Biofidelic Three-Dimensional Brain Surrogate Models of mTBI-Induced Alzheimer's Disease Pathology
Technical Report,15 Sep 2015,14 Sep 2019
Leland Stanford Junior University Stanford
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The vast complexity of the brain, with its hundred billion neurons and supporting cells as well as hundreds of trillion connections, poses a tremendous roadblock for scientists to understand the working of the brain on molecular, cellular, or circuit levels. Defining the genetic programs that drive neural function, the cell-type specific contributions to neural circuit working, the mapping of connectivity patterns within and between individual networks, and elucidating the mechanisms of disease present only a few examples of the challenges. Novel approaches and technologies are needed to complement and advance the state-of-the art in vivo, ex vivo, and in vitro approaches to study brain physiology and pathology. Here, we are proposing to bioengineering a validated in vitro 3-dimensional 3D brain surrogate mTBIAD model built of primary mouse neurons. Our research proposal builds upon the shock wave model of mTBI, which postulates that mTBI iscaused by the primary shock wave from a blast that penetrates through the skull and traverses the brain. We will use this to elucidate the mechanisms leading to open field blast explosives induced mTBI and its relationship to Alzheimers disease, including discovery by proteomic, genomic, and in vivo analysis of mice of new mTBIAD biomarkers and disease pathways.
- Medicine and Medical Research
- Anatomy and Physiology