DeGracia Donald J, Tri Anggraini Fika, Taha Doaa Taha Metwally, Huang Zhi-Feng
Department of Physiology, Wayne State University, 4116 Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA.
Department of Physics and Astronomy, Wayne State University, Detroit, MI 48201, USA.
Int Sch Res Notices. 2014 Oct 13;2014:859341. doi: 10.1155/2014/859341. eCollection 2014.
Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems.
许多具有临床相关性的急性损伤形式，如中风、创伤性脑损伤和心肌梗死，都难以找到预防损伤后细胞死亡的治疗方法。临床治疗的失败可能与目前基于损伤系统生物学特性的归纳模型有关。在此，我们对比了急性细胞损伤的归纳模型和演绎模型的应用。以脑缺血为例，我们讨论了归纳推理中的局限性，包括无法明确确定细胞死亡的因果关系以及缺乏系统的定量框架。这些局限性源于对损伤系统特有的定性分子途径的过度强调。我们最近开发的细胞损伤非线性动力学理论提供了一种通用的、系统的细胞损伤研究方法，其中吸引子状态和系统参数被用于定量表征急性损伤系统。我们讨论了转向演绎框架的理论、实证和治疗意义。我们说明了在开发急性损伤生物系统的治疗方法时，演绎数学框架相对于定性归纳模型如何具有切实的优势。
