Cellular and molecular responses in human spinal cord injury

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There is considerable evidence from animal studies that glial, endothelial and mesenchymal responses represent a prominent component of central nervous system (CNS) injury. However, little is known about the cellular and molecular responses that occur following spinal cord injury (SCI), and not all of the responses of cells have been obtained from in vitro studies, and the relevance of these findings to in vivo conditions, particularly in humans, is not known. The goal of this project is to clarify the role of glia (astrocytes, microglia, oligodendroglial, ependymal cells), Schwann cells and mesenchymal cells (endothelial cells, neutrophils, macrophages, meningeal cells, fibroblasts) in trauma-induced injury to the human spinal cord. A major focus of this study will be the identification of "beneficial" and "detrimental" factors, i.e., their cellular localization and temporal profile. The changes will be correlated with clinical course and therapy. The availability of an extensive bank of human cases of SCI in the Miami Project to Cure Paralysis will facilitate the acquisition of these critical data that can serve as the basis for future animal studies on potential strategies to alter the cellular and molecular environment following injury, to rescue damaged cells, and to promote axonal growth and regeneration in humans after SCI. Our general hypothesis, based on available data from in vitro studies, and animal models of trauma-induced injury to the nervous system, is that human SCI induces a variety of glial- and mesenchymal-derived homeostatic. inflammatory, neurotrophic and neuroinhibitory factors which may be related to the duration or type of injury, and may determine clinical outcome and response to therapy.