The influence of anesthetics on substantia nigra tyrosine hydroxylase expression and tau phosphorylation in the hypoxic–ischemic near-term lamb

Background General anesthetics could protect key neurotransmitter systems, such as the dopaminergic system, from hypoxic–ischemic encephalopathy (HIE) by limiting excessive glutamatergic neurotransmission. However, anesthetics may adversely affect inflammation and tau phosphorylation. Methods A near...

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Bibliographic Details
Published in:	Pediatric research Vol. 83; no. 6; pp. 1190 - 1199
Main Authors:	Barkhuizen, Melinda, van Dijck, Fleur J P, Jellema, Reint K, Gussenhoven, Ruth, Engelbertink, Imke, van Mechelen, Ralph, Cleutjens, Jack P M, Seehase, Matthias, Steinbusch, Harry W M, Zimmermann, Luc J, Gavilanes, A W Danilo, Kramer, Boris W
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-06-2018 Nature Publishing Group
Subjects:	Anesthetics - pharmacology Animals Animals, Newborn basic-science-investigation Brain damage Brain Mapping Dopamine - pharmacology Dopaminergic Neurons - drug effects Female Glutamine - metabolism Hippocampus - metabolism Hypoxia Hypoxia - metabolism Hypoxia-Ischemia, Brain - metabolism Inflammation Isoflurane - pharmacology Male Medicine Medicine & Public Health Mesencephalon - metabolism Microglia - metabolism Neurotransmitter Agents - metabolism Pediatric Surgery Pediatrics Phosphorylation Propofol - pharmacology Sheep Substantia Nigra - enzymology Synaptic Transmission tau Proteins - metabolism Tyrosine 3-Monooxygenase - metabolism Umbilical Cord - pathology
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Summary:	Background General anesthetics could protect key neurotransmitter systems, such as the dopaminergic system, from hypoxic–ischemic encephalopathy (HIE) by limiting excessive glutamatergic neurotransmission. However, anesthetics may adversely affect inflammation and tau phosphorylation. Methods A near-term sheep model of HIE by umbilical cord occlusion (UCO) under anesthesia was used. The effect of propofol and isoflurane on the dopaminergic neurotransmitter phenotype in the substantia nigra (SN) was studied using tyrosine hydroxylase immunohistochemistry. The overall microglial response and tau phosphorylation were also measured in the SN, surrounding the midbrain gray matter structures and the hippocampal white matter. Results The isoflurane-treated UCO group had fewer tyrosine hydroxylase-expressing neurons in the SN at 8 h after the insult than the propofol-treated UCO or sham-operated groups ( P <0.05). The microglial response was unchanged in the SN region. In the thalamus and the hippocampal stratum moleculare layer, the propofol-treated UCO group had a lower microglial response than the corresponding sham-operated group. Both UCO and the use of anesthetics additively increased tau phosphorylation in the SN region, thalamus, and hippocampus. Conclusion The choice of anesthetics is important for an emergency C-section. Propofol could potentially protect the dopaminergic neurotransmitter phenotype within the SN at the cost of a widespread increase in tau phosphorylation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0031-3998 1530-0447
DOI:	10.1038/pr.2018.42