Traumatic brain injury (TBI) impacts 2.5 million people in the U.S. annually. Most people will sustain mild TBI (mTBI). with approximately 13% experiencing chronic cognitive symptoms impacting quality of life. Individuals with mTBI report experiencing sub-clinical deficits in language that include difficulty with starting. maintaining. and following conversations. However. these symptoms are mostly self-reported and elusive using existing clinical tools. Language comprehension demands the efficient construction of a coherent message from a rapid stream of input.

Traumatic brain injury (TBI) and many other brain diseases/injuries exhibit sex differences in prevalence. onset. and outcomes. Some of these differences are attributed to the fact that the human brain is sexually dimorphic and there are certain regional and structural differences that exist between male and female brains. However. the effect of these sex variations in biomechanical responses of brain have not been elucidated. The paucity of sex-specific knowledge in brain biomechanics and TBI fields is mainly due to the fact that. these fields have predominantly focused on males.

In light of the currently extant Covid pandemic. the impact of understanding upper airway health and being prepared for the rapid development of novel therapeutics has been reinforced. While preclinical animal models have long been the gold standard for the testing and development of novel therapeutics. they are expensive and time consuming. The availability of validated. reproducible and scalable in vitro diagnostics that reproduce relevant physiology and function as test-benches for the rapid testing and development of personalized medicine therapeutics is thus invaluable.

In the U.S. alone, 2.8 million people sustain a traumatic brain injury (TBI) each year and seek medical care.1,2 However, there are no FDA approved therapies for effective treatment of TBI (or concussion) patients. Current medications are limited to only reducing secondary damage to the brain following TBI, such as using diuretics to reduce the pressure inside the brain by increasing urine output.

Major Goal: The goal of this grant application is to produce clinical grade human neural stem cells from embryonic stem cells and to demonstrate their long-term safety and efficacy in a rodent and a nonhuman primate model (marmoset) of acute focal traumatic brain injury (TBI).