Abstract
BackgroundPropofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment.Methods6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120.ResultsWestern blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point.ConclusionExposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.
Highlights
Propofol (6,2 Diisopropylphenol) is widely used in paediatric anaesthesia
We focused on Open-Field test (OF) [21] and tests assessing activity and anxiety, Novel-Object-Recognition test (NOR) [22] assessing memory function
In thalamic brain regions we observed a significant increase in cleaved caspase-3 12 hrs after the last injection (log2FC(12 h) = 0.83, standard error (SE) = 0.26, t(28) = 2.92, q = 0.01)
Summary
In 1999 the US Federal Drug administration decreased the approved age for maintenance of anaesthesia with propofol to 2 months, whereas in Germany the use of propofol 1% for induction and maintenance of anaesthesia is approved for children older than 1 month [1]. Despite these off-label restrictions propofol administration is common for anaesthesia in newborns and young children, even in preterms. Data on long-term neurological outcome in children after propofol administration are missing. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment
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