Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space.
The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the second in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. We here build the bistable network model of brain ischemia. The central concept is that of a post-ischemic state space. Ischemia, as a quantitative perturbation, is envisioned to push the brain through a series of four phenotypes as a function of the amount of ischemia: the homeostatic, preconditioned, delayed neuronal death and necrotic phenotypes. The phenotypes are meta-stable attractors in the landscape of the post-ischemic state space. The sequence of the phenotypes derives from the mutual antagonism between damage mechanisms and stress responses, each conceived as aggregate ensemble variables. The competition between damage mechanisms and stress responses is posited to have the form of a bistability. Application of bistability to brain ischemia is grounded in the incontrovertible fact that post-ischemic neurons face the mutually exclusive decision to either live or die.
Department of Physiology, Wayne State University, Detroit, MI 48201, U.S.A.
Donald J
DJ
Degracia
J Cereb Blood Flow Metab. 2002 Nov;22(11):1283-96
12439285
Science. 2009 Jul 24;325(5939):429-32
19628860
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8697-702
16735474
Biophys J. 2004 May;86(5):2748-57
15111393
Cell Stress Chaperones. 2006 Spring;11(1):44-50
16572728
Metab Brain Dis. 1986 Sep;1(3):205-20
3508242
J Cell Physiol. 2009 Oct;221(1):10-7
19562686
Nat Med. 2008 May;14(5):497-500
18463660
Circulation. 1986 Dec;74(6 Pt 2):IV138-53
3536160
Mol Microbiol. 2006 Jul;61(1):165-84
16824103
Curr Opin Biotechnol. 2008 Oct;19(5):475-81
18804166
Dev Biol. 2007 May 15;305(2):695-713
17412320
Br J Anaesth. 1985 Jan;57(1):47-62
3917676
J Appl Physiol (1985). 1991 Oct;71(4):1185-95
1757340
Neuroscience. 2004;123(2):575-82
14698764
Ann Neurol. 2009 Feb;65(2):124-39
19260029
J Neurol Sci. 2000 Oct 1;179(S 1-2):1-33
11054482
Neuropathology. 2000 Sep;20 Suppl:S95-7
11037198
Blood. 2002 May 1;99(9):3089-101
11964270
Curr Biol. 2005 Dec 6;15(23):R961-3
16332526
Nat Neurosci. 2007 Nov;10(11):1369-76
17965657
Brain Pathol. 1994 Jan;4(1):59-65
8025703
Exp Cell Res. 2000 Nov 25;261(1):91-103
11082279
Arzneimittelforschung. 1991 Mar;41(3A):288-92
1859497
Biophys J. 2006 Aug 1;91(3):857-65
16648169
Bioessays. 2009 May;31(5):546-60
19319911
Curr Opin Biotechnol. 2008 Aug;19(4):381-8
18634875
Traffic. 2009 Apr;10(4):349-63
19183301