The effects of anaesthesia on cell death in a porcine model of neonatal hypoxic-ischaemic brain injury

Background: Hypothermia is neuroprotective after neonatal hypoxic-ischaemic brain injury. However, systemic cooling to hypothermic temperatures is a stressor and may reduce neuroprotection in awake pigs. We compared two experiments of global hypoxic-ischaemic injury in newborn pigs, in which one group received propofol–remifentanil and the other remained awake during post-insult hypothermia treatment. Methods: In both studies, newborn pigs were anaesthetised using halothane during a 45-min global hypoxic-ischaemic insult induced by reducing Fio2 and graded hypotension until a low-voltage <7 μV electroencephalogram was achieved. On reoxygenation, the pigs were randomly allocated to receive 24 h of normothermia or hypothermia. In the first study (n=18) anaesthesia was discontinued and the pigs' tracheas were extubated. In the second study (n=14) anaesthesia was continued using propofol and remifentanil. Brain injury was assessed after 72 h by classical global histopathology, Purkinje cell count, and apoptotic cell counts in the hippocampus and cerebellum. Results: Global injury was nearly 10-fold greater in the awake group compared with the anaesthetised group (P=0.021). Hypothermia was neuroprotective in the anaesthetised pigs but not the awake pigs. In the hippocampus, the density of cleaved caspase-3-positive cells was increased in awake compared with anaesthetised pigs in normothermia. In the cerebellum, Purkinje cell density was reduced in the awake pigs irrespective of treatment, and the number of cleaved caspase-3-positive Purkinje cells was greatly increased in hypothermic awake pigs. We detected no difference in cleaved caspase-3 in the granular cell layer or microglial reactivity across the groups. Conclusions: Our study provides novel insights into the significance of anaesthesia/sedation during hypothermia for achieving optimal neuroprotection

Two modes of glacial climate during the late stage 5 identified in Greenland ice core records

International audienceFrom a detailed analysis of marine and terrestrial aerosol tracers in the NGRIP ice core we identified two distinct glacial atmospheric flow patterns. The climate transition from Marine Isotope Stage 5 (MIS 5) to MIS 4, at approximately 75 kyr BP, marks a shift between two different atmospheric flow regimes. Before this transition, during MIS 5d-a, the state of atmospheric flow was alternating between the two modes of different flow patterns, while a more persistent flow pattern was prevailing through the glacial period afterwards. These changes are accompanied by strong changes in an independent Greenland ice core proxy, namely the deuterium excess from the GRIP ice core, reflecting changes in the hydrological cycle and moisture source temperatures as well. The changes in atmospheric flow pattern are correlated with changed extent of ice-rafted detritus (IRD) deposition in the North Atlantic, indicating that the state of the atmospheric flow was highly sensitive to the waxing and waning of the Laurentide ice sheet

Morphine and fentanyl exposure during therapeutic hypothermia does not impair neurodevelopment

Background Hypothermia-treated and intubated infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) usually receive morphine for sedation and analgesia (SA) during therapeutic hypothermia (TH) and endotracheal ventilation. Altered drug pharmacokinetics in this population increases the risk of drug accumulation. Opioids are neurotoxic in preterm infants. In term infants undergoing TH, the long-term effects of morphine exposure are unknown. We examined the effect of opioid administration during TH on neurodevelopmental outcome and time to extubation after sedation ended. Methods In this prospectively collected population-based cohort of 282 infants with HIE treated with TH (2007–2017), the cumulative opioid dose of morphine and equipotent fentanyl (10–60 µg/kg/h) administered during the first week of life was calculated. Clinical outcomes and concomitant medications were also collected. Of 258 survivors, 229 underwent Bayley-3 neurodevelopmental assessments of cognition, language and motor function at 18–24 months. Multivariate stepwise linear regression analysis was used to examine the relation between cumulative opioid dose and Bayley-3 scores. Three severity-groups (mild-moderate-severe) were stratified by early (<6 h) amplitude-integrated electroencephalography (aEEG) patterns. Findings The cumulative dose of opioid administered as SA during TH was median (IQR) 2121 µg/kg (1343, 2741). Time to extubation was independent of SA dose (p > 0.2). There was no significant association between cumulative SA dose and any of the Bayley-3 domains when analysing the entire cohort or any of the aEEG severity groups. Interpretation Higher cumulative opioid doses in TH-treated infants with HIE was not associated with worse Bayley-3 scores at 18–24 months of age. Funding The Bristol cooling program was funded by the Children's Medical Research Charity SPARKS managing donations for our research from the UK and US, the UK Moulton Foundation, the Lærdal Foundation for Acute Medicine in Norway and the Norwegian Research Council (JKG)

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

On the Transmission of Information through Sensory Neurons

Information about muscle length is transmitted to the cerebellum from muscle spindle receptors through the dorsal spinocerebellar tract (DSCT). The “transinformation” about muscle length in single DSCT fibers was calculated from steady-state spike trains by two different methods, assuming that the decoding mechanisms use a frequency code. By the first method, the number of distinguishable muscle lengths (and thus the transiformation) was determined from the rate of convergence of the mean frequency of firing (with increasing number of intervals). The observation time necessary to estimate the mean frequency of the impulse train with a certain accuracy was independent of the stretch level, even though the number of intervals necessary to make this estimate was different at high and low levels of stretch. By the second method an input frequency-output frequency matrix was calculated. The transinformations and the rate of transinformation was then calculated from this matrix. There was an acceptable agreement in the estimates of transinformation by the two methods. The rates of transinformation are significantly increased by the particular time structure of the discharge patterns of the nerve cells. Consequently, the loss of information due to the synaptic coupling is appreciably reduced