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Pediatr Res. 2016 Nov;80(5):710-718. doi: 10.1038/pr.2016.149. Epub 2016 Jul 21.

Short-term effects of cannabidiol after global hypoxia-ischemia in newborn piglets.

Author information

1
Department of Pediatric Research, Women and Children's Division and Institute for Surgical research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
2
University of Oslo, Oslo, Norway.
3
Neonatal Research Unit, Health Research Institute Hospital La Fe, Valencia, Spain.
4
Division of Neonatology. Hospital Clinico San carlos-IdISSC, Madrid, Spain.
5
Department of Pathology, Oslo University Hospital, Ullevål, Oslo, Norway.

Abstract

BACKGROUND:

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.

METHODS:

Fifty-five anesthetized newborn piglets were randomized to either controls (n = 7) or HI (n = 48) by ventilation with 8% O2 until 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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
27441365
DOI:
10.1038/pr.2016.149
[Indexed for MEDLINE]

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