injury is not well defined. Since circulating extracellular vesicles (EVs) are known to link distant organs by transferring their cargos, we hypothesized that EVs mediate inflammatory brain injury associated with VILI. Methods Neonatal rats were mechanically ventilated with low (10 mL/kg) or high (25 mL/kg) tidal volume for 1 h on post-natal day 7 followed by recovery for 2 weeks. Exosomes were isolated from the plasma of these rats and adoptively transferred into normal newborn rats. We assessed the effect of mechanical ventilation or exosome transfer on brain inflammation and activation of the pyroptosis pathway by western blot and histology. Results Injurious mechanical ventilation induced similar markers of inflammation and pyroptosis, such as increased IL-1β and activated caspase-1/gasdermin D (GSDMD) in both lung and brain, in addition to inducing microglial activation and cell death in the brain. Isolated EVs were enriched for the exosomal markers CD9 and CD81, suggesting enrichment for exosomes. EVs isolated from neonatal rats with VILI had increased caspase-1 but not GSDMD. Adoptive transfer of these EVs led to neuroinflammation with microglial activation and activation of caspase-1 and GSDMD in the brain similar to that observed in neonatal rats that were mechanically ventilated. Conclusions These findings suggest that circulating EVs can contribute to the brain injury and poor neurodevelopmental outcomes in preterm infants with VILI through activation of GSDMD.

scholarly journals The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Buqi Na ◽  
Hong Zhang ◽  
Guangfa Wang ◽  
Li Dai ◽  
Guoguang Xia
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Lung Injury ◽  
Rat Model ◽  
Central Control ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Lung Histology ◽  
Respiratory Centre ◽  
The Brain

Background and Objective. TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1’s functions and explored the mechanism using a rat model.Methods. Male Sprague-Dawley rats were randomized to three groups:(1)high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg;(2)low Vt (LVt): MV for four hours with Vt at 5 mL/kg;(3)basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity.Results. The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P=0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group.Conclusion. MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury.

scholarly journals Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thiago G. Bassi ◽  
Elizabeth C. Rohrs ◽  
Karl C. Fernandez ◽  
Marlena Ornowska ◽  
Michelle Nicholas ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Normal Lung ◽  
Preclinical Model ◽  
Negative Consequences ◽  
Mechanically Ventilated ◽  
Protective Mechanical Ventilation ◽  
Hippocampal Apoptosis ◽  
Lung Protective Mechanical Ventilation

AbstractMechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical ventilation, sedation and immobility, greater levels of hippocampal apoptosis and neuroinflammation were clearly observed in the mechanically ventilated group, in comparison to a never-ventilated group. Markers in the serum for astrocyte damage and neuronal damage were also higher in the mechanically ventilated group. Therefore, our study demonstrated that considerable hippocampal insult can be observed after 50 h of lung-protective mechanical ventilation, sedation and physical immobility.

scholarly journals Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 384-394 ◽  
Author(s):  
Judith Marín-Corral ◽  
Leticia Martínez-Caro ◽  
José A. Lorente ◽  
Marta de Paula ◽  
Lara Pijuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Adducts ◽  
Organ Injury ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cellular Inflammation ◽  
Cell Counts ◽  
Limb Muscles

Background High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury. Methods Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]). Results The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates. Conclusions Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.

Crosstalk between Microglia and Neurons in Neurotrauma: An Overview of the Underlying Mechanisms

2021 ◽  
Vol 19 ◽  
Author(s):  
Muhammad Ali Haidar ◽  
Stanley Ibeh ◽  
Zaynab Shakkour ◽  
Mohammad Amine Reslan ◽  
Judith Nwaiwu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Microglial Activation ◽  
Trauma Treatment ◽  
Cell Contact ◽  
Clear Understanding ◽  
Neuroinflammatory Response ◽  
Proinflammatory Responses ◽  
Underlying Mechanisms ◽  
The Brain ◽  
Cns Anomalies

: Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses are discussed. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely: traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment.

scholarly journals Fangchinoline ameliorates the expressions of angiogenic molecule in cerebral ischemia induced neuronal degeneration in neonatal rats

2018 ◽  
Vol 9 (1) ◽  
pp. 117-122
Author(s):  
Han Daicheng ◽  
Xia Shiwen ◽  
Zhu Huaping ◽  
Liu Yong ◽  
Zhou Qianqian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Neuronal Degeneration ◽  
Neuronal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neonatal Rats ◽  
Markers Of Oxidative Stress ◽  
The Brain

AbstractBackgroundPresent investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action.MethodologyCerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue.ResultsResult of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group.ConclusionIn conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

Does growth restriction increase the vulnerability to acute ventilation-induced brain injury in newborn lambs? Implications for future health and disease

2017 ◽  
Vol 8 (5) ◽  
pp. 556-565 ◽  
Author(s):  
B. J. Allison ◽  
S. B. Hooper ◽  
E. Coia ◽  
G. Jenkin ◽  
A. Malhotra ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Cell Damage ◽  
Inflammatory Marker ◽  
Neurovascular Unit ◽  
Early Brain Injury ◽  
Growth Restriction ◽  
Future Health ◽  
Fetal Sheep ◽  
The Brain

Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood–brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.

scholarly journals Neuromonitoring of delirium with quantitative pupillometry In sedated mechanically ventilated critically ill patients

2020 ◽  
Author(s):  
Eva Favre ◽  
Adriano Bernini ◽  
Paola Morelli ◽  
Jerôme Pasquier ◽  
John-Paul Miroz ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Potential Utility ◽  
Icu Patients ◽  
Mechanically Ventilated ◽  
Increased Risk ◽  
Infrared Pupillometry ◽  
Icu Delirium

Abstract Background. Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. Methods. This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 hours. Starting at day 3, automated infrared pupillometry – blinded to ICU caregivers – was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/sec). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. Results. A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/sec) at day 3, and at all additional time-points tested ( p <0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p =0.03). Conclusions. Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

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