Approximately 5,596,000 people in the United States live with some form of paralysis; among these, 1,275,000 are paralyzed as the result of a spinal cord injury (SCI). The lack of treatment results in a constantly growing population. Each year, SCI cost to the health care system is roughly 40.5 billion. SCI triggers profound changes in the behavior of glial cells, which limit secondary injury and influence regeneration. However, the distinct roles of different glial cell types in the recovery from SCI are not well understood. NG2+ glial cells, a class of glial progenitors that generate oligodendrocytes in the developing and adul CNS, are rapidly mobilized following SCI; they increase their proliferation and migrate to the site of injury. The consequences of this recruitment of NG2+ cells are unknown. Although the behavior of these cells has been viewed primarily in the context of oligodendrocyte regeneration, recent studies suggest that they may play additional roles in the pathophysiology of SCI. In this exploratory research grant (R21) we propose to examine the fate of these highly dynamic cells and evaluate their contribution to functional recovery using in vivo genetic lineage tracing, in vivo two photon imaging, and in vivo selective cell ablation in a clinically relevant model of contusion-induced SCI. The knowledge gained from these studies may reveal new therapeutic strategies based on manipulation of this endogenous pool of progenitors as well as targeted manipulation of NG2+ cells (also termed oligodendrocyte precursor cells (OPCs) engineered for transplantation therapy.
Spinal cord injury, a devastating condition that affects approximately 1.2 million people in the United States, induces a massive increase in the proliferation of a population of glial cells termed NG2+ cells. In addition to serving as progenitos for oligodendrocytes, recent discoveries suggest that these cells play important roles in the evolution of the injury and therefore may play a critical role in functional recovery. Manipulation of these endogenous cells as well as their transplantation is of great interest as a possible treatment for paralysis; therefore, we have design several experiments using state-of-the art technologies to study this specific population of cells in a mouse model of contusive spinal cord injury.
| Larson, Valerie A; Zhang, Ye; Bergles, Dwight E (2016) Electrophysiological properties of NG2(+) cells: Matching physiological studies with gene expression profiles. Brain Res 1638:138-160 |
