Modern medicine has few treatment options for brain injuries. In many diseases, the most effective therapies are based on detailed knowledge of pathophysiology, but relatively little is known about how the central nervous system (CNS) responds to environmental changes induced by trauma or stroke. This lack of knowledge is central to why treatments for CNS injuries have lagged behind those available for other organ systems. The goal of my research is to understand how a seemingly mature nervous system responds to environmental challenges such as injury, and how neural stem cells participate in this process. Throughout development, neural stem cells give rise to differentiated neurons, astrocytes, and oligodendrocytes which together modulate perception, memory, and behavior in the adult nervous system. To understand how neural stem cells contribute to brain remodeling after injury, we focus on the subventricular zone (SVZ) of the lateral ventricles in the postnatal/adult brain, an area containing self- renewing stem cells that generate immature neurons throughout life. Current studies of SVZ neurogenesis and stem cell behavior after brain injury involve either fixed tissues from sacrificed animals, or dissociated cells cultured in vitro in the presence of serum and growth factors. Inconsistent findings from established laboratories have prevented neural stem cell research from rapidly moving beyond phenomenology into fulfilling their potential as endogenous therapeutic agents, and point to a clear need for better assays and tools. My laboratory has generated a novel method to both indentify SVZ cells after brain injury and to image their behavior in intact brain tissue. The goal of this proposal is to use these novel techniques, in combination with innovations in optical engineering and chemical screening to advance our understanding of how tissue stem cells deal with environmental change, and to identify new therapeutic strategies for brain injuries.
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