Following injury to the central nervous system, axons are unable to spontaneously regenerate. Reasons for the lack of regeneration include the absence of a growth promoting substrate within the lesion site, an increase of inhibitory signals surrounding the lesion site, and a failure to initiate an intrinsic growth-promoting program within the injured cell body. I am interested in utilizing combinatorial strategies to promote axon regeneration and/or sprouting that results in functional recovery following spinal cord injury (SCI).
Previous and ongoing work from our lab shows that certain axons, such as sensory dorsal column axons, can regenerate and bridge a SCI lesion site in response to growth factors. Corticospinal (CS) axons, however, are unable to respond to such cues. This may be due in part to atrophy and/or cell death of CS neurons following SCI. Interestingly, this atrophy and/or cell death can be prevented with growth factors delivered to the injured spinal cord despite the fact that CS axons do not regenerate in response to these same growth factors. This suggests that CS neuronal cell bodies are able to respond to growth cues and may be able to initiate a growth-promoting program. As yet, the appropriate cue and/or substrate to promote CS axonal regeneration has not been ascertained.
My focus is on combining therapeutic strategies. This includes: utilizing pharmacological agents to enhance growth-promoting programs, providing cellular transplants as a favorable substrate for regeneration through sites of SCI and making use of gene therapy vectors that provide the appropriate cues for guiding regenerating axons to their correct targets.
John Brock, PhD
Assistant Project Scientist