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PO-0483d No Neuroprotective Effects Of Cannabidiol After Severe Hypoxia-ischemia In Newborn Piglets
  1. HT Garberg1,
  2. MU Huun1,
  3. J Escobar2,
  4. J Martinez Orgado3,
  5. R Solberg1,
  6. OD Saugstad1
  1. 1Department of Pediatric Research, Oslo University Hospital, Oslo, Norway
  2. 2Research Unit, Health Research Institute Hospital La Fé, Valencia, Spain
  3. 3Experimental Unit, Pediatric Department University Hospital Puerta de Hierro Majadahonda, Madrid, Spain

Abstract

Background and aim Hypothermia is limiting neurological sequela after perinatal asphyxia. Still a significant number of infants have minimal effect of the treatment. Adjuvant neuroprotective strategies are therefore needed. In animal studies the phytocannabinoid Cannabidiol (CBD) has shown great promise as a neuroprotective agent. The aim of this study was to explore the neuroprotective properties of CBD after hypoxia ischemia in newborn piglets.

Materials and method 54 anaesthetised piglets (age 12–36 h) were randomised to either undergo global hypoxia (n = 48) until the base excess reached -20 mmol/L or the mean arterial blood pressure dropped below 20 mm Hg or to the SHAM group (n = 6). After hypoxia piglets were randomised to the different study groups : Hypoxia+CBD (1 mg/kg) (n = 12), Hypoxia+CBD(1 mg/kg)+hypothermia (n = 12), hypoxia (n = 12) or hypoxia+hypothermia (n = 12). 9,5 h after end of hypoxia the piglets were euthanized and samples from hippocampus were snap frozen in liquid nitrogen. Levels of lactate (lac), n-acetylaspartate (NAA) and glutamate (glu) were measured by proton-magnetic-resonance-spectroscopy (H±-MRS)- and ratios predictive of neurodevelopmental outcome after hypoxic-ischaemic encephalopathy in newborns where calculated (lac/NAA and glu/NAA). Outliers > 2,5 SD away from mean were removed before analysis.

Discussion Hypoxia significantly increased both Lac/NAA and Glu/NAA ratios. Hypothermia groups were comparable to SHAM while there were no significant effects of CBD on these MRS biomarkers. The difference in the way of inducing and the severity of hypoxia-ischemia in our model might explain this lack of effect compared to previously published studies.

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