title: Emulsified Isoflurane Protects Against Transient Focal Cerebral Ischemia Injury in Rats via the PI3K/Akt Signaling Pathway.
abstract: BACKGROUND
  Phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathway activation may promote neuronal survival via neuroprotection during inflammation after cerebral ischemia. In this study, we investigated whether IV pretreatment with emulsified isoflurane (EI) could decrease ischemic brain injury related to the PI3K/Akt pathway.
  
  
  METHODS
  Male Sprague-Dawley rats received different doses of IV EI (1, 2, 4, or 8 mL/kg/h) or Intralipid (8 mL/kg/h) for 30 minutes (n = 6-12 per group), followed by middle cerebral artery occlusion (MCAO) for 100 minutes to induce transient focal ischemia. The neurologic score and infarct volume were measured 48 hours after MCAO. Immunostaining, Western blot analysis, and an enzyme-linked immunosorbent assay were used to assess EI effects on the cell inflammatory response, high-mobility group box-1 release, and phosphorylated Akt (expression. LY294002, a PI3K inhibitor, was also infused into the ventricular space before EI to determine the effect of EI.
  
  
  RESULTS
  Four milliliters per kilogram per hour of EI reduced the infarct size (21.08 ± 11.24 vs 37.09 ± 10.46, P = 0.006), improved neurologic scores after MCAO (1.13 ± 0.48 vs 1.95 ± 0.65, P = 0.015), significantly reinforced neuronal survival (982.7 ± 364.4 vs 439.8 ± 278.4, P = 0.036), and inhibited CD68 macrophage/macroglial infiltration in the ischemic core (188.2 ± 49.1 vs 282 ± 49.4, P = 0.018) compared with the vehicle group. In the EI pretreatment group, the serum high-mobility group box-1 concentration (3.62 ± 0.72 vs 5.73 ± 0.65, P < 0.001) was decreased, and the cerebral phosphorylated Akt level (50.33 ± 4.73 vs 37.5 ± 3.11, P = 0.007) was increased at 48 hours, which was inhibited by LY294002 compared with the vehicle group (5.31 ± 0.72 vs 5.73 ± 0.65, P = 0.216; 43.00 ± 4.84 vs 37.5 ± 3.11, P = 0.091).
  
  
  CONCLUSIONS
  These findings suggest that EI pretreatment protects against ischemic brain injury via the inhibition of cerebral inflammation and is associated with the PI3K-Akt pathway in rats with MCAO. This drug may be a novel therapeutic agent for patients after stroke.
authors: From the *Department of Anesthesiology and Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China; †Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic of China; ‡Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China; §Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China; ‖Department of Basic Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China; and ¶Department of Health Statistics, Forth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors: Hongfei
authors: H
authors: Zhang
authors: Xiaoxing
authors: X
authors: Xiong
authors: Jin
authors: J
authors: Liu
authors: Lijuan
authors: L
authors: Gu
authors: Fengxian
authors: F
authors: Li
authors: Yi
authors: Y
authors: Wan
authors: Shiyuan
authors: S
authors: Xu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D024243:HMGB1 Protein / Q000097:blood; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D007530:Isoflurane / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D004655:Emulsions; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018696:Neuroprotective Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D007530:Isoflurane; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt