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Abella 2023 Abstract IOC160

From Bioblast
Abella P, Valez V, Vaamonde L, Blasina F, Rodriguez-Rey M (2023) Severe acute neonatal hypoxia: mitochondrial dysfunction at an animal model and the role of nitric oxide. Mitochondr Physiol Network 28.01.

Link: IOC160

Abella Pilar, Valez Valeria, Vaamonde Lucia, Blasina Fernanda, Rodriguez-Rey Marianela (2023)

Event: IOC160

Hypoxic-ischemic events due to intrapartum complications are the second leading cause of neonatal mortality and initiate an acute brain disorder known as hypoxic-ischemic encephalopathy (HIE). In HIE, the brain undergoes primary and secondary mitochondrial energy failure phases, between there is a latent phase where partial neuronal recovery is observed. At neuronal level, the entry of calcium due to hypoxia-ischemia, activates neuronal nitric oxide synthase (nNOS) resulting in the production of nitric oxide (•NO). This leads to accumulation of reactive oxygen and nitrogen species, causing mitochondrial damage. Mitochondrial dysfunction exacerbates the injury caused by hypoxia. Pharmacological treatments targeting mitochondria or inhibiting •NO production plays a key role in improving mitochondrial function, consequently, neuroprotection. 2-iminobiotin (2IB) inhibits nNOS and is currently in study as a neuroprotective agent.

The aim of this study is to investigate the effect of hypoxia on the developing brain in a neonatal piglet model and the pharmacological neuroprotection provided by 2IB as a modulator of neuronal •NO production.

For this purpose, a 24-48-hour-old newborn piglet (Sus scrofa domestica) model is used. The animals are anesthetized and placed on mechanical ventilatory support with FiO2 of 0.21 (normoxia). Throughout the experiment, they are continuously monitored using pulse oximetry and regional cerebral near-infrared spectroscopy (NIRS), invasive blood pressure measurement, integrated amplitude electroencephalogram (aEEG), central temperature, and serial blood gasses analysis. Hypoxia is induced by obstructing the endotracheal tube for 4 minutes, repeating this procedure 3 times every 30 minutes. Between each hypoxia, re ventilation with FiO2. 0.21 The administration of 2IB is done immediately after hypoxia (intravenous 0.2 mg/kg of 2IB). After 4 hours, the animal is sacrificed. Brain biopsies are taken to measure mitochondrial function. Mitochondrial respiration is measured in brain biopsies using an Oroboros Oxygraph at 37°C.

At present, this project is under development. Some experimental procedures have been already done. During hypoxia it was observed hemodynamic affectation shown by bradycardia, increased blood pressure, and decreased oxygen saturation and regional cerebral oxygen saturation, recovering between each hypoxia. On the aEEG, a voltage decrease is observed during hypoxia with subsequent recovery. In blood gasses analysis it is observed a sustained increase in lactate without recovery between hypoxia. Regarding mitochondrial function, a decrease in all respiratory indices was observed in the hypoxia group compared to the control group. We observe significant differences on maximum respiration, reserve capacity and non-mitochondrial consumption. Until now we do not have 2IB results.

Bioblast editor: Plangger M O2k-Network Lab: UY Montevideo Rodriguez-Rey M

Labels: MiParea: Respiration 

Stress:Oxidative stress;RONS, Hypoxia  Organism: Pig  Tissue;cell: Nervous system 

HRR: Oxygraph-2k 

Affiliations and support

Abella Pilar1, Valez Valeria2, Vaamonde Lucia1, Blasina Fernanda1, Rodriguez-Rey Marianela1,2
  1. Hospital de Clínicas University Hospital, School of Medicine, University of the Uruguayan Republic, UDELAR, Uruguay
  2. Centro de Investigaciones Biomédicas CEINBIO. School of Medicine, University of the Uruguayan Republic, UDELAR, Uruguay
This project is being developed on the perinatal unit of the University Hospital, at the neonatal pathology area working with a neonatal piglet model with high translational value, with partnership of CEINBIO.