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Laser Thermal Immunomodulation in the Brain

大脑中的激光热免疫调节

基本信息

批准号：
570822-2021
负责人：
Klonisch, Thomas
金额：
$ 3.64万
依托单位：
University of Manitoba
依托单位国家：
加拿大
项目类别：
Alliance Grants
财政年份：
2021
资助国家：
加拿大
起止时间：
2021-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=723333
关键词：
Laser Thermal Immunomodulation Brain

项目摘要

Manitoba-based industry partner Monteris pioneered targeted laser thermal technology for selective tissue ablation in human brain and remains a market leader in minimally invasive precision NeuroBlate® laser technology. Emerging evidence suggests that laser thermal treatment can elicit novel immunomodulatory functions in the brain. Upon tissue placement of a thin optic fiber, laser thermal energy emitted from the optic fiber tip heat-coagulates tissue. Absorption of thermal load by surrounding tissue causes increasing heat dissipation away from the fiber tip. This laser thermal tissue gradient creates distinct histological regions with different degrees of tissue damage that range from a necrotic zone at the fiber tip to an edema zone farther from the tip. The laser thermal tissue gradient promotes an array of cellular and molecular responses that drive changes in cellular composition and activity in laser-treated brain. We will establish the first laser brain tumor mouse models in Canada and focus on a new role of laser thermal technology as a modulator of cellular immune activity in response to heat stress in brain. To understand the effects of laser-induced cellular immunomodulation on innate and adaptive immune cells in the brain environment, we study mouse brain models with pre-existing low/ moderate/ high cellular immune activation. We test the ability of two optic fiber designs on immunomodulation and generate tissue-based spatiotemporal high-resolution gene expression profiles mapped to laser-induced brain lesions. These tissue maps visualize immune cell composition/ activation along the laser thermal tissue gradient in distinct brain environments. This study inspires new designs and applications of laser technology for immunomodulation and sustains scientific partnership and HQP training for the advancement of future applications of NeuroBlate® laser technology.

位于马尼托巴省的行业合作伙伴NeuroBlate是用于人脑选择性组织消融的靶向激光热技术的先驱，并且仍然是微创精密NeuroBlate®激光技术的市场领导者。新出现的证据表明，激光热治疗可以引起大脑中的新的免疫调节功能。在薄光纤的组织放置时，从光纤尖端发射的激光热能热凝固组织。周围组织对热负荷的吸收导致远离光纤尖端的热耗散增加。该激光热组织梯度产生具有不同程度组织损伤的不同组织学区域，其范围从纤维尖端处的坏死区到远离尖端的水肿区。激光热组织梯度促进了一系列细胞和分子反应，这些反应驱动了激光治疗大脑中细胞组成和活性的变化。我们将在加拿大建立第一个激光脑肿瘤小鼠模型，并专注于激光热技术作为大脑热应激反应中细胞免疫活性调节剂的新作用。为了了解激光诱导的细胞免疫调节对脑环境中先天性和适应性免疫细胞的影响，我们研究了预先存在低/中/高细胞免疫激活的小鼠脑模型。我们测试了两种光纤设计对免疫调节的能力，并生成了映射到激光诱导的脑病变的基于组织的时空高分辨率基因表达谱。这些组织图显示了免疫细胞组成/激活沿着不同脑环境中的激光热组织梯度。这项研究激发了激光技术在免疫调节方面的新设计和应用，并为NeuroBlate®激光技术的未来应用提供了科学合作伙伴关系和HQP培训。