Research points to a multiplicity of possible interventions to promote recovery from a spinal injury. Some would be delivered immediately following the injury; others are less time-specific and involve rebuilding and reconnecting the injured cord. Clearly, both approaches are important: Limiting degeneration will enhance the probability of greater recovery, while stimulating regeneration will build upon the remaining system to restore lost connectivity and perhaps to prevent further degeneration.
The following are some of the intervention strategies supported by funding from the Christopher & Dana Reeve Foundation. This is not a comprehensive list of all possible interventions.
Treatments Immediately Following an Accident
Limiting initial degeneration
Recent research has shown that there are at least three different mechanisms of cell death at play in neuronal and oligodendrocyte loss after injury: Necrosis, excitotoxicity, and apoptosis.
Soon after injury, the spinal cord swells and proteins from the immune system invade the injured zone. This swelling and inflammation may foster secondary damage to the cord after the initial injury. So it is important to treat the inflammatory response as quickly as possible. Labs pursuing this approach include the Schwab Lab.
Stimulating axonal growth
Nerve fertilizers called neurotrophins can promote cell survival by blocking apoptosis and stimulate axonal growth. Each neurotrophin has a very specific target cell function. Some selectively prevent oligodendrocyte cell death, others promote axon regrowth or neuron survival, and still others serve multiple functions. Labs pursuing this approach include the Black Lab and the Parada Lab.
Promoting new growth through substrate or guidance molecules
Substrate and guidance molecules may improve targeting once axons have been encouraged to regenerate past the lesion site. These proteins act as roadmaps, steering axons to their correct targets. This is a critical function because even if axons do survive, they must reconnect with the correct targets. Labs pursuing this approach include the Black Lab, the Mendell Lab, and the Parada Lab.
Blocking molecules that inhibit regeneration
There are molecules within the brain and spinal cord that prevent neurons from dividing and axons from growing. Overcoming inhibition can stimulate axonal regrowth and regeneration and is likely to be an important component of regenerative therapies. The Schwab Lab is pursuing this approach.
Supplying new cells to replace lost ones
Stem cells, which are isolated from the CNS and can divide to form new cells, may replace lost neurons and gila. These stem cells must be harvested, treated to encourage growth, and then injected into the injured cord. Labs pursuing such an approach include the Bunge Lab and the Gage Lab.
Building bridges to span the lesion cavity
Bridges may be needed to reconnect the severed sections of the injured spinal cord. Scientists must determine how best to build these bridges and what molecules to use to encourage new growth and enhance survival of new connections. The Bunge Lab is pursuing this approach.