The processes of degeneration and regeneration are intertwined in both their impact on, and potential benefits to, the goal of improved functional outcome after CNS injury. Research towards potential interventions for spinal cord and other CNS injuries must therefore be aimed at both of these targets. Hence, my laboratory focuses on two principal goals.

1 – Investigating the role of inflammatory mechanisms in degeneration and regeneration in the injured central nervous system (CNS), in particular the spinal cord, and the interactions of inflammatory mechanisms with these critical processes.
The complement system is a principal effector for multiple inflammatory mechanisms, from phagocytosis to lytic cell loss, however, little attention has been paid to investigating the complement system after spinal cord injury.

In recent studies, we have shown that all pathways of complement are activated after spinal cord injury, and defined the cellular localization and timecourse of immunoreactivity for complement in mice and rats. Additional studies of the effects of complement inhibitors on histological and functional outcome after contusion spinal cord injury suggest that this line of research may provide insight into potential therapeutics.

Ongoing and planned studies include:

  • Investigating the cellular source of complement in the spinal cord.
  • Using transgenic mice lacking complement components to clarify the role and contribution of complement to CNS injury.
  • Investigating the interaction between enriched environment/physical exercise, immune function, and outcome after spinal cord/CNS injury.

These studies are important to understand the interactions of the immune and central nervous systems, and to determine whether complement inhibitors or therapeutics could be of benefit after human spinal cord injury.

2 – Investigating the ability to use human stem cells to ameliorate the functional deficits associated with spinal cord injuries and promote recovery. Stem cells are a strong focus of current interest for the potential treatment of many types of CNS disease and injury. While the majority of stem cell lines that have currently been isolated are uncommitted and must be cultured in the presence of molecules that influence their cell fate prior to transplantation, the cells our laboratory works with are neural-committed.

These human central nervous system stem cells (hCNS-SC) have been shown to migrate extensively after grafting into the uninjured fetal and adult brain, and to differentiate into functional neurons, as well as oligodendrocytes, and astrocytes.

These projects make use of NOD-Scid mice, which immunodeficient and therefore exhibit a much attenuated rejection of xenografted (human to mouse) cells. Current studies show that NOD-Scid mice respond to spinal cord contusion injuries similar to background strain, and that transplantation of hCNS-SC into contusion-injured Nod-Scid mice leads to improvements in functional recovery.

Ongoing and planned studies include:

  • Investigating and comparing NOD-Scid and NOD mice for spinal cord injury response characteristics.
  • Investigating the engraftment, survival, and differentation of hCNS-SC neurospheres in spinal cord injured NOD-Scid mice, the ablility of these cells to promote recovery from injury, and the mechanisms by which this recovery takes place.