title: Erythropoietin attenuates isoflurane-induced neurodegeneration and learning deficits in the developing mouse brain.
abstract: OBJECTIVE
  To examine whether recombinant erythropoietin (rEPO) attenuates neurodegeneration and the learning disability induced by isoflurane with the postnatal day 7 (P7) mice.
  
  
  BACKGROUND
  Some of general anesthetic agents induce neurodegeneration in developing brain. Several drugs, but not rEPO, were reported as candidates for the prevention of or treatment for neurodegeneration.
  
  
  METHODS
  We divided P7 mice into three groups at random. One group (IE group) was exposed to 6-h isoflurane (1.0%) after 50,000 IU·kg(-1) rEPO administered subcutaneously. The second group (I) was exposed to isoflurane in the same manner as IE group except saline instead of rEPO. The third group (E) was exposed to air after rEPO administered. The mice were assigned to the radial arm maze on four consecutive days from P56 (day 1) to P59 (day 4). We divided the number of errors each day by that of day 1 to establish each-day performance ratio. After the test, neurodegenerative change in the hilus of dentate gyrus was assessed using Nissl staining.
  
  
  RESULTS
  In radial maze test, the performance ratios of day 3 (mean ± sd) were 0.3 ± 0.2 (P < 0.05, vs I group), 0.8 ± 0.5, and 0.6 ± 0.2 in IE, I, and E groups, respectively, while those of day 4 were 0.3 ± 0.1 (P < 0.05), 0.8 ± 0.5, and 0.3 ± 0.2 (P < 0.05), respectively. The histopathological study revealed that in IE group the degenerative neuronal change was attenuated compared with I group.
  
  
  CONCLUSIONS
  These results suggested that rEPO attenuated isoflurane-induced neurodegeneration.
authors.affiliation: Division of Anesthesiology and Perioperative Medicine, Kobe University Graduate School of Medicine, Chuo-Ku, Kobe, Japan. teppei1002@gmail.com
authors.forename: Teppei
authors.initials: T
authors.lastname: Tsuchimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Jun
authors.initials: J
authors.lastname: Morishita
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Maekawa
mesh_terms: D000388:Air; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D007530:Isoflurane / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000517:prevention & control*; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D018685:Anesthetics, Inhalation; D004921:Erythropoietin; D012965:Sodium Chloride; D007530:Isoflurane