title: Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats.
abstract: OBJECTIVE
  This study investigated whether isoflurane ameliorates neurological sequelae after germinal matrix hemorrhage (GMH) through activation of the cytoprotective sphingosine kinase/sphingosine-1-phosphate receptor/Akt pathway.
  
  
  METHODS
  GMH was induced in P7 rat pups by intraparenchymal infusion of bacterial collagenase (0.3 U) into the right hemispheric germinal matrix. GMH animals received 2% isoflurane either once 1 hour after surgery or every 12 hours for 3 days. Isoflurane treatment was then combined with sphingosine-1-phosphate receptor-1/2 antagonist VPC23019 or sphingosine kinase 1/2 antagonist N,N-dimethylsphingosine.
  
  
  RESULTS
  Brain protein expression of sphingosine kinase-1 and phosphorylated Akt were significantly increased after isoflurane post-treatment, and cleaved caspase-3 was decreased at 24 hours after surgery, which was reversed by the antagonists. Isoflurane significantly reduced posthemorrhagic ventricular dilation and improved motor, but not cognitive, functions in GMH animals 3 weeks after surgery; no improvements were observed after VPC23019 administration.
  
  
  CONCLUSIONS
  Isoflurane post-treatment improved the neurological sequelae after GMH possibly by activation of the sphingosine kinase/Akt pathway.
authors.affiliation: From the Department of Physiology and Pharmacology (A.S.L., W.B.R., P.R.K., T.L., D.K., J.J.F., N.R.V.A., J.H.Z.), and Department of Anesthesiology (A.S.L., R.L.A., J.H.Z.), Loma Linda University School of Medicine, CA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Leitzke
authors.forename: William B
authors.initials: WB
authors.lastname: Rolland
authors.forename: Paul R
authors.initials: PR
authors.lastname: Krafft
authors.forename: Tim
authors.initials: T
authors.lastname: Lekic
authors.forename: Damon
authors.initials: D
authors.lastname: Klebe
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Flores
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Van Allen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Applegate
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000099157:Sphingosine Kinase
chemical_list: D007530:Isoflurane; D018696:Neuroprotective Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); D051057:Proto-Oncogene Proteins c-akt; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C061800:N,N-dimethylsphingosine
keywords: apoptosis; caspase-3; isoflurane; sphingosine kinase