Cellular and molecular responses in human spinal cord injury

大量动物研究表明，神经胶质、内皮和间质反应是中枢神经系统(CNS)损伤的重要组成部分。然而，对脊髓损伤(SCI)后发生的细胞和分子反应知之甚少，并不是所有细胞的反应都来自体外研究，这些发现与体内条件的相关性，特别是在人类中，尚不清楚。本项目的目的是阐明胶质细胞(星形胶质细胞、小胶质细胞、少突胶质细胞、室管膜细胞)、雪旺细胞和间充质细胞(内皮细胞、中性粒细胞、巨噬细胞、脑膜细胞、成纤维细胞)在创伤所致的人脊髓损伤中的作用。这项研究的一个主要焦点将是识别“有益的”和“有害的”因素，即它们的细胞定位和时间分布。这些变化将与临床病程和治疗相关。迈阿密治疗瘫痪项目中大量的人类脊髓损伤病例的可获得性将促进这些关键数据的获得，这些数据可以作为未来动物研究的基础，以期改变损伤后的细胞和分子环境，拯救受损细胞，促进人类脊髓损伤后的轴突生长和再生。我们的一般假设是，基于来自体外研究和创伤致神经系统损伤的动物模型的现有数据，人类脊髓损伤诱导了各种神经胶质和间充质来源的动态平衡。炎症、神经营养和神经抑制因子，可能与损伤的持续时间或类型有关，并可能决定临床结果和治疗反应。

There is considerable evidence from animal studies that glial, endothelial and mesenchymal responses represent a prominent component of central nervous system (CNS) injury. However, little is known about the cellular and molecular responses that occur following spinal cord injury (SCI), and not all of the responses of cells have been obtained from in vitro studies, and the relevance of these findings to in vivo conditions, particularly in humans, is not known. The goal of this project is to clarify the role of glia (astrocytes, microglia, oligodendroglial, ependymal cells), Schwann cells and mesenchymal cells (endothelial cells, neutrophils, macrophages, meningeal cells, fibroblasts) in trauma-induced injury to the human spinal cord. A major focus of this study will be the identification of "beneficial" and "detrimental" factors, i.e., their cellular localization and temporal profile. The changes will be correlated with clinical course and therapy. The availability of an extensive bank of human cases of SCI in the Miami Project to Cure Paralysis will facilitate the acquisition of these critical data that can serve as the basis for future animal studies on potential strategies to alter the cellular and molecular environment following injury, to rescue damaged cells, and to promote axonal growth and regeneration in humans after SCI. Our general hypothesis, based on available data from in vitro studies, and animal models of trauma-induced injury to the nervous system, is that human SCI induces a variety of glial- and mesenchymal-derived homeostatic. inflammatory, neurotrophic and neuroinhibitory factors which may be related to the duration or type of injury, and may determine clinical outcome and response to therapy.