Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space.
Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space.
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DOI：
10.6030/1939-067x-3.1.72
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发表时间：
2010
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影响因子：
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通讯作者：
Degracia DJ
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作者：
Degracia DJ
在缺血性中风的临床试验中，神经保护剂的普遍失败表明，在目前的缺血性脑损伤概念中可能存在一个根本的盲点，即“缺血级联反应”。这是一系列四篇论文中的第二篇，其目的是通过应用网络概念来开发脑缺血模型来修订脑缺血的概念。本文建立了脑缺血的神经网络模型。中心概念是缺血后状态空间。缺血，作为一种定量扰动，被设想为推动大脑通过一系列的四种表型作为缺血量的函数：稳态，预处理，迟发性神经元死亡和坏死表型。表型是缺血后状态空间景观中的亚稳定吸引子。表型的顺序来自损伤机制和应激反应之间的相互拮抗作用，每个被认为是聚合的合奏变量。损伤机制和应力响应之间的竞争被假定为具有双稳态的形式。应用双稳态研究脑缺血是基于缺血后神经元面临生存或死亡的互斥决定这一不争的事实。
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.