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Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia.

Seehase M, Jennekens W, Zwanenburg A, Andriessen P, Collins JJ, Kuypers E, Zimmermann LJ, Vles JSh, Gavilanes AW, Kramer BW - Mol Cell Pediatr (2015)

Bottom Line: UCO resulted in global asphyxia and cardiac arrest.Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.

ABSTRACT

Background: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.

Methods: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.

Results: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.

Conclusions: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

No MeSH data available.


Related in: MedlinePlus

EEG analysis. Pre- and postnatal EEG of control groups and EEG before, during, and after UCO in asphyxia groups. Depicted are (A) the median burst per minute, (B) the median total spectral power, (C) the relative spectral power for δ1, and (D) the interburst interval length as median and interquartile range. Significant differences (p < 0.05) are marked by (*). UCO, umbilical cord occlusion; IBI, interburst interval.
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Fig3: EEG analysis. Pre- and postnatal EEG of control groups and EEG before, during, and after UCO in asphyxia groups. Depicted are (A) the median burst per minute, (B) the median total spectral power, (C) the relative spectral power for δ1, and (D) the interburst interval length as median and interquartile range. Significant differences (p < 0.05) are marked by (*). UCO, umbilical cord occlusion; IBI, interburst interval.

Mentions: Figure 2 illustrates the aEEG trace before, during, and after the UCO. During baseline condition, the lower margin amplitude is >10 μV and the upper margin amplitude is <25 μV, consistent with a normal background pattern of the brain. During baseline conditions, the median bursts per minute, the median total spectral power, the relative spectral power estimates, and the median SEF values were not different between the four experimental groups (Figure 3).Figure 2


Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia.

Seehase M, Jennekens W, Zwanenburg A, Andriessen P, Collins JJ, Kuypers E, Zimmermann LJ, Vles JSh, Gavilanes AW, Kramer BW - Mol Cell Pediatr (2015)

EEG analysis. Pre- and postnatal EEG of control groups and EEG before, during, and after UCO in asphyxia groups. Depicted are (A) the median burst per minute, (B) the median total spectral power, (C) the relative spectral power for δ1, and (D) the interburst interval length as median and interquartile range. Significant differences (p < 0.05) are marked by (*). UCO, umbilical cord occlusion; IBI, interburst interval.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530565&req=5

Fig3: EEG analysis. Pre- and postnatal EEG of control groups and EEG before, during, and after UCO in asphyxia groups. Depicted are (A) the median burst per minute, (B) the median total spectral power, (C) the relative spectral power for δ1, and (D) the interburst interval length as median and interquartile range. Significant differences (p < 0.05) are marked by (*). UCO, umbilical cord occlusion; IBI, interburst interval.
Mentions: Figure 2 illustrates the aEEG trace before, during, and after the UCO. During baseline condition, the lower margin amplitude is >10 μV and the upper margin amplitude is <25 μV, consistent with a normal background pattern of the brain. During baseline conditions, the median bursts per minute, the median total spectral power, the relative spectral power estimates, and the median SEF values were not different between the four experimental groups (Figure 3).Figure 2

Bottom Line: UCO resulted in global asphyxia and cardiac arrest.Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.

ABSTRACT

Background: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.

Methods: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.

Results: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.

Conclusions: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

No MeSH data available.


Related in: MedlinePlus