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.
