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Astrocyte Mechanobiology Following Central Nervous System Injury Revealed By Magnetically Active Hydrogels

磁活性水凝胶揭示中枢神经系统损伤后的星形胶质细胞力学生物学

基本信息

批准号：
2223318
负责人：
Peter Galie
金额：
$ 29.92万
依托单位：
Rowan University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2223318&HistoricalAwards=false
关键词：
Astrocyte Mechanobiology Following Central Nervous

项目摘要

This award will support work to improve our understanding of the mechanisms underlying scar formation in glial cells. Injury to the central nervous system often results in life-long disability. Patients with spinal cord injury or traumatic brain injury may suffer severe loss of function. Like other regions in the body, the mechanical stiffness of central nervous tissue changes after an injury. This affects both the neurons that transmit signals as well as supporting cell types in the brain and spinal cord, which are called glial cells. One type of glial cell, called an astrocyte, contributes to the formation of a glial scar. The scar inhibits the regeneration of neurons needed for functional recovery following an injury. Currently, the effects of the dynamically changing stiffness of the tissue on the function of the astrocytes is unknown. The work done with this grant will alter the stiffness of astrocytes’ surroundings using magnetism to understand how the cells contribute to glial scar formation. Eventually, these results can lead to new treatments for restoring function following spinal cord injury. Additionally, the research will be supplemented with an early childhood education program called “Science and Movement” that will introduce children to the ways in which scientists and engineers use magnetism.Magnetically active hydrogels provide a new means to interrogate time and spatial varying mechanical properties in three-dimensional microenvironments. The changes are fast and reversible, and studies indicate that cells respond to the altered mechanical properties rapidly (within seconds). The experiments will characterize the dynamic changes to the mechanical properties of the spinal cord following contusion injury using an ex vivo slice model, and then use magnetically active hydrogels to mimic these changes in vitro to interrogate astrocyte mechanobiology. Experiments will focus on the transcriptomic changes of the astrocytes in order to better understand the mechanisms underlying the formation of a glial scar. These studies will involve both temporal and spatial gradients of viscoelastic mechanics, informed by the results of the mechanical testing of the ex vivo spinal cord injury model. Overall, this work will improve our understanding of astrocyte mechanobiology and potentially lead to new treatments to repair spinal cord injury.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项将支持提高我们对神经胶质细胞疤痕形成机制的理解的工作。中枢神经系统损伤常常导致终身残疾。脊髓损伤或脑外伤患者可能会严重丧失功能。与身体的其他区域一样，中枢神经组织的机械刚度在受伤后会发生变化。这会影响传输信号的神经元以及大脑和脊髓中的支持细胞类型（称为神经胶质细胞）。一种称为星形胶质细胞的神经胶质细胞有助于神经胶质疤痕的形成。疤痕会抑制受伤后功能恢复所需的神经元的再生。目前，组织硬度的动态变化对星形胶质细胞功能的影响尚不清楚。这笔资助完成的工作将利用磁性改变星形胶质细胞周围的硬度，以了解细胞如何促进神经胶质疤痕形成。最终，这些结果可能会带来恢复脊髓损伤后功能的新疗法。此外，该研究还将辅以一项名为“科学与运动”的幼儿教育计划，该计划将向儿童介绍科学家和工程师使用磁力的方式。磁活性水凝胶提供了一种新的方法来研究三维微环境中随时间和空间变化的机械特性。这些变化是快速且可逆的，研究表明细胞对改变的机械性能快速做出反应（几秒钟内）。该实验将使用离体切片模型来表征挫伤后脊髓机械特性的动态变化，然后使用磁性活性水凝胶在体外模拟这些变化，以探究星形胶质细胞的力学生物学。实验将重点关注星形胶质细胞的转录组变化，以便更好地了解神经胶质疤痕形成的机制。这些研究将涉及粘弹性力学的时间和空间梯度，并由离体脊髓损伤模型的机械测试结果提供信息。总的来说，这项工作将提高我们对星形胶质细胞力学生物学的理解，并有可能带来修复脊髓损伤的新疗法。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。