Article

Developmental Stage-dependent Persistent Impact of Propofol Anesthesia on Dendritic Spines in the Rat Medial Prefrontal Cortex

Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland.
Anesthesiology (Impact Factor: 6.17). 06/2011; 115(2):282-93. DOI: 10.1097/ALN.0b013e318221fbbd
Source: PubMed

ABSTRACT Recent observations demonstrate that anesthetics rapidly impair synaptogenesis during neuronal circuitry development. Whether these effects are lasting and depend on the developmental stage at which these drugs are administered remains, however, to be explored.
Wistar rats received propofol anesthesia at defined developmental stages during early postnatal life. The acute and long-term effects of these treatments on neuronal cytoarchitecture were evaluated by Neurolucida and confocal microscopy analysis after iontophoretic injections of Lucifer Yellow into layer 5 pyramidal neurons in the medial prefrontal cortex. Quantitative electron microscopy was applied to investigate synapse density.
Layer 5 pyramidal neurons of the medial prefrontal cortex displayed intense dendritic growth and spinogenesis during the first postnatal month. Exposure of rat pups to propofol at postnatal days 5 and 10 significantly decreased dendritic spine density, whereas this drug induced a significant increase in spine density when administered at postnatal days 15, 20, or 30. Quantitative electron microscopy revealed that the propofol-induced increase in spine density was accompanied by a significant increase in the number of synapses. Importantly, the propofol-induced modifications in dendritic spine densities persisted up to postnatal day 90.
These new results demonstrate that propofol anesthesia can rapidly induce significant changes in dendritic spine density and that these effects are developmental stage-dependent, persist into adulthood, and are accompanied by alterations in synapse number. These data suggest that anesthesia in the early postnatal period might permanently impair circuit assembly in the developing brain.

0 Followers
 · 
145 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Zahlreiche tierexperimentelle Untersuchungen zeigen, dass Anästhetika im unreifen Gehirn neurotoxisch wirken können, da sie Apoptose induzieren und die Neuro- sowie Synaptogenese beeinflussen. Im Tierexperiment hat dies erhebliche Auswirkungen auf die neurokognitiven Funktionen der Tiere im späteren Leben. Ob diese tierexperimentellen Ergebnisse auf den Menschen übertragen werden können, ist derzeit Gegenstand intensiver Forschung. In mehreren retrospektiven Untersuchungen konnte kein eindeutiger Zusammenhang zwischen einer Anästhesie im Früh-, Neugeborenen- oder Kleinkindalter und dem Auftreten von Lernstörungen oder Verhaltensauffälligkeiten gefunden werden. Zwei prospektive Studien (GAS und PANDA) sollen weiteren Einblick liefern und diese Frage möglichst klären. Wegen der großen Relevanz des Themas und um für die Problematik im Umgang mit den Eltern mehr Klarheit zu schaffen, haben der Wissenschaftliche Arbeitskreis für Kinderanästhesie und der Wissenschaftliche Arbeitskreis für Neuroanästhesie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) auf der Grundlage der derzeitigen Datenlage eine Stellungnahme verfasst ().
    Der Anaesthesist 02/2013; 62(2). DOI:10.1007/s00101-013-2139-0 · 0.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: New highly functionalized triazoloquinolines were synthesized by applying polar organometallic methods. Double metalation and functionalization provided 3,9-dihalogenated triazoloquinolines. Ring opening of the triazole with loss of nitrogen has been performed for the first time with 3,9-dihalogenated triazoloquinolines allowing the access toward 8-haloquinolin-2-carboxaldehydes under oxidant-free conditions. This approach demonstrates that the triazole ring can be used as protecting group of 2-quinolinecarboxaldehydes, activating the C9-position for lithiation and functionalization by triazole ring opening. 8-Haloquinoline-2-carbaldehydes become in this way readily available.Graphical abstract
    Tetrahedron 05/2009; 65(22):4410-4417. DOI:10.1016/j.tet.2009.03.058 · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anesthesia kills neurons in the brain of infantile animals, including primates, and causes permanent and progressive neurocognitive decline. The anesthesia community and regulatory authorities alike are concerned that is also true in humans. In this review, I summarize what we currently know about the risks of pediatric anesthesia to long-term cognitive function. If anesthesia is discovered to cause cognitive decline in humans, we need to know how to prevent and treat it. Prevention requires knowledge of the mechanisms of anesthesia-induced cognitive decline. This review gives an overview of some of the mechanisms that have been proposed for anesthesia-induced cognitive decline and discusses possible treatment options. If anesthesia induces cognitive decline in humans, we need to know what type and duration of anesthetic is safe, and which, if any, is not safe. This review discusses early results of comparative animal studies of anesthetic neurotoxicity. Until we know if and how pediatric anesthesia affects cognition in humans, a change in anesthetic practice would be premature, not guided by evidence of better alternatives, and therefore potentially dangerous. The SmartTots initiative jointly supported by the International Anesthesia Research Society and the Food and Drug Administration aims to fund research designed to shed light on these issues that are of high priority to the anesthesia community and the public alike and therefore deserves the full support of these interest groups.
    Anesthesia and analgesia 09/2011; 113(5):1170-9. DOI:10.1213/ANE.0b013e318232066c · 3.42 Impact Factor