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Tesi etd-07212007-185204


Thesis type
Tesi di dottorato di ricerca
Author
Cattano, Davide
email address
davidecattano@hotmail.com, cattanod@msnotes.wustl.edu
URN
etd-07212007-185204
Title
Propofol induces neuroapoptosis in the developing mouse brain
Settore scientifico disciplinare
BIO/14
Corso di studi
MORFOLOGIA E FUNZIONE NORMALE E PATOLOGICA DI CELLULE E TESSUTI
Commissione
Relatore Prof. Natale, Gianfranco
Parole chiave
  • programmed cell death
  • neurodevelopment
  • neuroapoptosis
  • neonatal age
  • brain spurt
  • anesthesia
  • propofol
Data inizio appello
09/07/2007;
Consultabilità
completa
Riassunto analitico
Drugs that suppress neuronal activity, including general anesthetics used in pediatric and obstetric medicine, trigger neuroapoptosis in the developing rodent brain. Brief exposure of infant mice to sub-anesthetic doses of any of several individual anesthetic drugs (ketamine, midazolam, isoflurane) triggers a significant neuroapoptosis response. Propofol, a general anesthetic currently being used with increasing frequency in pediatric and obstetric anesthesia, is a very effective suppressant of neuronal activity. Its mechanism of action is not fully understood; interaction with both GABAA receptors and NMDA glutamate receptors has been implicated. Propofol has not been evaluated for apoptogenic potential, either alone or in combination with other anesthetic agents. Therefore, we undertook the present study to determine whether propofol triggers neuroapoptosis in the infant mouse brain and, if so, what level of exposure is required to induce a significant neuroapoptosis response. In a dose-finding pilot study we determined that infant mice become unresponsive (loss of righting reflex) to deep pain (tail prick) at an intraperitoneal (ip) dose of approximately 200 mg/kg. A dose-response evaluation was then undertaken which revealed that any dose above 50 mg/kg ip induces a statistically significant neuroapoptosis response in several regions of the developing mouse brain. The magnitude of the response increased linearly in a dose dependent manner within the dose range tested (25 to 100 mg/kg ip). We conclude that a single sub-anesthetic (moderately sedating) dose of propofol triggers a significant neuroapoptosis response in the developing mouse brain.
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