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Isoflurane preconditioning inhibits the effects of tissue-type plasminogen activator on brain endothelial cell in an in vitro model of ischemic stroke

Authors
 So Yeong Cheon  ;  So Yeon Kim  ;  Eun Hee Kam  ;  Jae Hoon Lee  ;  Jeong Min Kim  ;  Eun Jung Kim  ;  Tae Whan Kim  ;  Bon-Nyeo Koo 
Citation
 International Journal of Medical Sciences, Vol.14(5) : 425-433, 2017 
Journal Title
 International Journal of Medical Sciences 
Issue Date
2017
MeSH
Animals ; Apoptosis/drug effects ; Brain Injuries/complications ; Brain Injuries/drug therapy* ; Brain Injuries/genetics ; Brain Injuries/pathology ; Brain Ischemia/complications ; Brain Ischemia/drug therapy* ; Brain Ischemia/genetics ; Brain Ischemia/pathology ; Culture Media, Conditioned ; Cyclooxygenase 2/genetics ; Disease Models, Animal ; Endothelial Cells/drug effects ; Endothelial Cells/pathology ; Glucose/metabolism ; Humans ; Intracranial Hemorrhages/chemically induced ; Intracranial Hemorrhages/drug therapy ; Intracranial Hemorrhages/genetics ; Intracranial Hemorrhages/pathology ; Isoflurane/administration & dosage* ; Matrix Metalloproteinase 2/genetics ; Mice ; NF-kappa B/genetics ; Neurons/drug effects ; Neurons/pathology ; Oxygen/metabolism ; Receptors, LDL/genetics ; Stroke/drug therapy* ; Stroke/genetics ; Stroke/pathology ; Tissue Plasminogen Activator/administration & dosage* ; Tissue Plasminogen Activator/adverse effects ; Tissue Plasminogen Activator/genetics ; Tumor Suppressor Proteins/genetics
Keywords
Tissue-type plasminogen activator ; endothelial cell ; isoflurane ; matrix metalloproteinase ; neuronal cell ; oxygen/glucose deprivation
Abstract
Tissue-type plasminogen activator (tPA) is the only treatment for ischemic stroke. However, tPA could induce the intracranial hemorrhage (ICH), which is the main cause of death in ischemic stroke patient after tPA treatment. At present, there is no treatment strategy to ameliorate tPA-induced brain injury after ischemia. Therefore, we investigated the effect of pre-treated isoflurane, which is a volatile anesthetic and has beneficial effects on neurological dysfunction, brain edema and infarct volume in ischemic stroke model. In this study, we used oxygen/glucose deprivation and reperfusion (OGD/R) condition to mimic an ischemic stroke in vitro. Matrix metalloproteinases (MMP) activity was measured in endothelial cell media. Also, neuronal cell culture was performed to investigate the effect of pretreated isoflurane on the neuronal cell survival after tPA-induced injury during OGD/R. Isoflurane pretreatment prevented tPA-induced MMP-2 and MMP-9 activity and suppressed tPA-triggered LRP/NF-κB/Cox-2 signaling after OGD/R. Neuronal cells, incubated with endothelial cell conditioned medium (EC-CM) after tPA + OGD/R, showed upregulation of pro-apoptotic molecules. However, neurons incubated with isoflurane-pretreated EC-CM showed increased anti-apoptotic molecules. Our findings suggest that isoflurane pretreatment could attenuate tPA-exaggerated brain ischemic injury, by reducing tPA-induced LRP/NF-κB/Cox-2 in endothelial cells, endothelial MMP-2 and MMP-9 activation, and subsequent pro-apoptotic molecule in neurons after OGD/R.
Files in This Item:
T201701536.pdf Download
DOI
10.7150/ijms.18037
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
구본녀(Koo, Bon-Nyeo) ORCID logo https://orcid.org/0000-0002-3189-1673
김소연(Kim, So Yeon) ORCID logo https://orcid.org/0000-0001-5352-157X
김은정(Kim, Eun Jung) ORCID logo https://orcid.org/0000-0002-5693-1336
김정민(Kim, Jeongmin) ORCID logo https://orcid.org/0000-0002-0468-8012
이재훈(Lee, Jae Hoon) ORCID logo https://orcid.org/0000-0001-6679-2782
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154361
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