Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study.

Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study. Neurobiol Dis. 2018 Oct 06;: Authors: Robertson NJ, Martinello K, Lingam I, Avdic-Belltheus A, Meehan C, Alonso-Alconada D, Ragab S, Bainbridge A, Sokolowska M, Tachrout M, Middleton B, Price D, Hristova M, Golay X, Raschini AS, Aquino G, Pelizzi N, Facchinetti F 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 and15 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 H...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research