Immune-Mediated Axonal Repair in the Injured Adult Mammalian CNS

Roman J. Giger, Ph.D.

University of Michigan School of Medicine

Funded in September, 2011: $200000 for 3 years


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Cellular imaging may reveal how immune inflammation can enhance neural regeneration in the CNS

Collaborating neuroscientists and immunologists will use cellular imaging in tissue from mice with damaged retinas to learn how retinal cells regenerate in response to activation of innate immune cells.  

Scientists continue to pursue avenues for regenerating nerves in the central nervous system (CNS) following their damage or destruction by spinal cord and brain injuries, infections, and diseases such as multiple sclerosis. Strategies involve efforts to support nerve cell survival, and repair and regeneration of CNS tissue.  It is well known that injury to the nervous system triggers rapid activation of the body’s first line of defense: its innate immune system. Upon injury or infection, this system initiates an inflammatory response. Depending upon the response’s extent and nature, it can be either protective or destructive for neurons. Optimal treatments, therefore, need to augment beneficial inflammatory functions while minimizing those that are detrimental. Animal studies have demonstrated how neural sprouting and regenerative growth can be limited during injury by substances released by “myelin,” the fatty sheath that covers the nerve cell’s axon and ordinarily helps it transmit the cell’s message to a neighbor. But one of the most exciting recent discoveries is that, under certain conditions, inflammation increases survival of retinal nerve cells (called ganglions) and regeneration of their severed axons. Understanding the cellular and molecular factors involved in inflammation, therefore, may lead to new ways to stimulate nerve growth.  

The investigators will use cellular imaging to systematically identify which immune system components directly participate in the observed regenerative growth response that occurs despite the presence of the growth-limiting factors released by myelin. They will view these events in autopsy tissue from a mouse model that the investigators developed. The model, through genetic and pharmaceological methods, enables them to identify the effects of specific immune cells and the proteins they produce. They will determine: 1) what types of immune system cells elicit neuroprotection and repair, 2) how those immune cells are attracted to the injured CNS, and 3) whether specific proteins can be identified that are sufficient to trigger nervous system regeneration.

Significance: The findings could lead to new approaches to stimulating selective innate immune responses that contribute to nervous system regeneration in people with devastating CNS injuries and diseases.