Using Three-Dimensional In Vitro Neural Spheroid Models to Study Ischemic Stroke and Traumatic Brain Injury
Cox, Victor F. (creator)
Hoffman-Kim, Diane (Advisor)
Franck, Christian (Reader)
Achilli, Toni-Marie (Reader)
Brown University. Department of Molecular Pharmacology, Physiology and Biotechnology (sponsor)
Traumatic brain injury (TBI) is a major cause of injury and disability, and 30 percent of all injury related deaths in United States can be attributed to TBI (Taylor et al., 2007). TBI is caused by a bump, blow or jolt to the head that disrupts normal function of brain and ranges from mild to severe (Centers for Disease Control and Prevention [CDC], 2017). The effects of TBI can include impaired thinking, memory, movement, sensation, or emotional function (CDC, 2017). Common causes of traumatic brain injury are falls, motor vehicle accidents, and contact sports (CDC, 2017). Progress for developing therapies to treat TBI is slow, especially since the distribution of the forces resulting from an insult and the cellular molecular mechanisms that are involved in injury are not well characterized (Shoichet et al., 2008). A clinically relevant model to study TBI is necessary to characterize the cellular molecular pathophysiology of TBI and to perform translational studies. 3D cortical spheroids represent features found in vivo and have shown success in characterizing some of the effects of ischemic stroke. Gel compression platforms for neurons have proven successful in characterizing the effects of neuronal injury (Bar-Kochba et al., 2016). This study explores polyacrylamide and collagen type 1 as candidate materials for fabricating spheroid containing hydrogels for uniaxial compression as a model for TBI. 3D cortical micro-tissues were embedded into collagen type I gels and exposed to uniaxial compression by a 3D neuronal compression device. Embedding spheroids in collagen for compression allows us to study the effects of impact in a population of cells that possess several of the characteristics expected in vivo.
Cox, Victor F.,
"Using Three-Dimensional In Vitro Neural Spheroid Models to Study Ischemic Stroke and Traumatic Brain Injury"
Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations.
Brown Digital Repository. Brown University Library.