title: Blood -brain barrier disruption was less under isoflurane than pentobarbital anesthesia via a PI3K/Akt pathway in early cerebral ischemia.
abstract: One of the important factors altering the degree of blood-brain barrier (BBB) disruption in cerebral ischemia is the anesthetic used. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been reported to be involved in modulating BBB permeability and in isoflurane induced neuroprotection. This study was performed to compare the degree of BBB disruption in focal cerebral ischemia under isoflurane vs pentobarbital anesthesia and to determine whether inhibition of PI3K/Akt would affect the disruption in the early stage of focal cerebral ischemia. Permanent middle cerebral artery (MCA) occlusion was performed in rats under 1.4% isoflurane or pentobarbital (50mg/kg i.p.) anesthesia with controlled ventilation. In half of each group LY294002, which is a PI3K/Akt inhibitor, was applied on the ischemic cortex immediately after MCA occlusion. After one hour of MCA occlusion, the transfer coefficient (Ki) of14C-α-aminoisobutyric acid (14C-AIB) was determined to quantify the degree of BBB disruption. MCA occlusion increased the Kiboth in the isoflurane and pentobarbital anesthetized rats. However, the value of Kiwas lower under isoflurane (11.5±6.0μL/g/min) than under pentobarbital (18.3±7.1μL/g/min) anesthesia. The Kiof the contralateral cortex of the pentobarbital group was higher (+74%) than that of the isoflurane group. Application of LY294002 on the ischemic cortex increased the Ki(+99%) only in the isoflurane group. The degree of BBB disruption by MCA occlusion was significantly lower under isoflurane than pentobarbital anesthesia in the early stage of cerebral ischemia. Our data demonstrated the importance of choice of anesthetics and suggest that PI3K/Akt signaling pathway plays a significant role in altering BBB disruption in cerebral ischemia during isoflurane but not during pentobarbital anesthesia.
authors.affiliation: Department of Anesthesiology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ, 08901-1977, USA. Electronic address: chi@rwjms.rutgers.edu.
authors.forename: Oak Z
authors.initials: OZ
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ, 08901-1977, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Mellender
authors.affiliation: Department of Anesthesiology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ, 08901-1977, USA.
authors.forename: Geza K
authors.initials: GK
authors.lastname: Kiss
authors.affiliation: Department of Anesthesiology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ, 08901-1977, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, 08854, USA.
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Weiss
mesh_terms: D000758:Anesthesia; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism; D002867:Chromones; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D007530:Isoflurane / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009025:Morpholines; D010424:Pentobarbital / Q000009:adverse effects / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction
chemical_list: D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007530:Isoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010424:Pentobarbital
keywords: (14)C-α-aminoisobutyric acid; Blood-brain barrier; Focal cerebral ischemia; Isoflurane; PI3K/Akt; Pentobarbital