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: 10512316
• 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/10512316
• 关键词: Acute; Affect; Area; Biomedical Engineering; Brain; Brain Injuries; Brain Pathology; Chronic; Chronic Phase; Clinic; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Development; Diagnostic; Encephalitis; Evaluation; Eye; Frequencies; Goals; Healthcare; Hemoglobin; Hippocampus (Brain); Hour; Human; Impaired cognition; Inflammation; Institutional Review Boards; Lasers; Life; Light; Low-Level Laser Therapy; Medical; Memory; Modeling; Monitor; Nerve Degeneration; Neurocognitive; Neurologic; Operating System; Optics; Outcome; Pathology; Patients; Phase; Physicians; Physiologic pulse; Pre-Clinical Model; Public Health; Publishing; Rattus; Research; Risk; Skin; Stress; Structure; Suggestion; TBI Patients; TBI treatment; Techniques; Technology; Translating; Traumatic Brain Injury; Travel; Treatment Efficacy; Work; base; brain tissue; chromophore; clinical application; cognitive change; disability; effective therapy; efficacy evaluation; expectation; fluid percussion injury; improved; multidisciplinary; nano; nanosecond; nervous system disorder; neural circuit; neurogenesis; neuroinflammation; neuronal circuitry; neuropathology; 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，数以百万计的创伤性脑损伤（TBI）患者还没有有效的治疗方法 每年在美国诊所就诊的患者；因此，确定并制定有效的 治疗仍然是公共卫生领域迫切且未得到满足的需求。我们的多学科团队拥有 开发了一种使用纳米脉冲的非侵入性经颅神经调节技术 光声激光治疗（NPLT）。我们的专有系统在光能水平下运行 对眼睛和皮肤安全、易于交付且对受试者无压力。这项技术 结合近红外激光，可减少大脑炎症并刺激神经元 电路 - 但不会深入渗透到脑组织 - 和光声波，这也 减少炎症并刺激神经回路 - 但它们更深入地渗透到脑组织中， 允许治疗对人类大脑至关重要的区域（例如海马体） 已知 TBI 会导致记忆和认知受损。我们之前有过 研究表明，在两种 TBI 大鼠模型中，NPLT 可以改善神经认知结果，减少 神经炎症和神经变性并使神经发生正常化。在这个提案中， 利用生物工程师、医生和多学科团队的综合专业知识 共同研究 TBI 30 多年的神经科学家，我们将系统地 通过评估神经调节的发生和进展来开发这种有前途的神经调节疗法 流体冲击大鼠的神经病理学和相关认知功能障碍 损伤 (FPI) 并在 TBI 的急性或慢性阶段使用 NPLT 进行治疗。此外，我们将 对频率（每周 1 或 5 次申请）如何影响 NPLT 进行系统评估 减轻 TBI 后果的功效。在完成拟议的研究后，我们 期望我们能够帮助开发一种非侵入性治疗方法，通过 减少 TBI 驱动的神经病理学和认知障碍的发生，具有潜力 减轻 TBI 造成的全球医疗保健负担。用于 NPLT 的激光器已收到非 UTMB 机构审查委员会对不相关临床的重大风险状态 从而支持将 NPLT 应用于人类患者的可行性 一旦本申请中提议的工作完成。