title: Erythropoietin diminishes isoflurane-induced apoptosis in rat frontal cortex.
abstract: BACKGROUND
  During the brain growth spurt, anesthetic drugs can cause cellular and behavioral changes in the developing brain. The aim of this study was to determine the neuroprotective effect of erythropoietin after isoflurane anesthesia in rat pups.
  
  
  METHODS
  A total of 42, 7-day-old Wistar rats were divided into three groups. Control group (GC; n = 14): Rats breathed 100% oxygen for 6 h; Isoflurane group (GI; n = 14): Rats were exposed to 1.5% isoflurane in 100% oxygen for 6 h; Isoflurane + erythropoietin group (GIE; n = 14): 1000 IU·kg(-1) (intraperitoneal; IP) Erythropoietin was administered after isoflurane anesthesia. Each group was divided into two groups for pathology and learning and memory tests. Silver, caspase-3, and fluoro-jade C staining were used for detecting apoptotic cells in frontal cortex, striatum, hippocampus, thalamus, and amygdala. Morris water maze was used to evaluate learning and memory.
  
  
  RESULTS
  There was a significant increase in apoptotic cell count after isoflurane anesthesia in the frontal cortex when compared with control group (29.0 ± 9.27 vs 3.28 ± 0.75 [P = 0.002], 20.85 ± 10.94 vs 2.0 ± 0.81 [P = 0.002] and 24.57 ± 10.4 vs 5.14 ± 0.69 [P = 0.024] with silver, caspase-3, and fluoro-jade C staining, respectively). The apoptotic cell count in the frontal cortex was significantly higher in GIE than GC with caspase-3 staining (9.14 ± 3.13 vs 2.0 ± 0.81, P = 0.002). The apoptotic cell count in GIE was significantly reduced in the frontal cortex when compared with GI (4.0 ± 0.81 vs 29.0 ± 9.27 [P = 0.002], 9.14 ± 3.13 vs 20.85 ± 10.94 [P = 0.04] and 4.0 ± 1.63 vs 24.57 ± 10.4 [P = 0.012] with silver, caspase-3, and fluoro-jade C staining, respectively).
  
  
  CONCLUSIONS
  A total of 1000 IU·kg(-1) IP erythropoietin diminished isoflurane-induced neuroapoptosis. Further experimental studies have to be planned to reveal the optimal dose and timing of erythropoietin before adaptation to clinical practice.
authors.affiliation: Department of Anesthesiology and Reanimation, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Elvan
authors.initials: E
authors.lastname: Ocmen
authors.affiliation: Department of Anesthesiology and Reanimation, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Abdurrahim
authors.initials: A
authors.lastname: Derbent
authors.affiliation: Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Serap C
authors.initials: SC
authors.lastname: Micilli
authors.affiliation: Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Ulker
authors.initials: U
authors.lastname: Cankurt
authors.affiliation: Department of Physiology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Ilkay
authors.initials: I
authors.lastname: Aksu
authors.affiliation: Department of Physiology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Ayfer
authors.initials: A
authors.lastname: Dayi
authors.affiliation: Department of Laboratory Animal Science, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.affiliation: Department of Anesthesiology and Reanimation, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Necati
authors.initials: N
authors.lastname: Gokmen
mesh_terms: D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D004921:Erythropoietin / Q000494:pharmacology*; D007530:Isoflurane / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D007530:Isoflurane
keywords: apoptosis; erythropoietin; isoflurane; learning; memory; rats