Oxytocin Reduces Seizure Burden and Hippocampal Injury in a Rat Model of Perinatal Asphyxia

Abstract

Context. Foetal asphyxia, a frequent birth complication, detrimentally impacts the immature brain, resulting in neuronal damage, uncontrolled seizure activity and long-term neurological deficits. Oxytocin, a neurohormone mediating important materno-foetal interactions and parturition, has been previously suggested to modulate the immature brain's excitability, playing a neuroprotective role. Our aim was to investigate the effects of exogenous oxytocin administration on seizure burden and acute brain injury in a perinatal model of asphyxia in rats. Animals and methods. Asphyxia was modelled by exposing immature rats to a 90-minute episode of low oxygen (9% O 2) and high CO 2 (20% CO 2). Control rats were kept in ambient room-air for the same time interval. In a third group of experiments, oxytocin (0.02 UI/g body weight) was nasally administered 30 minutes before the asphyxia episode. Seizure burden was assessed by the cumulative number of loss of righting reflex (LRR) over a two-hour postexposure period. Acute brain injury was assessed through hippocampal S-100 beta, a biomarker of cellular injury, 24-hours after exposure. Results. Asphyxia increased both LRR and hippocampal S-100 beta protein compared to controls, and these effects were significantly reduced by oxytocin administration. Conclusion. Oxytocin treatment decreased both seizure burden and hippocampal injury, supporting a potential neuroprotective role for oxytocin in perinatal asphyxia.

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

“…This was followed by an almost linear and much slower (0.0086 pH units/min) secondary recovery phase lasting until 15 min post-asphyxia. We did not observe an alkaline overshoot of the kind described in P6 rats with steady asphyxia induced by 9 % O 2 and 20 % CO 2 (Helmy et al, 2012(Helmy et al, , 2011, suggesting that fast brain pH recovery in itself is sufficient in triggering seizures following asphyxia (see also Panaitescu et al, 2018).…”

Plasmatic Levels of Neuropeptides, Including Oxytocin, in Children with Autism Spectrum Disorder, Correlate with the Disorder Severity

“…Given the higher plasma values observed in children with milder forms of ASDs, it may be hypothesised that their increased responsiveness to the behavioural therapy might be, at least partly, mediated through oxytocinergic mechanisms (46). Oxytocin's involvement in the GABA-switch from excitatory to inhibitory neurotransmitter at birth might substantiate the importance of its appropriate regulation for typical brain development (47,48). The correlations observed with other neuropeptide levels suggest that these substances might be inter-connected in terms of potential effectiveness in the administration of adjuvant treatment.…”

Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation

“…As such, preserving a low [Cl − ] i could be associated with higher cellular viability. We have previously shown that chloride transport modulation in immature hippocampal cultures has a neuroprotective effect both in vitro during OGD [24], as well as in an in vivo model of perinatal asphyxia [25]. Considering that mature neurons display altered chloride gradients under stroke conditions, which may also be influenced by many pharmaceutical agents used in stroke patients, there is an increased interest to determine the potentially favorable or detrimental effects of modulating chloride gradients.…”