Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study
| Autor: | Nicola Pelizzi, Alan Bainbridge, Ingran Lingam, Christopher Meehan, Adnan Avdic-Belltheus, Xavier Golay, Giancarlo Aquino, Sara Ragab, Benita Middleton, Kathryn A. Martinello, Daniel Alonso-Alconada, Mariya Hristova, Mohamed Tachrount, Fabrizio Facchinetti, Nicola J. Robertson, Annamaria Soliani Raschini, David Price, Magdalena Sokolska |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Neurobiology of Disease, Vol 121, Iss, Pp 240-251 (2019) |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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