Table 1.
Summary of study characteristics.
| Publication | Species, age, sex | HT | Anaesthesia | Brain injury | Dosing regime | Melatonin Dose mg/kg (HED) | Excipient | Melatonin levels (Cmax) mg/L | Duration of experiment (days) | Infarct size | Neurobehavioural tests | Histological assessment of cell death |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Carloni (2008) | Rat, P7, NS | No | Isoflurane | Carotid artery ligation, ↓FiO2 | Intraperitoneal: Pre‐HI, 5 min after HI, 24 h, 48 h | 15 (2.6) | 5% DMSO | Not reported | 60 | % ipsilateral injury using toluidine blue staining | Circular maze test | No response to data request |
| Cetinkaya (2011) | Rat, P7, mixed | No | Isoflurane | Carotid artery ligation ↓FiO2 | Intraperitoneal: Pre‐HI, immediate after HI, 24 h | 40 (7) | 10% ethanol | Not reported | 3 | % infarct volume with TTC | NS | No response to data request |
| Alonso‐Alconada (2012) | Rat, P7, NS | No | Isoflurane | Carotid artery ligation ↓FiO2 | Intraperitoneal: 5 mins after HI, 24 h, 48 h | 15 (2.6) | 5% DMSO | Not reported | 7 | Mean left:right hemisphere area ratio using cresyl violet staining | NS | qualitative only |
| Ozyener (2012) | Rat, P7, mixed | No | Isoflurane | Carotid artery ligation ↓FiO2 | Intraperitoneal: Pre HI, immediate after HI, 24 h | 40 (7) | 10% ethanol | Not reported | 3 | % infarct volume with TTC | NS | No response to data request |
| Yawno (2012) | Lamb, 126 days, mixed | No | Halothane | Umbilical cord occlusion | intravenous: 2 h before HI | 0.75 (0.82) | 1% ethanol | Not reported | 2 | NS | NS | CC3 |
| Robertson (2013) | Piglet, <48 h old, Male | Yes | Isoflurane | Carotid artery ligation ↓FiO2 | Intravenous Infusion over 6 h: Immediately after HI, 24 h | 30 (26.2) | 2.5% ethanol | 21 | 2 | NS | NS | TUNEL |
| Revuelta (2017) | Rat, P7, NS | No | Isoflurane | Carotid artery ligation ↓FiO2 | Intraperitoneal: after HI | 15 (2.6) | 5% DMSO | Not reported | 7 | NS | NS | NeuN |
| Aridas (2018) | Lamb, 139–141 l days, mixed | No | Sodium thiopentone | Umbilical cord occlusion | Intravenous boluses of 5 mg every 2 h, from 30 min to 24.5 h after HI | 15 (16.5) | 3% ethanol | <1 | 3 | NS | Feeding, suckle, tone, standing | CC3 |
| Berger (2019) | Rat, P7, mixed | No | Isoflurane | Carotid artery ligation ↓FiO2 | Intraperitoneal: After HI, 6 h, 25 h | 20 (3.5) | 5% DMSO | Not reported | 43 | NS | Cylinder test, novel object recognition | H&E |
| Robertson (2019) | Piglet, <48 h old, male | Yes | Isoflurane | Carotid artery ligation ↓FiO2 | Intravenous 2 h infusion: 1 h after HI, 26 h | 15 (13.1) | Ehanol‐free | 16.8 | 2 | NS | NS | TUNEL |
| Robertson (2020) | Piglet, <48 h old, male | Yes | Isoflurane | Carotid artery ligation ↓FiO2 | Intravenous 6 h infusion: 1 h after HI, 24 h | 18 (15.7) | 2.5% ethanol | 18.8 | 2 | NS | NS | TUNEL |
| Aridas (2021) | Lamb, 139–141 days, mixed | Both | Sodium Thiopentone | Umbilical cord occlusion | Intravenous boluses of 5 mg every 2 h, 30 min to 24.5 h after HI | 15 (16.5) | 5% ethanol | <1 | 3 | NS | Standing, feeding | CC3 |
| Pang (2021) | Piglet, <48 h old, male | Yes | Isoflurane | Carotid artery ligation ↓FiO2 | Intravenous 2 h infusion: 1 h after HI, 24 h, 48 h | 20 (17.5) | Ehanol‐free | 27.8 | 3 | NS | NS | TUNEL |
| Sun (2021) | Mouse, P10, mixed | No | Diethyl ether | Carotid artery ligation ↓FiO2 | Intravenous boluses of 5 mg every 2 h, 30 min to 24.5 h after HI: Immediately after HI, repeated every 24 h for 28 days | 10 (1.2) | 3% tween | NS | 28 | % infarct volume with TTC | Negative geotaxis, cliff avoidance, Forelimb suspension, surface righting, novel object recognition, open field, step‐through, foot fault, cylinder tests | NS |
CC3, cleaved‐caspase‐3; DMSO, diethyl sulfoxide; H&E, haematoxylin and eosin; HT, hypothermia; HED, human equivalent dose; NeuN, neuronal nuclei; TTC, triphenyltetrazolium chloride; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labelling; NS, not stated.