Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats

Arthur S. Leitzke, William B. Rolland, Paul R. Krafft, Tim Lekic, Damon Klebe, Jerry J. Flores, Nicole R. Van Allen, Richard Lee Applegate, John H. Zhang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


BACKGROUND AND PURPOSE - 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.

Original languageEnglish (US)
Pages (from-to)3587-3590
Number of pages4
Issue number12
StatePublished - Dec 2013
Externally publishedYes


  • Apoptosis
  • Caspase-3
  • Isoflurane
  • Sphingosine kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing


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