Limits...
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

Western blot in frontal cortex of fetal brain. Western blot for (A) NMDA receptors, (B) pSTAT-3, (C) Bcl-xL, (D) cytochrome c, (E) cleaved caspase-9, and (F) cleaved caspase-3 in frontal cortex of fetal brain normalized to β-actin. Levels of the gestational age control group were set to 1 in all panels. Depicted are mean and SEM. Significant differences (p < 0.05) compared to gestational age control groups are marked by (*). Significant differences (p < 0.05) between asphyxiated and corresponding non-asphyxiated drug control group are marked by § and significant differences between asphyxiated propofol and asphyxiated isoflurane treated lambs are marked by ‡. NMDA-R, N-methyl-d-aspartate-receptor; GA, gestational age; pSTAT-3, phosphorylated signal transducer and activator of transcription-3; Bcl-xL, B-cell lymphoma-extra large; caspase, cysteinyl aspartate-specific protease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4530565&req=5

Fig5: Western blot in frontal cortex of fetal brain. Western blot for (A) NMDA receptors, (B) pSTAT-3, (C) Bcl-xL, (D) cytochrome c, (E) cleaved caspase-9, and (F) cleaved caspase-3 in frontal cortex of fetal brain normalized to β-actin. Levels of the gestational age control group were set to 1 in all panels. Depicted are mean and SEM. Significant differences (p < 0.05) compared to gestational age control groups are marked by (*). Significant differences (p < 0.05) between asphyxiated and corresponding non-asphyxiated drug control group are marked by § and significant differences between asphyxiated propofol and asphyxiated isoflurane treated lambs are marked by ‡. NMDA-R, N-methyl-d-aspartate-receptor; GA, gestational age; pSTAT-3, phosphorylated signal transducer and activator of transcription-3; Bcl-xL, B-cell lymphoma-extra large; caspase, cysteinyl aspartate-specific protease.

Mentions: In the propofol control group, the level of N-methyl-d-aspartate-receptor (NMDA-R) decreased to 31.5% ± 7.8% (p < 0.02) compared to the GA control group (Figure 5A). After prenatal asphyxia, NMDA-R levels decreased in propofol-treated lambs to 24.6% ± 6.6% (p = 0.04) compared to the GA controls and to 46.2% ± 21.7% (p < 0.05) when compared to the isoflurane asphyxia group.Figure 5


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)

Western blot in frontal cortex of fetal brain. Western blot for (A) NMDA receptors, (B) pSTAT-3, (C) Bcl-xL, (D) cytochrome c, (E) cleaved caspase-9, and (F) cleaved caspase-3 in frontal cortex of fetal brain normalized to β-actin. Levels of the gestational age control group were set to 1 in all panels. Depicted are mean and SEM. Significant differences (p < 0.05) compared to gestational age control groups are marked by (*). Significant differences (p < 0.05) between asphyxiated and corresponding non-asphyxiated drug control group are marked by § and significant differences between asphyxiated propofol and asphyxiated isoflurane treated lambs are marked by ‡. NMDA-R, N-methyl-d-aspartate-receptor; GA, gestational age; pSTAT-3, phosphorylated signal transducer and activator of transcription-3; Bcl-xL, B-cell lymphoma-extra large; caspase, cysteinyl aspartate-specific protease.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Western blot in frontal cortex of fetal brain. Western blot for (A) NMDA receptors, (B) pSTAT-3, (C) Bcl-xL, (D) cytochrome c, (E) cleaved caspase-9, and (F) cleaved caspase-3 in frontal cortex of fetal brain normalized to β-actin. Levels of the gestational age control group were set to 1 in all panels. Depicted are mean and SEM. Significant differences (p < 0.05) compared to gestational age control groups are marked by (*). Significant differences (p < 0.05) between asphyxiated and corresponding non-asphyxiated drug control group are marked by § and significant differences between asphyxiated propofol and asphyxiated isoflurane treated lambs are marked by ‡. NMDA-R, N-methyl-d-aspartate-receptor; GA, gestational age; pSTAT-3, phosphorylated signal transducer and activator of transcription-3; Bcl-xL, B-cell lymphoma-extra large; caspase, cysteinyl aspartate-specific protease.
Mentions: In the propofol control group, the level of N-methyl-d-aspartate-receptor (NMDA-R) decreased to 31.5% ± 7.8% (p < 0.02) compared to the GA control group (Figure 5A). After prenatal asphyxia, NMDA-R levels decreased in propofol-treated lambs to 24.6% ± 6.6% (p = 0.04) compared to the GA controls and to 46.2% ± 21.7% (p < 0.05) when compared to the isoflurane asphyxia group.Figure 5

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