Nano-Pulsed Optoacoustic Neuromodulation for Reducing Traumatic Brain Injury-Driven Neuropathology and Improving Cognitive Outcome

纳米脉冲光声神经调节可减少创伤性脑损伤引起的神经病理学并改善认知结果

• 批准号: 10625431
• 负责人: RINAT O. ESENALIEV
• 金额: $ 50.58万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625431
• 关键词: Acute; Affect; Area; Biomedical Engineering; Brain; Brain Injuries; Brain Pathology; Cephalic; Chronic; Chronic Phase; Clinic; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Development; Diagnostic; Encephalitis; Evaluation; Eye; Frequencies; Goals; Hemoglobin; Hippocampus; Hour; Human; Impaired cognition; Inflammation; Injury; Institutional Review Boards; Lasers; Light; Low-Level Laser Therapy; Medical; Memory; Modeling; Monitor; Nerve Degeneration; Neurocognitive; Neurologic; Optics; Outcome; Pathology; Patients; Penetration; Phase; Physicians; Physiologic pulse; Pre-Clinical Model; Public Health; Publishing; Rattus; Research; Risk; Skin; Stress; Structure; System; TBI Patients; TBI treatment; Techniques; Technology; Translating; Traumatic Brain Injury; Travel; Treatment Efficacy; Work; absorption; brain tissue; care burden; chromophore; clinical application; cognitive change; disability; effective therapy; efficacy evaluation; expectation; fluid percussion injury; global health; improved; multidisciplinary; nano; nanosecond; nervous system disorder; neural circuit; neural stimulation; neurogenesis; neuroinflammation; neuronal circuitry; neuropathology; neuroprotection; neuroregulation; novel; pre-clinical; preservation; ultrasound

ABSTRACT Currently there are no effective treatments for the millions of traumatic brain injury (TBI) patients that are seen each year in US clinics; therefore, identifying and developing effective treatments remains an urgent, unmet need in public health. Our multidisciplinary team has developed a non-invasive, transcranial neuromodulation technique using nano-pulsed optoacoustic laser therapy (NPLT). Our proprietary system operates at levels of optical energy that are eye-safe and skin-safe, easy to deliver, and stress-free for the subject. This technology combines near-infrared laser light, which reduces brain inflammation and stimulates neuronal circuitry - but does not penetrate deeply into brain tissue - and optoacoustic waves, that also reduce inflammation and stimulate neural circuitry - yet they penetrate deeper into brain tissue, allowing treating areas of the human brain (such as the hippocampus) that are critical for memory and cognition and are known to be damaged as a result of TBI. We have previously shown that, in two rat models of TBI, NPLT improves neurocognitive outcomes, reduces neuroinflammation and neurodegeneration and normalizes neurogenesis. In this proposal, leveraging the combined expertise of a multidisciplinary team of bioengineers, physicians and neuroscientists who have collectively studied TBI for over 30 years, we will systematically develop this promising neuromodulation therapy by evaluating the onset and progression of neuropathology and associated cognitive dysfunctions in rats subjected to fluid percussion injury (FPI) and treated with NPLT in the acute or chronic phase of TBI. Moreover, we will conduct a systematic evaluation of how frequency (1 or 5 weekly applications) will affect NPLT efficacy to mitigate TBI outcomes. At the completion of the proposed studies, it is our expectation that we will have aided the development of a non-invasive treatment that, by reducing the onset of TBI-driven neuropathology and cognitive impairments, has the potential to reduce the global healthcare burden of TBI. The laser used for NPLT has received non- significant risk status by institutional review boards at UTMB for unrelated clinical applications thus supporting the feasibility of translating the use of NPLT to human patients once the work proposed in the present application will be completed.

抽象的 目前尚无针对数百万脑损伤（TBI）的有效治疗方法 每年在美国诊所看到的患者；因此，确定和发展有效 治疗仍然是公共卫生的紧迫，未满足的需求。我们的多学科团队有 开发了一种使用纳米脉冲的非侵入性经颅神经调节技术 光声激光疗法（NPLT）。我们的专有系统以光能水平运行 具有眼部安全和皮肤安全，易于交付，对该受试者的压力无压力。这项技术 结合近红外激光光，可减少脑部炎症并刺激神经元 电路 - 但不深入脑组织 - 和光声波，也 减少炎症并刺激神经回路 - 但它们更深地渗透到脑组织中， 允许治疗人脑的区域（例如海马） 记忆和认知，已知由于TBI而损坏。我们以前有 表明，在TBI的两种大鼠模型中，NPLT改善了神经认知结果，可减少 神经炎症和神经变性，并使神经发生归一化。在此提案中， 利用多学科的生物工程师，医生和 共同研究TBI超过30年的神经科学家，我们将系统地 通过评估和进展 大鼠的神经病理学和相关的认知功能障碍，受到液体打击乐的影响 损伤（FPI），并在TBI的急性或慢性期用NPLT处理。而且，我们会的 对频率（每周1或5个应用）如何影响NPLT进行系统评估 减轻TBI结果的功效。拟议的研究完成时，这是我们的 期望我们有助于发展非侵入性治疗的发展 减少TBI驱动的神经病理学和认知障碍的发作，具有潜力 减轻TBI的全球医疗保健负担。用于NPLT的激光已收到非 UTMB的机构审查委员会的显着风险状态无关临床 因此，应用支持将NPLT使用转化为人类患者的可行性 一旦本申请中提出的工作将完成。