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Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study
- Source :
- Neurobiology of Disease, Vol 121, Iss, Pp 240-251 (2019)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- Therapeutic hypothermia is only partially protective for neonatal encephalopathy; there is an urgent need to develop treatments that augment cooling. Our objective was to assess safety, efficacy and pharmacokinetics of 5 and 15 mg/kg/24 h melatonin (proprietary formulation) administered at 2 h and 26 h after hypoxia-ischemia (HI) with cooling in a piglet model. Following moderate cerebral HI, 30 piglets were eligible and randomized to: i) Hypothermia (33.5 °C, 2–26 h) and vehicle (HT + V;n = 13); b) HT and 5 mg/kg melatonin over 6 h at 2 h and 26 h after HI (HT + Mel-5;n = 4); c) HT and 15 mg/kg melatonin over 6 h at 2 h and 26 h after HI (HT + Mel-15;n = 13). Intensive care was maintained for 48 h; brain MRS was acquired and cell death (TUNEL) evaluated at 48 h. Comparing HT + V with HT + Mel-5 and HT + Mel-15, there was no difference in blood pressure or inotropic support needed, brain Lactate/N Acetylaspartate at 24 h and 48 h was similar, ATP/phosphate pool was higher for HT + Mel-15 versus HT + V at 24 h (p = 0.038) but not 48 h. A localized reduction in TUNEL positive cell death was observed in the sensorimotor cortex in the 15 mg/kg melatonin group (HT + Mel-15 versus HT + V; p
- Subjects :
- 0301 basic medicine
Inotrope
Sus scrofa
Pharmacology
lcsh:RC321-571
Translational Research, Biomedical
Melatonin
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Hypothermia, Induced
Intensive care
Animals
Medicine
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
TUNEL assay
business.industry
Neonatal encephalopathy
Brain
Hypothermia
medicine.disease
Disease Models, Animal
Neuroprotective Agents
030104 developmental biology
Blood pressure
Neurology
Hypoxia-Ischemia, Brain
medicine.symptom
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease, Vol 121, Iss, Pp 240-251 (2019)
- Accession number :
- edsair.doi.dedup.....e05dc5e00427520ca9fb18a76929f2c9