The fate of proliferating cells in the injured adult spinal cord

Endogenous cell proliferation and gliogenesis have been extensively documented in spinal cord injury, particularly in terms of proliferating oligodendrocyte progenitor cells. Despite the characterization of different proliferating cell types in the intact and injured spinal cord, the exact sources of new glial cells have remained elusive. Most studies on cell fate within the spinal cord have focused on following the progeny of one specific population of dividing cells, thus making it difficult to understand the relative contributions of each mitotic cell population to the formation of new glia after spinal cord injury. A recent study from the Frisen laboratory is the first to quantitatively and qualitatively characterize the response of ependymal cells, oligodendrocyte progenitors, and astrocytes in parallel by using transgenic reporter mice corresponding to each cell type. The investigators characterize the distribution and phenotype of progeny, along with the quantitative contributions of each progenitor type to newly formed cells. Their findings provide valuable insight into the endogenous cell replacement response to spinal cord injury, thus paving the way for advances in modulating specific populations of progenitor cells with the goal of promoting structural and functional recovery after spinal cord injury

The Role of Acute Intraspinal Hemorrhage After Spinal Cord Injury

Poster Division: Biological Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Spinal cord (SCI) injury initiates a cascade of destructive and reparative processes, an understanding of which may help in designing strategies for minimizing tissue loss and enhancing endogenous repair. Vascular disruption and hemorrhage is a prominent characteristic of the acute lesion environment, and is central to many of the secondary pathological consequences of SCI, most notably lesion formation. However its role, if any, in reparative processes is not known. An important endogenous repair mechanism after SCI is the proliferation of NG2+ cells and their maturation into new oligodendrocytes. We created a rat model of collagenase-induced intraspinal hemorrhage (ISH), and investigated the spatial-temporal dynamics of lesion formation, astrogliosis, microglia/macrophage reactivity, NG2 cell proliferation, and mature oligodendrocyte numbers after injury. Lesion pathology was similar to a contusion injury; however, lesion size, shape and spread were different between ISH and contusion. The astrocyte and macrophage responses of ISH were also similar to that of a contusion. In addition, we determined that hemorrhage alone is sufficient to initiate NG2 cell proliferation as early as 1dpi and continuing up to a week. Furthermore, oligodendrocyte numbers decreased by hemorrhagic injury are rapidly restored to normal levels by 7dpi. We have established that acute intraspinal hemorrhage following a SCI is not only the central initiating force for secondary injury cascades, but that it also plays a role in stimulating acute NG2 proliferation following injury.A one-year embargo was granted for this item

Oligodendrocyte Fate after Spinal Cord Injury

Oligodendrocytes (OLs) are particularly susceptible to the toxicity of the acute lesion environment after spinal cord injury (SCI). They undergo both necrosis and apoptosis acutely, with apoptosis continuing at chronic time points. Loss of OLs causes demyelination and impairs axon function and survival. In parallel, a rapid and protracted OL progenitor cell proliferative response occurs, especially at the lesion borders. Proliferating and migrating OL progenitor cells differentiate into myelinating OLs, which remyelinate demyelinated axons starting at 2 weeks post-injury. The progression of OL lineage cells into mature OLs in the adult after injury recapitulates development to some degree, owing to the plethora of factors within the injury milieu. Although robust, this endogenous oligogenic response is insufficient against OL loss and demyelination. First, in this review we analyze the major spatial–temporal mechanisms of OL loss, replacement, and myelination, with the purpose of highlighting potential areas of intervention after SCI. We then discuss studies on OL protection and replacement. Growth factors have been used both to boost the endogenous progenitor response, and in conjunction with progenitor transplantation to facilitate survival and OL fate. Considerable progress has been made with embryonic stem cell-derived cells and adult neural progenitor cells. For therapies targeting oligogenesis to be successful, endogenous responses and the effects of the acute and chronic lesion environment on OL lineage cells must be understood in detail, and in relation, the optimal therapeutic window for such strategies must also be determined