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.

该奖项将支持我们对神经胶质细胞中疤痕形成的机制的理解的工作。中枢神经系统的伤害通常会导致终身残疾。脊髓损伤或脑外伤的患者可能会严重丧失功能。像体内其他区域一样，受伤后中枢神经组织的机械刚度也会变化。这会影响传输信号的神经元以及支持大脑和脊髓中的细胞类型，这些神经元称为神经胶质细胞。一种称为星形胶质细胞的神经胶质细胞有助于形成神经胶质疤痕。疤痕抑制了受伤后功能恢复所需的神经元的再生。当前，组织动态变化的刚度对星形胶质细胞功能的影响尚不清楚。用这项赠款完成的工作将使用磁性改变星形胶质细胞周围环境的刚度，以了解细胞如何促进神经胶质疤痕的形成。最终，这些结果可能会导致脊髓损伤后恢复功能的新治疗方法。此外，该研究将补充一项名为“科学和运动”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性的方式。磁性活性水凝胶为三维微环境提供了一种新的方法来询问时间和空间变化的机械性能。变化是快速和可逆的，研究表明细胞迅速（在几秒钟内）迅速对机械性能的改变响应。实验将表征使用离体切片模型挫伤损伤后脊髓机械性能的动态变化，然后使用磁性活性水凝胶模仿体外这些变化以询问星形胶质细胞机制。实验将集中在星形胶质细胞的转录组变化上，以便更好地了解形成神经胶质疤痕的机制。这些研究将涉及粘弹性机制的临时梯度和空间梯度，这是由离体脊髓损伤模型的机械测试结果所启示的。总体而言，这项工作将提高我们对星形胶质细胞机制的理解，并有可能导致修复脊髓损伤的新治疗方法。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响评估标准来评估值得支持。