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

Abstract

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.

• Authors: Arthur S Leitzke, William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Jerry J Flores, Nicole R Van Allen, Richard L Applegate 2nd, John H Zhang
• Journal: Stroke (Stroke) Vol. 44 Issue 12 Pg. 3587-90 (Dec 2013) ISSN: 1524-4628 [Electronic] United States
• PMID: 24149004 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Neuroprotective Agents
• Receptors, Lysosphingolipid
• Isoflurane
• Phosphotransferases (Alcohol Group Acceptor)
• sphingosine kinase
• Proto-Oncogene Proteins c-akt
• N,N-dimethylsphingosine
• Sphingosine

Topics

• Animals
• Animals, Newborn
• Brain (drug effects, metabolism)
• Disease Models, Animal
• Intracranial Hemorrhages (chemically induced, drug therapy, metabolism)
• Isoflurane (pharmacology, therapeutic use)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Phosphotransferases (Alcohol Group Acceptor) (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Receptors, Lysosphingolipid (metabolism)
• Recovery of Function (drug effects)
• Signal Transduction (drug effects)
• Sphingosine (analogs & derivatives, pharmacology, therapeutic use)