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Abstract
Brain disorders are as diverse as they are devastating with few effective treatment options. The current challenge in diagnosing and treating neurological disorders is a lack in understanding regarding root causes leading to observed behavioral and biochemical alterations. Clinical and animal models provide substantial information but these models are complex with systemic and multicellular response to injury making mechanistic study difficult and vague. Fortunately, advances in our knowledge of in vitro cell culture and biomaterials have inspired the engineering of novel platforms for the study of physiologically relevant conditions leading to brain disorder. This work outlines the development of three in vitro models for the study of molecular mechanism leading to brain disorder due to aberration in static tissue mechanical properties, traumatic mechanical injury and methamphetamine abuse.
These in vitro platforms utilize astrocytes which are the most abundant glial cell in the brain. These cells perform a number of important roles for proper brain function including blood brain barrier manipulation, neurotransmitter recycling, and tissue repair. Due to the overall abundance of cells and diversity of cellular function, astrocytes have been identified as a potential target for therapeutic manipulation to improve disease and injury prognosis. Of particular interest is the astrogliotic phenotype which is observed in numerous disease and injury pathologies to have both detrimental and healing characteristics. This work establishes and utilizes in vitro platforms for the understanding of cellular processes induced by static mechanical properties, dynamic mechanical damage and methamphetamine for greater understanding of astrocytes’ role in disorder progression and potential for therapeutic manipulation.
