SCI is a relatively frequent event; estimates suggest that 12,500 new cases of SCI occur every year in the US alone. In the US, approximately 276,000 persons live with SCI, which has a huge impact on their lives and families, and has tremendous socioeconomic and medical costs. The main causes for SCI are motor vehicle accidents (38%), falls (30%), acts of violence (14%) and sports injuries (9%) (National SCI Database).
The type and degree of disability that is caused by SCI is determined by the location and extent of the injury. Spinal cord tissue is damaged in the injury process and this damage is occurring in two steps. The initial damage, the primary injury, is caused by the mechanical trauma to the spinal cord during the accident.
This is followed by the secondary injury, which is caused by a number of events including hemorrhage and inflammation. While acute inflammation is observed in all tissues as a response to injury and is an important prerequisite for the healing process, prolonged and unresolved inflammation, as it is present after SCI, strongly contribute to the tissue damage. Immune cells in the tissue produce factors that maintain and stimulate the inflammatory response and produce factors that contribute to tissue damage.
CD11b+ macrophages / microglia accumulate after SCI
Red blood cells (RBCs), which are present in the spinal cord tissue due to the hemorrhage, are taken up by phagocytic cells like macrophages. This can result in increased production of pro-inflammatory cytokines and chemokines, factors that activate immune cells. Previous experiments have shown the relevance of some of these factors after SCI. For example, the absence of one of these cytokines, TNF, leads to a better recovery in mice after SCI and reduces inflammatory activation of cells at the injury site. However, these extent of these results suggests that other factors also contribute to the tissue damage.
We are now attempting to investigate further mechanisms contributing to the secondary tissue damage, including other cytokines and chemokines which may play a role after SCI. We aim to modulate these and investigate the effect on recovery after SCI.
Ultimately, our goal is a translational treatment approach to reduce secondary damage after injury and to improve the outcome and quality of life after SCI.
In summary, the broad goal of my research is to investigate and modulate the inflammatory tissue response after spinal cord injury (SCI) with the aim to reduce the secondary damage and thereby to improve the functional outcome after SCI.