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Na+/H+ exchanger ( NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy ( MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride ( MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (31P) and proton (1H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve ( AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling ( TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model. [ABSTRACT FROM AUTHOR]

Abstract: Background: Early childhood is an important period for the development of sleep patterns; studies of sleep patterns in young preschool children may help elucidate the mechanism of associated mental/physical conditions and later sleep problems. Aim and methods: The aim of this study was to investigate intrinsic and extrinsic independent variables associated with sleep patterns in preschool children using actigraphy. Forty-eight 5-year-old children from two types of nurseries, which accommodate children with (Type A) or without (Type B) in-home caregivers, were invited to undergo a 7-day actigraphic sleep study. Results: Compared with weekdays, both sleep onset time and sleep end time were later on weekends (28 and 17min later in average, respectively). On weekdays, cultural lessons were associated with a later sleep onset time (22min later); female gender, sports lessons and fixed bathing times were related with an earlier sleep end time (17, 21 and 17min earlier, respectively); sports lessons were also associated with higher sleep efficiency (3.7% higher). During weekends, unfixed bedtimes and daytime naps were related with a later sleep onset time (73 and 54min later, respectively); male gender, Type A nursery and daytime naps were associated with a later sleep end time (33, 37 and 34min later, respectively); sports lessons were associated with higher sleep efficiency (3.6% higher). Conclusions: Our current findings suggested that both intrinsic and extrinsic factors, such as gender, child care, lifestyle and after-nursery lessons, influence the establishment of sleep patterns in young preschool children. Further investigation of these independent variables may help establish a strategy for predicting and preventing sleep disorders later in life. [Copyright &y& Elsevier]

Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012-2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies. [ABSTRACT FROM AUTHOR]

Neuroprotection following brain injury has been a top priority in neuroscience since the Hippocratic era. However, of hundreds of "experimentally-neuroprotective treatments", currently only hypothermia is clinically available. Interpretation of bench-work may have to account for the variation in developmental stages and types of injury. For example GABAergic stimulators have been used to reduce cerebral energy consumption; recent studies suggested the paradoxical excitation of premature neurons following GABAergic stimuli because of the high intracellular chloride concentration during the perinatal period. Even for hypothermia, many questions remain unanswered:selective-head cooling following perinatal hypoxia-ischemia appeared rather deleterious for infants with the most severe encephalopathy or low birth-weight. In a piglet model, different cooling levels provided differential regional brain protection:35 degrees C was optimal for deep-grey-matter whereas the cortical-grey-matter was better protected at 33 degrees C, suggesting that a single cooling level may not be equally optimal for the entire brain. Another experimental study used magnetic-resonance spectroscopy to demonstrate that the more severe the acute event was, the shorter the therapeutic time window was, explaining the lower effectiveness of neuroprotection following the most severe hypoxia-ischemia. Another suggestion from our translational research was the dependence of cerebral temperatures on body weight under selective-head cooling:the smaller the body weight, the lower the brain temperature, presumably because of the larger surface area to brain volume ratio in small subjects. Thus translational research is essential to achieve "tailored" treatments, that address for individual and regional cerebral conditions. Although therapeutic options have become available in the tertiary centre settings, neuroprotection should not remain an expensive treatment only available in rich countries. We have recently developed a cooling system that can maintain stable hypothermia over 24 hours without an electric supply. Experimental studies to optimise high-tech cooling need to run in parallel with studies to increase the distribution of these treatments worldwide.

Objectives: Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the "latent phase" may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33 degrees C or 35 degrees C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI., Methods: Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35 degrees C (HI-35; n = 7), and (3) HI-Trectal 33 degrees C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed., Results: Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming., Conclusions: Whole-body hypothermia for 24 hours at either 35 or 33 degrees C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33 degrees C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.