Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome

The objective of this study was to evaluate the early changes in serial serum levels of copeptin and neuron-specific enolase (NSE) in neonates diagnosed with birth asphyxia, and to determine whether these biomarkers measured in the first 168 hours after birth are predictive of long-term neurodevelopmental outcome. Copeptin and NSE levels were measured from serum samples collected 6, 12, 24, 48, 72, and 168 hours after birth from 75 term neonates diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia for 72 hours. In addition, serum copeptin levels after birth were measured from 10 HIE diagnosed neonates, who were randomized to the normothermic arm of the TOBY cohort. All neonates underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development-II at two years of age. Copeptin levels were highest at 6 hours after birth and steadily decreased, whereas the highest NSE levels were measured at 24 hours after birth. The biomarker levels correlated with blood-gas parameters (base excess, pH and lactate) at 6 and 12 hours after birth. Copeptin and NSE levels in the early postnatal period were significantly higher in neonates with poor outcome compared to those with favorable outcome at two years of age. Furthermore, in the TOBY cohort, copeptin levels were significantly lower in hypothermic compared to normothermic neonates. To conclude, copeptin and NSE measured in the early postnatal period are potential prognostic biomarkers of long-term neurodevelopmental outcome in term neonates diagnosed with HIE and treated with therapeutic hypothermia.Peer reviewe

Using Galvanic Vestibular Stimulation to Sense Abstract Data

We propose using galvanic vestibular stimulation for presenting abstract data, for instance stock market trends. Using galvanic vestibular stimulation, data is felt directly as a perturbation in the sense of balance. This work is showcased as an art performance, where stock market fluctuations cause a person to maintain or lose balance. We present the artistic and technical principles underlying the performance and describe the technical implementation of a working system. The work shows how abstract data can be presented in a way that is not limited to visual, auditory, olfactory, or tactile sensing.Peer reviewe

Muuttuneet hippokampaaliset terävät aallot syntymän aikaisen asfyksian rottamallissa

Background. Birth asphyxia is a pathological state that occurs if fetal gas exchange is disrupted for an extended period of time during delivery. Prolonged birth asphyxia causes brain damage and can even lead to death, but which in mild and moderate cases causes motor and cognitive disability. One of the brain regions often damaged is the hippocampus, which is known to play a major role in memory processing. Thus, damage to the hippocampus may in part explain the long-term cognitive consequences of birth asphyxia. In the neonatal brain hippocampal network activity is discontinuous, dominated by sharp waves and oscillatory bouts, of which the former are thought to be important for memory consolidation in the adult brain. Later in development sharp waves exhibit fast oscillations called ripples that organise hippocampal activity after learning. The aim of this thesis was to establish how sharp wave signalling in the neonatal hippocampus is affected by birth asphyxia. Methods. A rat model developed at the Laboratory of Neurobiology, University of Helsinki, was used to study birth asphyxia and a putative therapeutic strategy. Neonatal rat pups aged 5-8 days were used in the study. These animals were randomly assigned to one of four experimental groups: naive control, sham control, asphyxia, and graded restoration of normocapnia. Hippocampal network activity was measured in vivo under urethane anaesthesia using local field potential (LFP) recordings 24 hours after the asphyxic insult. Sharp waves were detected and analysed in terms of event counts, timing, size, shape and ripple properties. Results and conclusions. After asphyxia, sharp waves occurred more frequently within clusters than in isolation. In addition, sharp wave ripples were detected for the first time during early neonatal development. In asphyxiated animals, the number and magnitude of detected ripples was statistically significantly decreased. Interestingly, animals that underwent graded restoration of normocapnia after asphyxia were no different from controls, suggesting a protective effect of the treatment. The abnormal SPW development after birth asphyxia may form a mechanism contributing to the emergence of cognitive deficits.Tausta. Syntymän aikainen asfyksia on patologinen tila, joka aiheutuu sikiön hapensaannin pitkäkestoisesta häiriöstä synnytyksen aikana. Pitkäkestoinen asfyksia vaurioittaa hermostoa ja voi johtaa äärimmillään kuolemaan, mutta lievemmissä tapauksissa se aiheuttaa kognitiivisia ja motorisia vammoja. Yksi aivoalue, jonka tiedetään vaurioituvan usein asfyksiassa, on hippokampus. Hippokampuksella tiedetään olevan tärkeä rooli pitkäkestoisten muistojen synnyssä, joten sen vauriot saattavat selittää asfyksian kognitiivisia seurauksia. Varhaiskehityksen aikana hippokampuksen verkkoaktiivisuus on jaksottaista ja sitä hallitsevat niin kutsutut terävät aallot ja lyhyet oskillaatiojaksot, joista ensimmäisten uskotaan olevan keskeisessä roolissa muistijälkien muodostuksessa aikuisiällä. Kehityksen myötä terävien aaltojen aikana havaitaan myös niin kutsuttuja teräväaalto-väreitä, joiden on osoitettu ohjaavan hippokampuksen toimintaa oppimisen jälkeen. Tämän tutkielman tarkoituksena oli selvittää, kuinka syntymänaikainen asfyksia muuttaa hippokampuksen teräviä aaltoja. Menetelmät. Syntymän aikaista asfyksiaa sekä mahdollista terapiamuotoa tutkittiin Helsingin yliopiston neurobiologian laboratoriossa kehitetyn rottamallin avulla. Tutkimuksessa käytettiin 5-8 päivän ikäisiä rotanpoikasia, jotka jaettiin neljään koeryhmään: naiivikontrolli, verrokkikontrolli, asfyksia sekä normokapnian porrastettu palautus. Hippokampuksen verkkoaktiivisuutta mitattiin in vivo uretaanianestesiassa paikallisten kenttäpotentiaalien (LFP) avulla 24 tuntia asfyksiakäsittelyn jälkeen. LFP-signaalista eroteltiin terävät aallot, joiden lukumäärää, ajoitusta, kokoa, muotoa, sekä teräväaalto-väreiden ominaisuuksia tarkasteltiin tutkimuksessa. Tulokset ja johtopäätökset. Asfyksian jälkeen terävät aallot esiintyivät useammin ryppäissä kuin erillään. Lisäksi tutkimuksessa havaittiin ensi kertaa teräväaalto-väreitä varhaiskehityksen aikana. Asfyksiaeläimillä väreiden lukumäärä sekä niiden koko oli tilastollisesti merkitsevästi vähentynyt. Mielenkiintoinen tulos oli myös se, että eläimet, joilla normokapnia palautettiin asfyksian jälkeen porrastetusti, eivät eronneet kontrolleista, mikä puoltaa käsittelyn hermostoa suojaavaan vaikutukseen. Asfyksian jälkeiset muutokset teräväaaltojen kehittymisessä voivat osallistua asfyksian pitkäkestoisten kognitiivisten häiriöiden syntyyn

A physiologically validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia

Objective Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term-equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia. Methods Postnatal day 11-12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O-2 + 20% CO2) or to intermittent asphyxia (30 min; three 5 + 5-min cycles of 9% and 5% O-2 at 20% CO2). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po-2, and local field potentials (LFPs) were made under urethane anesthesia. Results Both protocols decreased blood pH to Significance The rate of brain pH recovery has a strong influence on post-asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.Peer reviewe

Data from: Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome

The objective of this study was to evaluate the early changes in serial serum levels of copeptin and neuron-specific enolase (NSE) in neonates diagnosed with birth asphyxia, and to determine whether these biomarkers measured in the first 168 hours after birth are predictive of long-term neurodevelopmental outcome. Copeptin and NSE levels were measured from serum samples collected 6, 12, 24, 48, 72, and 168 hours after birth from 75 term neonates diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia for 72 hours. In addition, serum copeptin levels after birth were measured from 10 HIE diagnosed neonates, who were randomized to the normothermic arm of the TOBY cohort. All neonates underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development-II at two years of age. Copeptin levels were highest at 6 hours after birth and steadily decreased, whereas the highest NSE levels were measured at 24 hours after birth. The biomarker levels correlated with blood-gas parameters (base excess, pH and lactate) at 6 and 12 hours after birth. Copeptin and NSE levels in the early postnatal period were significantly higher in neonates with poor outcome compared to those with favorable outcome at two years of age. Furthermore, in the TOBY cohort, copeptin levels were significantly lower in hypothermic compared to normothermic neonates. To conclude, copeptin and NSE measured in the early postnatal period are potential prognostic biomarkers of long-term neurodevelopmental outcome in term neonates diagnosed with HIE and treated with therapeutic hypothermia

Minimal data set

Minimal data set for 2017 PLOS ONE article "Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome"

Clinical characteristics of the study groups.

<p>Clinical characteristics of the study groups.</p

Copeptin and NSE levels after birth in relation to two-year outcome.

<p>(A) Copeptin levels were significantly higher in neonates in the poor outcome group (n = 25) than in the favorable outcome group (n = 50) at 6 hours (p = 0.0068), 12 hours (p = 0.0050) and 48 hours (p = 0.0226) after birth. (B) NSE levels were significantly higher in the neonates in the poor outcome group compared to the favorable outcome group at all time points (p = 0.0009 at 6 hours, p = 0.0005 at 12 hours, p = 0.0005 at 24 hours, p = 0.0009 at 48 hours, and p = 0.0029 at 72 hours). (C-D) ROC curves of combined copeptin and NSE concentrations at 6 hours (C) and 12 hours (D) after birth in relation to two year neurodevelopmental outcome. Graphs A and B show the median ± IQR. The data for each time point were analyzed separately with the Mann-Whitney U-test, and the Holm-Sidak method was used to compute thresholds to ensure a family-wise error rate below 0.05.</p

Copeptin levels in relation to therapeutic hypothermia.

<p>Copeptin concentrations after birth were lower in the hypothermic neonates from the TOBY cohort (n = 11) compared to the normothermic neonates from the same cohort (n = 10) at 6 hours after birth (p = 0.0495). Graph shows the median ± IQR. The data for each time point was analyzed separately with the Mann-Whitney U-test, and the Holm-Sidak method was used to compute thresholds to ensure a family-wise error rate below 0.05.</p

Copeptin and NSE concentrations in serum samples over time (n = 75).

<p>(A, B) Copeptin levels decrease over time, with highest levels measured at 6 hours after birth. Copeptin concentrations are shown for individual neonates (A) as well as the median ±IQR concentration for each time point (B). Compared to the 6 hour time point, concentrations were significantly lower at all subsequent time points (p = 0.0448 at 6 vs. 12 hours, and p < 0.0001 at all other time points). (C, D) NSE levels are relatively stable until 24 h after birth, after which the levels decrease. Data is shown for individual neonates (C) and as the median ± IQR at each time point (D). Compared to the 6 hour time point, concentrations were significantly lower only at 168 hours after birth (p = 0.0013). The Kruskal-Wallis test with Dunn’s multiple comparisons test was used.</p