期刊
PEDIATRIC RESEARCH
卷 80, 期 5, 页码 710-718出版社
SPRINGERNATURE
DOI: 10.1038/pr.2016.149
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资金
- Lebara Foundation (London EC2R 7BP, UK)
- Laerdal Foundation (Stavanger, Norway)
- Renee og Bredo Grimsgaard's Foundation (Oslo, Norway)
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% O-2 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 1 mg/kg, VEH+hypothermia (H) or CBD 1 mg/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 gelatinise-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.
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