Related Experiment Video
Updated: May 6, 2026
Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury
Published on: January 20, 2023
Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats
Arthur S Leitzke1, William B Rolland, Paul R Krafft
1From 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.
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.
Insights
Isoflurane post-treatment reduced neurological damage after germinal matrix hemorrhage (GMH) in rat pups. This effect is linked to activating the sphingosine kinase/Akt pathway, improving motor function and reducing brain swelling.
Area of Science:
- Neuroscience
- Anesthesiology
- Neonatal Research
Background:
- Germinal matrix hemorrhage (GMH) is a common cause of neurological deficits in premature infants.
- The precise mechanisms underlying GMH-induced neurological sequelae require further elucidation.
- Identifying therapeutic targets to mitigate GMH-related brain injury is critical.
Purpose of the Study:
- To investigate if isoflurane anesthesia can ameliorate neurological sequelae following germinal matrix hemorrhage (GMH).
- To determine if isoflurane exerts its neuroprotective effects via the sphingosine kinase/sphingosine-1-phosphate receptor/Akt pathway.
- To assess the impact of isoflurane on brain injury markers and functional outcomes in a rat model of GMH.
Main Methods:
- Germinal matrix hemorrhage (GMH) was induced in P7 rat pups using intraparenchymal collagenase infusion.
- Animals received 2% isoflurane post-surgery, either as a single dose or for 3 days.
- Isoflurane treatment was combined with antagonists for sphingosine-1-phosphate receptor (VPC23019) or sphingosine kinase (N,N-dimethylsphingosine).
Main Results:
- Isoflurane increased brain sphingosine kinase-1 and phosphorylated Akt expression, while decreasing cleaved caspase-3.
- These changes were reversed by sphingosine kinase and sphingosine-1-phosphate receptor antagonists.
- Isoflurane significantly reduced ventricular dilation and improved motor function, but not cognitive function, in GMH rats.
Conclusions:
- Post-treatment with isoflurane shows potential for improving neurological outcomes after germinal matrix hemorrhage.
- The neuroprotective effects of isoflurane appear to be mediated through the activation of the sphingosine kinase/Akt pathway.
- Further research is warranted to explore isoflurane as a therapeutic strategy for GMH.
