@article{MTMT:2828048,
	title = {Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model.},
	url = {https://m2.mtmt.hu/api/publication/2828048},
	author = {Robertson, NJ and Faulkner, S and Fleiss, B and Bainbridge, A and Andorka, Csilla and Price, D and Powell, E and Lecky-Thompson, L and Thei, L and Chandrasekaran, M and Hristova, M and Cady, EB and Gressens, P and Golay, X and Raivich, G},
	doi = {10.1093/brain/aws285},
	journal-iso = {BRAIN},
	journal = {BRAIN},
	volume = {136},
	unique-id = {2828048},
	issn = {0006-8950},
	abstract = {Despite treatment with therapeutic hypothermia, almost 50% of infants with neonatal encephalopathy still have adverse outcomes. Additional treatments are required to maximize neuroprotection. Melatonin is a naturally occurring hormone involved in physiological processes that also has neuroprotective actions against hypoxic-ischaemic brain injury in animal models. The objective of this study was to assess neuroprotective effects of combining melatonin with therapeutic hypothermia after transient hypoxia-ischaemia in a piglet model of perinatal asphyxia using clinically relevant magnetic resonance spectroscopy biomarkers supported by immunohistochemistry. After a quantified global hypoxic-ischaemic insult, 17 newborn piglets were randomized to the following: (i) therapeutic hypothermia (33.5 degrees C from 2 to 26 h after resuscitation, n = 8) and (ii) therapeutic hypothermia plus intravenous melatonin (5 mg/kg/h over 6 h started at 10 min after resuscitation and repeated at 24 h, n = 9). Cortical white matter and deep grey matter voxel proton and whole brain (31)P magnetic resonance spectroscopy were acquired before and during hypoxia-ischaemia, at 24 and 48 h after resuscitation. There was no difference in baseline variables, insult severity or any physiological or biochemical measure, including mean arterial blood pressure and inotrope use during the 48 h after hypoxia-ischaemia. Plasma levels of melatonin were 10 000 times higher in the hypothermia plus melatonin than hypothermia alone group. Melatonin-augmented hypothermia significantly reduced the hypoxic-ischaemic-induced increase in the area under the curve for proton magnetic resonance spectroscopy lactate/N-acetyl aspartate and lactate/total creatine ratios in the deep grey matter. Melatonin-augmented hypothermia increased levels of whole brain (31)P magnetic resonance spectroscopy nucleotide triphosphate/exchangeable phosphate pool. Correlating with improved cerebral energy metabolism, TUNEL-positive nuclei were reduced in the hypothermia plus melatonin group compared with hypothermia alone in the thalamus, internal capsule, putamen and caudate, and there was reduced cleaved caspase 3 in the thalamus. Although total numbers of microglia were not decreased in grey or white matter, expression of the prototypical cytotoxic microglial activation marker CD86 was decreased in the cortex at 48 h after hypoxia-ischaemia. The safety and improved neuroprotection with a combination of melatonin with cooling support phase II clinical trials in infants with moderate and severe neonatal encephalopathy.},
	keywords = {Animals; Male; Humans; SWINE; Treatment Outcome; Animals, Newborn; Disease Models, Animal; Infant, Newborn; resuscitation; Magnetic Resonance Spectroscopy; Brain/*drug effects/metabolism/pathology; Blood Pressure/drug effects/physiology; Hypothermia, Induced/*methods; Neuroprotective Agents/pharmacology/*therapeutic use; Energy Metabolism/drug effects/physiology; Melatonin/blood/pharmacology/*therapeutic use; Hypoxia-Ischemia, Brain/metabolism/pathology/*therapy; Asphyxia Neonatorum/metabolism/pathology/therapy},
	year = {2013},
	eissn = {1460-2156},
	pages = {90-105},
	orcid-numbers = {Andorka, Csilla/0000-0002-9714-1111}
}

@article{MTMT:1065485,
	title = {Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain},
	url = {https://m2.mtmt.hu/api/publication/1065485},
	author = {Kékesi, Adrienna Katalin and Kovács, Zsolt and Szilágyi, Nóra and Bobest, Mátyás and Szikra, Tamás and Dobolyi, Árpád and Juhász, Gábor Dénes and Palkovits, Miklós},
	doi = {10.1007/s10571-006-9103-3},
	journal-iso = {CELL MOL NEUROBIOL},
	journal = {CELLULAR AND MOLECULAR NEUROBIOLOGY},
	volume = {26},
	unique-id = {1065485},
	issn = {0272-4340},
	abstract = {1. Nucleosides potentially participate in the neuronal functions of the brain. However, their distribution and changes in their concentrations in the human brain is not known. For better understanding of nucleoside functions, changes of nucleoside concentrations by age and a complete map of nucleoside levels in the human brain are actual requirements.2. We used post mortem human brain samples in the experiments and applied a recently modified HPLC method for the measurement of nucleosides. To estimate concentrations and patterns of nucleosides in alive human brain we used a recently developed reverse extrapolation method and multivariate statistical analyses.3. We analyzed four nucleosides and three nucleobases in human cerebellar, cerebral cortices and in white matter in young and old adults. Average concentrations of the 308 samples investigated (mean+/-SEM) were the following (pmol/mg wet tissue weight): adenosine 10.3+/-0.6, inosine 69.5+/-1.7, guanosine 13.5+/-0.4, uridine 52.4+/-1.2, uracil 8.4+/-0.3, hypoxanthine 108.6+/-2.0 and xanthine 54.8+/-1.3. We also demonstrated that concentrations of inosine and adenosine in the cerebral cortex and guanosine in the cerebral white matter are age-dependent.4. Using multivariate statistical analyses and degradation coefficients, we present an uneven regional distribution of nucleosides in the human brain. The methods presented here allow to creation of a nucleoside map of the human brain by measuring the concentration of nucleosides in microdissected tissue samples. Our data support a functional role for nucleosides in the brain.},
	year = {2006},
	eissn = {1573-6830},
	pages = {833-844},
	orcid-numbers = {Kékesi, Adrienna Katalin/0000-0003-3042-4878; Kovács, Zsolt/0000-0001-8571-5686; Dobolyi, Árpád/0000-0003-0397-2991; Juhász, Gábor Dénes/0000-0002-0849-6931; Palkovits, Miklós/0000-0003-0578-0387}
}