Factors Affecting Regeneration Through the Glial Scar

影响神经胶质疤痕再生的因素

• 批准号: 8606513
• 负责人: Jerry Silver
• 金额: $ 34万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8606513
• 关键词: Ablation; Adhesions; Adhesives; Adult; Affect; Afferent Neurons; Animals; Antibodies; Astrocytes; Axon; Behavior; Binding; Biological Assay; CSPG4 gene; Cell surface; Cells; Chondroitin Sulfate Proteoglycan; Chondroitinases; Chronic; Cicatrix; Coculture Techniques; Complex; Data; Distal; Enzymes; Extracellular Matrix; Failure; Family; Fibronectins; Fostering; Foundations; Genetic; Goals; Growth; Growth Cones; Hyaluronidase; Image; In Vitro; Inorganic Sulfates; Integrins; Knockout Mice; Label; Laminin; Lead; Lesion; Light; Mediating; Microscopy; Modeling; Mus; NG2 antigen; Natural regeneration; Neuroglia; Neurons; Peptides; Play; Population; Production; Proteoglycan; Rattus; Recovery of Function; Reporter; Resolution; Role; Sensory; Spinal cord injury; Spottings; Staging; Surface; Synapses; Techniques; Testing; Therapeutic; Time; Transgenic Mice; Traumatic CNS injury; Unspecified or Sulfate Ion Sulfates; aggrecan; axon regeneration; cell type; cohort; conditioning; dorsal column; extracellular; improved; in vitro Assay; in vivo; multi-photon; precursor cell; preference; receptor; research study; sciatic nerve; synaptogenesis; tissue fixing

DESCRIPTION (provided by applicant): According to the Christopher and Dana Reeve Foundation there are more than 1 million people with spinal cord injury (SCI) in the US. Developing strategies to promote regeneration and functional recovery after SCI has been a long and challenging goal. Although our lab was the first to recognize the critical role of sulfated proteoglycans in regeneration failure, the mechanisms by which the cells that produce this family of inhibitory extracellular matrix molecules block regeneration is largely unknown. Regenerating, albeit dystrophic, axons continually and tightly associate with a cohort of precursor cells in the core of the lesion that produce what is thought to be a potently inhibitory proteoglycan called NG2. The role of these NG2 cells and what has been purported to be a major proteoglycan in regeneration failure has become highly controversial. Our proposed studies will reveal for the first time how such highly preferred growth upon the surface of these cells results in an adhesive entrapment phenomenon that is likely to be a critical determinant in regeneration failure. Our proposed studies will also build upon the exciting discovery of a family of receptors on neurons that mediate, we propose via overly strong adhesive mechanisms, the inhibitory actions of CSPGs. Understanding in depth the complicated cellular and molecular interactions that lead to long term entrapment of axons within the glial scar will allow us to devise improved techniques for blocking or overcoming these untoward interactions and help in the search for strategies to stimulate robust regeneration beyond the glial scar.)

描述（由申请人提供）：根据克里斯托弗（Christopher）和达娜·里夫（Dana Reeve）基金会的说法，美国有超过100万人患有脊髓损伤（SCI）。在SCI之后制定促进再生和功能恢复的策略是一个漫长而挑战的目标。尽管我们的实验室是第一个认识到硫酸化蛋白聚糖在再生失败中的关键作用的人，但产生该抑制性细胞外基质分子封闭的细胞的机制在很大程度上是未知的。再生，尽管营养不良，但轴突不断地与病变核心中的一系列前体细胞紧密相关，这些细胞会产生被认为是一种有效的抑制性蛋白聚糖，称为NG2。这些NG2细胞的作用以及据称是再生衰竭中主要蛋白聚糖的主要蛋白酶已经变得极为争议。我们提出的研究将首次揭示这些细胞表面上如此高度首选的生长如何导致粘合性诱捕现象，这可能是再生失败的关键决定因素。我们提出的研究还将基于对介导的神经元家庭的令人兴奋的发现，我们通过过度强大的粘合剂机制（CSPG的抑制作用）提出。深入了解，复杂的细胞和分子相互作用导致长期缠绕在神经胶质疤痕中的轴突将使我们能够设计出改进的技术，以阻止或克服这些不受欢迎的相互作用，并有助于寻找策略，以刺激超出神经胶质疤痕以外的强大再生。