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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3587-3590 |
| Number of pages | 4 |
| Journal | Stroke |
| Volume | 44 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2013 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Caspase-3
- Isoflurane
- Sphingosine kinase
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Advanced and Specialized Nursing
Cite this
Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats. / Leitzke, Arthur S.; Rolland, William B.; Krafft, Paul R.; Lekic, Tim; Klebe, Damon; Flores, Jerry J.; Van Allen, Nicole R.; Applegate, Richard Lee; Zhang, John H.
In: Stroke, Vol. 44, No. 12, 12.2013, p. 3587-3590.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats
AU - Leitzke, Arthur S.
AU - Rolland, William B.
AU - Krafft, Paul R.
AU - Lekic, Tim
AU - Klebe, Damon
AU - Flores, Jerry J.
AU - Van Allen, Nicole R.
AU - Applegate, Richard Lee
AU - Zhang, John H.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspase-3
KW - Isoflurane
KW - Sphingosine kinase
UR - http://www.scopus.com/inward/record.url?scp=84889249914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84889249914&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.113.001988
DO - 10.1161/STROKEAHA.113.001988
M3 - Article
C2 - 24149004
AN - SCOPUS:84889249914
VL - 44
SP - 3587
EP - 3590
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 12
ER -