Browsing by Subject "birth asphyxia"

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  • Alafuzoff, Aleksander (Helsingfors universitet, 2016)
    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.
  • Summanen, Milla; Back, Susanne; Voipio, Juha; Kaila, Kai (2018)
    Mammalian birth is accompanied by a period of obligatory asphyxia, which consists of hypoxia (drop in blood O-2 levels) and hypercapnia (elevation of blood CO2 levels). Prolonged, complicated birth can extend the asphyxic period, leading to a pathophysiological situation, and in humans, to the diagnosis of clinical birth asphyxia, the main cause of hypoxic-ischemic encephalopathy (HIE). The neuroendocrine component of birth asphyxia, in particular the increase in circulating levels of arginine vasopressin (AVP), has been extensively studied in humans. Here we show for the first time that normal rat birth is also accompanied by an AVP surge, and that the fetal AVP surge is further enhanced in a model of birth asphyxia, based on exposing 6-day old rat pups to a gas mixture containing 4% O-2 and 20% CO2 for 45 min. Instead of AVP, which is highly unstable with a short plasma half-life, we measured the levels of copeptin, the C-terminal part of prepro-AVP that is biochemically much more stable. In our animal model, the bulk of AVP/copeptin release occurred at the beginning of asphyxia (mean 7.8 nM after 15 min of asphyxia), but some release was still ongoing even 90 min after the end of the 45 min experimental asphyxia (mean 1.2 nM). Notably, the highest copeptin levels were measured after hypoxia alone (mean 14.1 nM at 45 min), whereas copeptin levels were low during hypercapnia alone (mean 2.7 nM at 45 min), indicating that the hypoxia component of asphyxia is responsible for the increase in AVP/copeptin release. Alternating the O-2 level between 5 and 9% (CO2 at 20%) with 5 min intervals to mimic intermittent asphyxia during prolonged labor resulted in a slower but quantitatively similar rise in copeptin (peak of 8.3 nM at 30 min). Finally, we demonstrate that our rat model satisfies the standard acid-base criteria for birth asphyxia diagnosis, namely a drop in blood pH below 7.0 and the formation of a negative base excess exceeding -11.2 mmol/l. The mechanistic insights from our work validate the use of the present rodent model in preclinical work on birth asphyxia.
  • Spoljaric, Albert; Seja, Patricia; Spoljaric, Inkeri; Virtanen, Mari A.; Lindfors, Jenna; Uvarov, Pavel; Summanen, Milla; Crow, Ailey K.; Hsueh, Brian; Puskarjov, Martin; Ruusuvuori, Eva; Voipio, Juha; Deisseroth, Karl; Kaila, Kai (2017)
    During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABA(A) receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.