title: Short-term effects of cannabidiol after global hypoxia-ischemia in newborn piglets.
abstract: Cannabidiol (CBD), a nonpsychoactive cannabinoid, has shown neuroprotective actions after neonatal hypoxia-ischemia (HI) in animals. We wanted to further explore the effects of CBD, alone and in conjunction with hypothermia, in a piglet model of global HI.
  
  
  
  Fifty-five anesthetized newborn piglets were randomized to either controls (n = 7) or HI (n = 48) by ventilation with 8% O2until mean arterial blood pressure reached 20 mmHg and/or base excess reached -20 mmol/l. After resuscitation piglets were randomized to either: vehicle (VEH), CBD 1mg/kg, VEH+hypothermia (H) or CBD 1mg/kg+H (each n = 12). Piglets were euthanized 9.5 h after HI and plasma, urine, cerebrospinal fluid, and brain tissue were sampled for analysis.
  
  
  
  HI induced global damage with significantly increased neuropathology score, S100B in cerebrospinal fluid, hippocampal proton magnetic resonance spectroscopy biomarkers, plasma troponin-T, and urinary neutrophil gelatinase-associated lipocalin. CBD alone did not have any significant effects on these parameters while CBD+H reduced urinary neutrophil gelatinase-associated lipocalin compared with VEH+H (P < 0.05). Both hypothermic groups had significantly lower glutamate/N-acetylaspartate ratios (P < 0.01) and plasma troponin-T (P<0.05) levels compared with normothermic groups.
  
  
  
  In contrast to previous studies, we do not find significant protective effects of CBD after HI in piglets. Evaluation of CBD in higher doses might be warranted.
authors.affiliation: Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Håvard T
authors.initials: HT
authors.lastname: Garberg
authors.affiliation: Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Marianne U
authors.initials: MU
authors.lastname: Huun
authors.affiliation: Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Neonatal Research Unit, Health Research Institute Hospital La Fe, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escobar
authors.affiliation: Division of Neonatology. Hospital Clinico San carlos-IdISSC, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez-Orgado
authors.affiliation: Department of Pathology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Else-Marit
authors.initials: EM
authors.lastname: Løberg
authors.affiliation: Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Rønnaug
authors.initials: R
authors.lastname: Solberg
authors.affiliation: Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Ola
authors.initials: O
authors.lastname: Didrik Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002185:Cannabidiol / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010100:Oxygen; D013552:Swine
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D002185:Cannabidiol; D010100:Oxygen