Isoflurane Attenuates Blood—Brain Barrier Disruption in Ipsilateral Hemisphere After Subarachnoid Hemorrhage in Mice

• Published in: Stroke (1970) Vol. 43; no. 9; pp. 2513 - 2516
• Main Authors: ALTAY, Orhan, SUZUKI, Hidenori, HASEGAWA, Yu, CANER, Basak, KRAFFT, Paul R, FUJII, Mutsumi, JIPING TANG, ZHANG, John H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-09-2012
• Subjects: Anesthetics, Inhalation - therapeutic use; Animals; Biological and medical sciences; Biomarkers - analysis; Blood-Brain Barrier - drug effects; Blotting, Western; Brain Edema - pathology; Coloring Agents; Evans Blue; Functional Laterality - physiology; Isoflurane - therapeutic use; Male; Medical sciences; Mice; Neurology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors; Receptors, Lysosphingolipid - antagonists & inhibitors; Subarachnoid Hemorrhage - drug therapy; Subarachnoid Hemorrhage - physiopathology; Vascular diseases and vascular malformations of the nervous system; sphingosine-1-phosphate receptor; Cardiovascular disease; Blood brain barrier; Vascular disease; Cerebrovascular disease; Halogen Organic compounds; Volatile compound; blood-brain barrier; Stroke; Nervous system diseases; sphingosine kinase-1; Enzyme; Subarachnoid hemorrhage; Transferases; Rodentia; early brain injury; Isoflurane; Cerebral disorder; Vertebrata; Mammalia; General anesthetic; Mouse; Kinase; Animal; Central nervous system disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/strokeaha.112.661728

We examined effects of isoflurane, volatile anesthetics, on blood-brain barrier disruption in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice.
Animals were assigned to sham-operated, SAH+vehicle-air, SAH+1%, or 2% isoflurane groups. Neurobehavioral function, brain water content, Evans blue dye extravasation, and Western blotting for sphingosine kinases, occludin, claudin-5, junctional adhesion molecule, and vascular endothelial cadherin were evaluated at 24 hours post-SAH. Effects of sphingosine kinase (N,N-dimethylsphingosine) or sphingosine-1-phosphate receptor-1/3 (S1P1/3) inhibitors (VPC23019) on isoflurane's action were also examined.
SAH aggravated neurological scores, brain edema, and blood-brain barrier permeability, which were prevented by 2% but not 1% isoflurane posttreatment. Two percent isoflurane increased sphingosine kinase-1 expression and prevented a post-SAH decrease in expressions of the blood-brain barrier-related proteins. Both N,N-dimethylsphingosine and VPC23019 abolished the beneficial effects of isoflurane.
Two percent isoflurane can suppress post-SAH blood-brain barrier disruption, which may be mediated by sphingosine kinase 1 expression and sphingosine-1-phosphate receptor-1/3 activation.