Enhanced Neuroprotection Following Acute SCI Using Fibrous Materials

 描述：脊髓损伤后，继发性损伤和胶质瘢痕的形成创造了一个不促进轴突再生的环境。因此，那些遭受脊髓损伤的人在损伤水平以下有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通过病变部位。虽然没有生物材料策略在临床上使用，但有几种策略在脊髓损伤的动物模型中显示出了希望。最近，我们的团队发现，电纺纤维支架能够在完整的脊髓横断损伤模型中促进轴突的强劲再生。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传导中，而不是形成围绕病变部位的典型胶质瘢痕。在这一应用中，我们试图更好地了解星形胶质细胞对地形的反应，并揭示地形变化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。申请的目标1和2试图阐明星形胶质细胞是如何通过纤维改变表型的，以及这些表型变化是否会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，我们将电纺纤维应用于大鼠急性脊髓损伤的半横断和挫伤模型，并检测星形胶质细胞的表型变化、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，可能会为那些遭受急性脊髓损伤的人开发一种生物材料治疗方案。

 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.