a-protocol-to-set-up-needle-free-connector-with-positive-displacement

A Protocol to Set Up Needle-Free Connector with Positive Displacement on Central Venous Catheter in Intensive Care Unit

Needle-free connectors were initially designed and promoted to avoid blood exposure for healthcare workers. Some recent data suggest that the latest ...

double-direct-injection-blood-into-cisterna-magna-as-model

Double Direct Injection of Blood into the Cisterna Magna as a Model of Subarachnoid Hemorrhage

Among strokes, subarachnoid hemorrhage (SAH) consecutive to the rupture of a cerebral arterial aneurysm represents 5-9% but is responsible for about 30% ...

Rouen University Hospital

University of Rouen Normandy, INSERM U1239, DC2N, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France

Rouen University Hospital, Rouen, France

Recent work has shown that benzodiazepines interact with the immune system and exhibit anti-inflammatory effects. By using in vitro models, researchers in several studies have shown that the peptidergic endogenous ligands of benzodiazepine receptors, named endozepines, are involved in the immune response. All endozepines identified so far derive from diazepam-binding inhibitor (DBI), which generates several biologically active fragments. The aim of the present study was to measure plasma levels of DBI-like immunoreactivity (DBI-LI) in a rat model of sepsis and in patients with systemic inflammation from septic or non-septic origin.

Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study.

The mechanisms involved in septic anorexia are mainly related to the secretion of inflammatory cytokines. The term endozepines designates a family of neuropeptides, including the octadecaneuropeptide (ODN), originally isolated as endogenous ligands of benzodiazepine receptors. Previous data showed that ODN, produced and released by astrocytes, is a potent anorexigenic peptide. We have studied the effect of sepsis by means of a model of cecal ligation and puncture (CLP) on the hypothalamic expression of endozepines (DBI mRNA and protein levels), as well as on the level of neuropeptides controlling energy homeostasis mRNAs: pro-opiomelanocortin, neuropeptide Y, and corticotropin-releasing hormone. In addition, we have investigated the effects of two inflammatory cytokines, TNF-α and IL-1β, on DBI mRNA levels in cultured rat astrocytes.

Increased Hypothalamic Levels of Endozepines, Endogenous Ligands of Benzodiazepine Receptors, in a Rat Model of Sepsis.

Noise, which is omnipresent in operating rooms and ICUs, may have a negative impact not only patients but also on the concentration of and communication between clinical staff.

Background noise lowers the performance of anaesthesiology residents' clinical reasoning when measured by script concordance: A randomised crossover volunteer study.

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.

Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage.

We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis.

Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model.

OBJECTIVECerebral vasospasm (VS) is a severe complication of aneurysmal subarachnoid hemorrhage (SAH). Urotensin II (UII) is a potent vasoactive peptide activating the urotensin (UT) receptor, potentially involved in brain vascular pathologies. The authors hypothesized that UII/UT system antagonism with the UT receptor antagonist/biased ligand urantide may be associated with post-SAH VS. The objectives of this study were 2-fold: 1) to leverage an experimental mouse model of SAH with VS in order to study the effect of urotensinergic system antagonism on neurological outcome, and 2) to investigate the association between plasma UII level and symptomatic VS after SAH in human patients.METHODSA mouse model of SAH was used to study the impacts of UII and the UT receptor antagonist/biased ligand urantide on VS and neurological outcome. Then a clinical study was conducted in the setting of a neurosurgical intensive care unit. Plasma UII levels were measured in SAH patients daily for 9 days, starting on the 1st day of hospitalization, and were compared with plasma UII levels in healthy volunteers.RESULTSIn the mouse model, urantide prevented VS as well as SAH-related fine motor coordination impairment. Seventeen patients with SAH and external ventricular drainage were included in the clinical study. The median plasma UII level was 43 pg/ml (IQR 14-80 pg/ml). There was no significant variation in the daily median plasma UII level (median value for the 17 patients) from day 0 to day 8. The median level of plasma UII during the 9 first days post-SAH was higher in patients with symptomatic VS than in patients without VS (77 pg/ml [IQR 33.5-111.5 pg/ml] vs 37 pg/ml [IQR 21-46 pg/ml], p < 0.05). Concerning daily measures of plasma UII levels in VS, non-VS patients, and healthy volunteers, we found a significant difference between SAH patients with VS (median 66 pg/ml [IQR 30-110 pg/ml]) and SAH patients without VS (27 pg/ml [IQR 15-46 pg/ml], p < 0.001) but no significant difference between VS patients and healthy volunteers (44 pg/ml [IQR 27-51 pg/ml]) or between non-VS patients and healthy volunteers.CONCLUSIONSThe results of this study suggest that UT receptor antagonism with urantide prevents VS and improves neurological outcome after SAH in mice and that an increase in plasma UII is associated with cerebral VS subsequent to SAH in humans. The causality link between circulating UII and VS after SAH remains to be established, but according to our data the UT receptor is a potential therapeutic target in SAH.

Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a potential therapeutic target.

ArticleTotal : 2	Year
Publication title Cited by 1	2019
Publication title Cited by 13	2020

Article	Year
Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study. Critical care (London, England)\| PubMed ID: 25407756	2014
Increased Hypothalamic Levels of Endozepines, Endogenous Ligands of Benzodiazepine Receptors, in a Rat Model of Sepsis. Shock (Augusta, Ga.)\| PubMed ID: 26796573	2016
Background noise lowers the performance of anaesthesiology residents' clinical reasoning when measured by script concordance: A randomised crossover volunteer study. European journal of anaesthesiology\| PubMed ID: 28394819	2017
Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage. Molecular neurobiology\| PubMed ID: 28455691	2018
Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model. Anesthesiology\| PubMed ID: 28542000	2017
Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a potential therapeutic target. Journal of neurosurgery\| PubMed ID: 30497195	2018

Antoine Lefevre-Scelles

Biography

JoVE Journal Publications

Other Publications