TY - JOUR AU - Robertson, NJ AU - Faulkner, S AU - Fleiss, B AU - Bainbridge, A AU - Andorka, Csilla AU - Price, D AU - Powell, E AU - Lecky-Thompson, L AU - Thei, L AU - Chandrasekaran, M AU - Hristova, M AU - Cady, EB AU - Gressens, P AU - Golay, X AU - Raivich, G TI - Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model. JF - BRAIN J2 - BRAIN VL - 136 PY - 2013 IS - Pt 1 SP - 90 EP - 105 PG - 16 SN - 0006-8950 DO - 10.1093/brain/aws285 UR - https://m2.mtmt.hu/api/publication/2828048 ID - 2828048 N1 - Megjegyzés-24407903 PN 1 Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, United Kingdom Department of Surgery and Cancer, Centre for the Developing Brain, Institute of Reproductive and Developmental Biology, London W12 ONN, United Kingdom Inserm U676, Hôpital Robert-Debré, 75019 Paris, France Faculté de Médecine, Université Paris Diderot, 75205 Paris, France Department of Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London WC1E 6DB, United Kingdom UCL Institute of Neurology, London WC1N 3BG, United Kingdom Cited By :143 Export Date: 20 February 2020 CODEN: BRAIA Correspondence Address: Robertson, N.J.; Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, United Kingdom; email: n.robertson@ucl.ac.uk Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, United Kingdom Department of Surgery and Cancer, Centre for the Developing Brain, Institute of Reproductive and Developmental Biology, London W12 ONN, United Kingdom Inserm U676, Hôpital Robert-Debré, 75019 Paris, France Faculté de Médecine, Université Paris Diderot, 75205 Paris, France Department of Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London WC1E 6DB, United Kingdom UCL Institute of Neurology, London WC1N 3BG, United Kingdom Cited By :153 Export Date: 17 August 2020 CODEN: BRAIA Correspondence Address: Robertson, N.J.; Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, United Kingdom; email: n.robertson@ucl.ac.uk AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kékesi, Adrienna Katalin AU - Kovács, Zsolt AU - Szilágyi, Nóra AU - Bobest, Mátyás AU - Szikra, Tamás AU - Dobolyi, Árpád AU - Juhász, Gábor Dénes AU - Palkovits, Miklós TI - Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain JF - CELLULAR AND MOLECULAR NEUROBIOLOGY J2 - CELL MOL NEUROBIOL VL - 26 PY - 2006 IS - 4-6 SP - 833 EP - 844 PG - 12 SN - 0272-4340 DO - 10.1007/s10571-006-9103-3 UR - https://m2.mtmt.hu/api/publication/1065485 ID - 1065485 N1 - Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary Department of Zoology, Berzsenyi Dániel College, Szombathely, Hungary Research Group of Neurobiology, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary Markusovszky Hospital, Szombathely, Hungary Laboratory of Neuromorphology, Hungarian Academy of Sciences, Semmelweis University, Tüzoltó-utca 58, Budapest 1094, Hungary Cited By :14 Export Date: 25 October 2022 CODEN: CMNED Correspondence Address: Palkovits, M.; Laboratory of Neuromorphology, Tüzoltó-utca 58, Budapest 1094, Hungary; email: palkovits@ana.sote.hu AB - 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. LA - English DB - MTMT ER -