Neurodegeneration in Newborn Rats Following Propofol and Sevoflurane Anesthesia

被引:111
作者
Bercker, Sven [1 ]
Bert, Bettina [2 ]
Bittigau, Petra
Felderhoff-Mueser, Ursula [3 ]
Buehrer, Christoph [4 ]
Ikonomidou, Chrysanthy [5 ]
Weise, Mirjam [6 ]
Kaisers, Udo X. [1 ]
Kerner, Thoralf [6 ]
机构
[1] Univ Hosp Leipzig, Dept Anesthesiol & Intens Care Med, Leipzig, Germany
[2] Free Univ Berlin, Inst Pharmacol & Toxicol, Sch Vet Med, D-1000 Berlin, Germany
[3] Univ Hosp Essen, Dept Neonatol, Essen, Germany
[4] Charite, Childrens Hosp, Dept Neonatol, Campus Virchow Klinikum, D-13353 Berlin, Germany
[5] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA
[6] Asklepios Klinikum Hamburg, Dept Anesthesiol & Intens Care Med, Hamburg, Germany
关键词
Neurotoxicity; Propofol; Sevoflurane; Newborn; Anesthesia; Behavior; Histology; Rodents; APOPTOTIC NEURODEGENERATION; NEUROLOGICAL SEQUELAE; ANTIEPILEPTIC DRUGS; FETAL EXPOSURE; ISOFLURANE; NEUROAPOPTOSIS; CHILDREN; AGENTS; BRAIN; HABITUATION;
D O I
10.1007/s12640-009-9063-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:140 / 147
页数:8
相关论文
共 31 条
[1]   Anesthetic agents and the immature brain: Are these toxic or therapeutic? [J].
Anand, KJS ;
Phil, D ;
Soriano, SG .
ANESTHESIOLOGY, 2004, 101 (02) :527-530
[2]   Fischer 344 and Wistar rats differ in anxiety and habituation but not in water maze performance [J].
Bert, B ;
Fink, H ;
Huston, JP ;
Voits, M .
NEUROBIOLOGY OF LEARNING AND MEMORY, 2002, 78 (01) :11-22
[3]   Antiepileptic drugs and apoptosis in the developing brain [J].
Bittigau, P ;
Sifringer, M ;
Ikonomidou, C .
NEUROPROTECTIVE AGENTS, 2003, 993 :103-114
[4]   Antiepileptic drugs and apoptotic neurodegeneration in the developing brain [J].
Bittigau, P ;
Sifringer, M ;
Genz, K ;
Reith, E ;
Pospischil, D ;
Govindarajalu, S ;
Dzietko, M ;
Pesditschek, S ;
Mai, I ;
Dikranian, K ;
Olney, JW ;
Ikonomidou, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :15089-15094
[5]   Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain [J].
Cattano, Davide ;
Young, Chainllie ;
Straiko, Megan M. W. ;
Olney, John W. .
ANESTHESIA AND ANALGESIA, 2008, 106 (06) :1712-1714
[6]   IMPROVED CUPRIC-SILVER METHOD FOR IMPREGNATION OF AXONAL AND TERMINAL DEGENERATION [J].
DEOLMOS, JS ;
INGRAM, WR .
BRAIN RESEARCH, 1971, 33 (02) :523-&
[7]   PHENOBARBITAL FOR FEBRILE SEIZURES - EFFECTS ON INTELLIGENCE AND ON SEIZURE RECURRENCE [J].
FARWELL, JR ;
LEE, YJ ;
HIRTZ, DG ;
SULZBACHER, SI ;
ELLENBERG, JH ;
NELSON, KB .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (06) :364-369
[8]   Neonatal exposure to a combination of N-methyl-D-aspartate and γ-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent Behavioral deficits [J].
Fredriksson, Anders ;
Ponten, Emma ;
Gordh, Torsten ;
Eriksson, Per .
ANESTHESIOLOGY, 2007, 107 (03) :427-436
[9]   SOME NEW, SIMPLE AND EFFICIENT STEREOLOGICAL METHODS AND THEIR USE IN PATHOLOGICAL RESEARCH AND DIAGNOSIS - REVIEW ARTICLE [J].
GUNDERSEN, HJG ;
BENDTSEN, TF ;
KORBO, L ;
MARCUSSEN, N ;
MOLLER, A ;
NIELSEN, K ;
NYENGAARD, JR ;
PAKKENBERG, B ;
SORENSEN, FB ;
VESTERBY, A ;
WEST, MJ .
APMIS, 1988, 96 (05) :379-394
[10]   Sevoflurane potentiates and blocks GABA-induced currents through recombinant α1ß2γ2 GABAA receptors:: implications for an enhanced GABAergic transmission [J].
Hapfelmeier, G ;
Schneck, H ;
Kochs, E .
EUROPEAN JOURNAL OF ANAESTHESIOLOGY, 2001, 18 (06) :377-383