Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

Dąbrowski, Wojciech; Siwicka-Gieroba, Dorota; Robba, Chiara; Bielacz, Magdalena; Sołek-Pastuszka, Joanna; Kotfis, Katarzyna; Bohatyrewicz, Romuald; Jaroszyński, Andrzej; Malbrain, Manu L N G; Badenes, Rafael

doi:10.3390/jcm10184141

Cited by 12 publications

(6 citation statements)

References 90 publications

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“…In humans, cerebral edema resulting from brain injury is frequently treated with hyperosmotic therapy to relieve inter cranial hypertension [32]. However, recent evidence suggests that elevating plasma osmolality can also lead to increased QTc and a higher risk of cardiac arrhythmias [33,34]. We therefore sought to determine what effect osmotic perturbations had on zebrafish ECG patterns.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the adult zebrafish electrocardiogram

Arel

Rolland

Thireau

et al. 2022

Preprint

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Background: The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis, is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. Methods: ECGs were recorded from adult zebrafish hearts in 3 different configurations (unexposed heart, exposed heart and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. Results: We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T-wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P-waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate. Conclusions: The exposed heart configuration appears to be the most reliable technique to record ECGs in adult zebrafish. In this configuration, the QT-RR relationship, an important parameter in cardiac toxicity evaluation, can be determined using the Holzgrefe correction.

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Section: Resultsmentioning

confidence: 99%

Characterization of the adult zebrafish electrocardiogram

Arel

Rolland

Thireau

et al. 2022

Preprint

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“…In summary, the neuroendocrine pathway, including the central nervous autonomous system and the endocrine system, and the inflammatory and immune responses play a major role in its development [ 5 , 6 ]. Patient-, trauma-, iatrogenic- or treatment-related factors may contribute [ 5 , 6 , 7 ]. Indeed, the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) showed that an AKI incidence of 12% of cases in a sample of 1262 TBI patients was associated with patients’ previous conditions (renal history and insulin-dependent diabetes), trauma (pupillary reactivity) and treatments received (osmotic therapy and natremia ≥ 150 mmol/L in the initial 3 days after injury) [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Iatrogenic factors, including exposure to radiocontrast agents, nephrotoxic antibiotics and anti-inflammatory agents [ 6 ], must also be considered in brain-injured patients. The treatment of intracranial hypertension may also contribute to the development of AKI [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Traumatic Brain Injury and Acute Kidney Injury—Outcomes and Associated Risk Factors

Barea‐Mendoza

Chico‐Fernández

Quintana-Díaz

et al. 2022

JCM

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Our objective was to analyze the contribution of acute kidney injury (AKI) to the mortality of isolated TBI patients and its associated risk factors. Observational, prospective and multicenter registry (RETRAUCI) methods were used, from March 2015 to December 2019. Isolated TBI was defined as abbreviated injury scale (AIS) ≥ 3 head with no additional score ≥ 3. A comparison of groups was conducted using the Wilcoxon test, chi-square test or Fisher’s exact test, as appropriate. A multiple logistic regression analysis was conducted to analyze associated risk factors in the development of AKI. For the result, overall, 2964 (30.2%) had AIS head ≥ 3 with no other area with AIS ≥ 3. The mean age was 54.7 (SD 19.5) years, 76% were men, and the ground-level falls was 49.1%. The mean ISS was 18.4 (SD 8). The in-hospital mortality was 22.2%. Up to 310 patients (10.6%) developed AKI, which was associated with increased mortality (39% vs. 17%, adjusted OR 2.2). Associated risk factors (odds ratio (OR) (95% confidence interval)) were age (OR 1.02 (1.01–1.02)), hemodynamic instability (OR 2.87 to OR 5.83 (1.79–13.1)), rhabdomyolysis (OR 2.94 (1.69–5.11)), trauma-associated coagulopathy (OR 1.67 (1.05–2.66)) and transfusion of packed red-blood-cell concentrates (OR 1.76 (1.12–2.76)). In conclusion, AKI occurred in 10.6% of isolated TBI patients and was associated with increased mortality.

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“…Current interventions include the use of drugs such as mannitol or bradykinin analog (Cereport/RMP7) to induce disruption of barrier function. Hypertonic mannitol, reduces tight junction integrity through endothelial cell contraction ( Dabrowski et al, 2021 ), but its limitation is that it may cause seizures ( Marchi et al, 2007 ). Cereport/RMP-7 has shown some potential to transiently increase BBB permeability ( Borlongan and Emerich, 2003 ) and has shown some efficacy in animal models for the treatment of CNS pathology, but has not yielded satisfactory results in clinical trials ( Prados et al, 2003 ).…”

Section: Prospects For Improving Drug Delivery Within the Cnsmentioning

confidence: 99%

Purinergic signaling: A gatekeeper of blood-brain barrier permeation

Wang

Zhu²,

Wang³

et al. 2023

Front. Pharmacol.

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This review outlined evidence that purinergic signaling is involved in the modulation of blood-brain barrier (BBB) permeability. The functional and structural integrity of the BBB is critical for maintaining the homeostasis of the brain microenvironment. BBB integrity is maintained primarily by endothelial cells and basement membrane but also be regulated by pericytes, neurons, astrocytes, microglia and oligodendrocytes. In this review, we summarized the purinergic receptors and nucleotidases expressed on BBB cells and focused on the regulation of BBB permeability by purinergic signaling. The permeability of BBB is regulated by a series of purinergic receptors classified as P2Y1, P2Y4, P2Y12, P2X4, P2X7, A1, A2A, A2B, and A3, which serve as targets for endogenous ATP, ADP, or adenosine. P2Y1 and P2Y4 antagonists could attenuate BBB damage. In contrast, P2Y12-mediated chemotaxis of microglial cell processes is necessary for rapid closure of the BBB after BBB breakdown. Antagonists of P2X4 and P2X7 inhibit the activation of these receptors, reduce the release of interleukin-1 beta (IL-1β), and promote the function of BBB closure. In addition, the CD39/CD73 nucleotidase axis participates in extracellular adenosine metabolism and promotes BBB permeability through A1 and A2A on BBB cells. Furthermore, A2B and A3 receptor agonists protect BBB integrity. Thus, the regulation of the BBB by purinergic signaling is complex and affects the opening and closing of the BBB through different pathways. Appropriate selective agonists/antagonists of purinergic receptors and corresponding enzyme inhibitors could modulate the permeability of the BBB, effectively delivering therapeutic drugs/cells to the central nervous system (CNS) or limiting the entry of inflammatory immune cells into the brain and re-establishing CNS homeostasis.

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Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

Cited by 12 publications

References 90 publications

Characterization of the adult zebrafish electrocardiogram

Characterization of the adult zebrafish electrocardiogram

Traumatic Brain Injury and Acute Kidney Injury—Outcomes and Associated Risk Factors

Purinergic signaling: A gatekeeper of blood-brain barrier permeation

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