title: Cell death pathways in astrocytes with a modified model of oxygen-glucose deprivation.
abstract: Traditional oxygen-glucose deprivation (OGD) models do not produce sufficiently stable and continuous deprivation to induce cell death in the ischemic core. Therefore, we modified the OGD model to mimic the observed damage in the ischemic core following stroke and utilized this new model to study cell death pathways in astrocytes. The PO2 and pH levels in the astrocyte culture medium were compared between a physical OGD group, a chemical OGD group and a mixed OGD group. The mixed OGD group was able to maintain anaerobic conditions in astrocyte culture medium for 6 h, while the physical and the chemical groups failed to maintain such conditions. Astrocyte viability decreased and LDH release into in the medium increased as a function of exposure to OGD. Compared to the control group, the expression of active caspase-3 in the mixed OGD group increased within 2 h after OGD, but decreased after 2 h of OGD. Additionally, porimin mRNA levels did not significantly increase during the first 2 h of OGD, while bcl-2 mRNA levels decreased at 1 h. However, both porimin and bcl-2 mRNA levels increased after 2 h of OGD; interestingly, they both suddenly decreased at 4 h of OGD. Taken together, these results indicate that apoptosis and oncosis are the two cell death pathways responsible for astrocyte death in the ischemic core. However, the main death pathway varies depending on the OGD period.
authors: Department of Neurology, People's Hospital of Shenzhen City, Second Clinical College, Jinan University, Shenzhen, China.
authors: Qiaoying
authors: Q
authors: Huang
authors: Rui
authors: R
authors: Zhang
authors: Liang yu
authors: Ly
authors: Zou
authors: Xu
authors: X
authors: Cao
authors: Xiaofan
authors: X
authors: Chu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D011312:Pressure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D012972:Sodium Hydroxide / Q000494:pharmacology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012972:Sodium Hydroxide; D053148:Caspase 3; D005947:Glucose; D010100:Oxygen
references: Neurosci Lett. 2010 Jul 26;479(2):118-22
references: 20493926
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9778-83
references: 11481458
references: Neurotox Res. 2001 Apr;3(2):205-21
references: 14715474
references: Brain Res. 2007 May 29;1149:157-64
references: 17433269
references: Cancer Res. 1997 May 15;57(10):1835-40
references: 9157970
references: Eur J Neurosci. 2004 Sep;20(6):1514-24
references: 15355318
references: J Neurosci Methods. 1993 Mar;46(3):183-9
references: 8483311
references: Am J Physiol. 1989 Sep;257(3 Pt 1):C435-41
references: 2782387
references: J Physiol. 1990 May;424:387-409
references: 2391654
references: Int J Cancer. 2004 Mar 20;109(2):291-301
references: 14750183
references: Lancet Neurol. 2011 Apr;10(4):357-71
references: 21247806
references: Nat Rev Neurosci. 2006 Mar;7(3):194-206
references: 16495941
references: Toxicol Pathol. 1997 Jan-Feb;25(1):82-8
references: 9061857
references: Neuroreport. 1992 Dec;3(12):1135-7
references: 1493226
references: Cerebrovasc Dis. 2008;25(3):268-78
references: 18292653
references: Am J Pathol. 1995 Jan;146(1):3-15
references: 7856735
references: Clin Neurol Neurosurg. 2009 Jul;111(6):483-95
references: 19446389
references: Neurology. 1996 Oct;47(4):884-8
references: 8857713
references: Brain. 2008 Jan;131(Pt 1):218-28
references: 18084013
references: Nat Med. 1997 Jun;3(6):614-20
references: 9176486
references: Lancet Neurol. 2008 Oct;7(10):875-84
references: 18757238
references: J Neurosci. 1993 Aug;13(8):3510-24
references: 8101871
references: Neurosci Res. 2009 Jul;64(3):306-10
references: 19447300
references: Cell. 2003 Dec 26;115(7):863-77
references: 14697204
references: Cancer Chemother Pharmacol. 2011 Apr;67(4):813-21
references: 20563579
references: Physiol Rev. 1999 Oct;79(4):1431-568
references: 10508238