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Propofol Attenuates Isoflurane-Induced Neurotoxicity and Cognitive Impairment in Fetal and Offspring Mice.
- Source :
-
Anesthesia and analgesia [Anesth Analg] 2020 Nov; Vol. 131 (5), pp. 1616-1625. - Publication Year :
- 2020
-
Abstract
- Background: Anesthesia in pregnant rodents causes neurotoxicity in fetal and offspring rodents. However, the underlying mechanisms and targeted treatments remain largely to be determined. Isoflurane and propofol are among commonly used anesthetics. Thus, we set out to investigate whether propofol can mitigate the isoflurane-induced neurotoxicity in mice.<br />Methods: Pregnant C57BL/6 mice at gestational day 15 (G15) were randomly assigned to 4 groups: control, isoflurane, propofol, and isoflurane plus propofol. Levels of interleukin (IL)-6 and poly-ADP ribose polymerase (PARP) fragment were measured in the brains of G15 embryos, and levels of postsynaptic density (PSD)-95 and synaptophysin were determined in the hippocampal tissues of postnatal day 31 (P31) offspring using Western blotting and immunohistochemical staining. Learning and memory functions in P31 offspring were determined using a Morris water maze test.<br />Results: Isoflurane anesthesia in pregnant mice at G15 significantly increased brain IL-6 (222.6% ± 36.45% vs 100.5% ± 3.43%, P < .0001) and PARP fragment (384.2% ± 50.87% vs 99.59% ± 3.25%, P < .0001) levels in fetal mice and reduced brain PSD-95 (30.76% ± 2.03% vs 100.8% ± 2.25%, P < .0001) and synaptophysin levels in cornu ammonis (CA) 1 region (57.08% ± 4.90% vs 100.6% ± 2.20%, P < .0001) and dentate gyrus (DG; 56.47% ± 3.76% vs 99.76% ± 1.09%, P < .0001) in P31 offspring. Isoflurane anesthesia also impaired cognitive function in offspring at P31. Propofol significantly mitigated isoflurane-induced increases in brain IL-6 (117.5% ± 10.37% vs 222.6% ± 36.45%, P < .0001) and PARP fragment (205.1% ± 35.99% vs 384.2% ± 50.87%, P < .0001) levels in fetal mice, as well as reductions in PSD-95 (49.79% ± 3.43% vs 30.76% ± 2.03%, P < .0001) and synaptophysin levels in CA1 region (85.57% ± 2.97% vs 57.08% ± 4.90%, P < .0001) and DG (85.05% ± 1.87% vs 56.47% ± 3.76%, P < .0001) in hippocampus of P31 offspring. Finally, propofol attenuated isoflurane-induced cognitive impairment in offspring.<br />Conclusions: These findings suggest that gestational isoflurane exposure in mice induces neuroinflammation and apoptosis in embryos and causes cognitive impairment in offspring. Propofol can attenuate these isoflurane-induced detrimental effects.
- Subjects :
- Animals
Animals, Newborn
Brain Chemistry drug effects
CA1 Region, Hippocampal drug effects
CA1 Region, Hippocampal metabolism
Cognitive Dysfunction psychology
Disks Large Homolog 4 Protein metabolism
Female
Fetus
Interleukin-6 metabolism
Maze Learning
Mice
Mice, Inbred C57BL
Poly (ADP-Ribose) Polymerase-1 metabolism
Pregnancy
Synaptophysin metabolism
Anesthetics, Inhalation toxicity
Anesthetics, Intravenous pharmacology
Cognitive Dysfunction chemically induced
Cognitive Dysfunction prevention & control
Isoflurane antagonists & inhibitors
Isoflurane toxicity
Nervous System Diseases chemically induced
Nervous System Diseases prevention & control
Propofol pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1526-7598
- Volume :
- 131
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Anesthesia and analgesia
- Publication Type :
- Academic Journal
- Accession number :
- 33079886
- Full Text :
- https://doi.org/10.1213/ANE.0000000000004955