title: Brain maturation in neonatal rodents is impeded by sevoflurane anesthesia.
abstract: BACKGROUND
  A wealth of data shows neuronal demise after general anesthesia in the very young rodent brain. Herein, the authors apply proton magnetic resonance spectroscopy (1HMRS), testing the hypothesis that neurotoxic exposure during peak synaptogenesis can be tracked via changes in neuronal metabolites.
  
  
  METHODS
  1HMRS spectra were acquired in the brain (thalamus) of neonatal rat pups 24 and 48 h after sevoflurane exposure on postnatal day (PND) 7 and 15 and in unexposed, sham controls. A repeated measure ANOVA was performed to examine whether changes in metabolites were different between exposed and unexposed groups. Sevoflurane-induced neurotoxicity on PND7 was confirmed by immunohistochemistry.
  
  
  RESULTS
  In unexposed PND7 pups (N = 21), concentration of N-acetylaspartate (NAA; [NAA]) increased by 16% from PND8 to PND9, whereas in exposed PND7 pups (N = 19), [NAA] did not change and concentration of glycerophosphorylcholine and phosphorylcholine ([GPC + PCh]) decreased by 25%. In PND15 rats, [NAA] increased from PND16 to PND17 for both the exposed (N = 14) and the unexposed (N = 16) groups. Two-way ANOVA for PND7 pups demonstrated that changes over time observed in [NAA] (P = 0.031) and [GPC + PCh] (P = 0.024) were different between those two groups.
  
  
  CONCLUSIONS
  The authors demonstrated that normal [NAA] increase from PND8 to PND9 was impeded in sevoflurane-exposed rats when exposed at PND7; however, not impeded when exposed on PND15. Furthermore, the authors showed that noninvasive 1HMRS is sufficiently sensitive to detect subtle differences in developmental time trajectory of [NAA]. This is potentially clinically relevant because 1HMRS can be applied across species and may be useful in providing evidence of neurotoxicity in the human neonatal brain.
authors.affiliation: From the Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York (R.M., H.L., Z.J., H.B.); Department of Applied Mathematics and Statistics (T.F.), Stony Brook University, Stony Brook, New York; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (J.-H.P., G.E.); and Department of Neurosurgery, Rochester University, Rochester, New York (M.N.).
authors.forename: Rany
authors.initials: R
authors.lastname: Makaryus
authors.forename: Hedok
authors.initials: H
authors.lastname: Lee
authors.forename: Tian
authors.initials: T
authors.lastname: Feng
authors.forename: June-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
authors.forename: Zvi
authors.initials: Z
authors.lastname: Jacob
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D005260:Female; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects*; D051381:Rats; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane