Enhanced Neuroprotection Following Acute SCI Using Fibrous Materials

使用纤维材料增强急性 SCI 后的神经保护

• 批准号: 9265525
• 负责人: Ryan J. Gilbert
• 金额: $ 26.54万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9265525
• 关键词: Acute; Affect; Animal Model; Animals; Area; Astrocytes; Attenuated; Axon; Behavior; Biocompatible Materials; Caliber; Cells; Characteristics; Chemicals; Chronic; Cicatrix; Clinical; Coculture Techniques; Contusions; Data; Development; Electrospinning; Engineering; Environment; Excitatory Amino Acid Transporter 2; Extracellular Matrix; Fiber; Frequencies; Gene Expression; Glial Fibrillary Acidic Protein; Glutamate Transporter; Glutamates; Heterogeneity; Hour; Implant; In Vitro; Inflammation; Injury; Laboratories; Lead; Lesion; Mechanics; Methods; Modeling; Molecular Profiling; Morphology; Motor Neurons; Mutation; Natural regeneration; Neuraxis; Neurites; Neurons; Neuropathy; Neurophysiology - biologic function; Outcome; Phenotype; Physiology; Procedures; Production; Proliferating; Rattus; Recovery of Function; Rodent Model; STAT3 gene; Scientist; Sensory; Severities; Shapes; Site; Specific qualifier value; Spinal Cord; Spinal Cord transection injury; Spinal cord injury; Stains; System; Testing; Time; Tissue Stains; Tissues; Up-Regulation; Viral; axon regeneration; central nervous system injury; excitotoxicity; experimental study; extracellular; interest; killings; migration; nanofiber; neuroprotection; phenotypic biomarker; public health relevance; response; response to injury; scaffold; spinal cord regeneration

 DESCRIPTION: Following spinal cord injury, secondary injury and the formation of a glial scar create an environment that does not foster axonal regeneration. Therefore, those sustaining spinal cord injury have some form of functional deficit below the level of injury. With increasing frequency, scientists and engineers are developing biomaterial scaffolds to help promote axonal regeneration into and through the lesion site. While no biomaterial strategy is used clinically, several strategies show promise within animal models of spinal cord injury. Recently, our group discovered that electrospun fiber scaffolds are able to facilitate robust regeneration of axons within a complete transection spinal cord injury model. Results from this study also demonstrated that astrocytes migrated extensively into the biomaterial conduct, instead of forming the typical glial scar that surrounds the lesion site. In this application, we seek to bettr understand astrocytic response to topography and uncover the possible mechanisms by which topographically changed astrocytes facilitate neuroprotection and axonal regeneration following acute spinal cord injury. Aims 1 and 2 of the application attempt to elucidate how astrocytes are phenotypically changed by fibers and if these phenotypic changes are altered by motor neuron presence. Additionally, we will examine the ability of these astrocytes to protect neurons from glutamate excitotoxicity. Lastly, in Aim 3, we will employ electrospun fibers within hemisection and contusive models of rat, acute SCI and examine astrocyte phenotypic changes, neuroprotective benefits and the ability of electrospun fibers to promote spinal cord regeneration and functional recovery. In conclusion, understanding the mechanisms by which biomaterials change astrocytes, in ways that support axonal regeneration, may lead to development of a biomaterial treatment option for those who suffer from acute spinal cord injury.

 描述：脊髓损伤后，继发性损伤和神经胶质疤痕的形成会产生不利于轴突再生的环境。因此，那些遭受脊髓损伤的人在损伤水平以下存在某种形式的功能缺陷。随着频率的增加，科学家和工程师正在开发生物材料支架，以帮助促进轴突再生进入和穿过病变部位。虽然临床上没有使用生物材料策略，但几种策略在脊髓损伤的动物模型中显示出了前景。最近，我们的小组发现电纺纤维支架能够在完全横断脊髓损伤模型中促进轴突的稳健再生。这项研究的结果还表明，星形胶质细胞广泛迁移到生物材料通道中，而不是形成病变部位周围的典型神经胶质疤痕。在本申请中，我们寻求更好地了解星形胶质细胞对地形的反应，并揭示地形改变的星形胶质细胞促进急性脊髓损伤后神经保护和轴突再生的可能机制。该申请的目标1和2试图阐明星形胶质细胞如何被纤维改变表型，以及这些表型改变是否因运动神经元的存在而改变。此外，我们将检查这些星形胶质细胞保护神经元免受谷氨酸兴奋毒性的能力。最后，在目标 3 中，我们将在大鼠半切和挫伤模型、急性 SCI 中使用电纺纤维，并检查星形胶质细胞表型变化、神经保护作用以及电纺纤维促进脊髓再生和功能恢复的能力。总之，了解生物材料以支持轴突再生的方式改变星形胶质细胞的机制，可能会为患有急性脊髓损伤的患者开发生物材料治疗方案。