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

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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.