Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia.
Propofol and sevoflurane are commonly used drugs in pediatric anesthesia. Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. Newborn Wistar rats were treated with repeated intraperitoneal injections of propofol or sevoflurane inhalation and compared to controls. Brains were examined histopathologically using the De Olmos cupric silver staining. Additionally, a summation score of the density of apoptotic cells was calculated for every brain. Spatial memory learning was assessed by the Morris Water Maze (MWM) test and the hole board test, performed in 7 weeks old animals who underwent the same anesthetic procedure. Brains of propofol-treated animals showed a significant higher neurodegenerative summation score (24,345) when compared to controls (15,872) and to sevoflurane-treated animals (18,870). Treated animals also demonstrated persistent learning deficits in the hole board test, whereas the MWM test revealed no differences between both groups. Among other substances acting via GABAA agonism and/or NMDA antagonism propofol induced neurodegeneration in newborn rat brains whereas a sevoflurane based anesthesia did not. The significance of these results for clinical anesthesia has not been completely elucidated. Future studies have to focus on the detection of safe anesthetic strategies for the developing brain.
Bercker
Sven
S
Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany. sven.bercker@medizin.uni-leipzig.de
Bert
Bettina
B
Bittigau
Petra
P
Felderhoff-Müser
Ursula
U
Bührer
Christoph
C
Ikonomidou
Chrysanthy
C
Weise
Mirjam
M
Kaisers
Udo X
UX
Kerner
Thoralf
T
D000704:Analysis of Variance; D000777:Anesthetics / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis / Q000379:methods; D003463:Cues; D004305:Dose-Response Relationship, Drug; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000633:toxicity*; D009048:Motor Skills / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced*; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013028:Space Perception / Q000187:drug effects
D000777:Anesthetics; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol