Manipulating Immune Response to Boost Nerve Regeneration

One of the reasons that nerves regenerate poorly has to do with the way in which the immune system responds to traumatic injury. In essence its behavior tends towards the formation of scar tissue that blocks nerve regrowth rather than allowing for regeneration. With greater understanding of the underlying mechanisms, researchers can try to change this state of affairs:

By altering activity of the macrophage cells that respond to injuries, researchers dramatically increased the rate at which nerve processes regrew. Influencing the macrophages immediately after injury may affect the whole cascade of biochemical events that occurs after nerve damage, potentially eliminating the need to directly stimulate the growth of axons using nerve growth factors.

Macrophages can exist in several different phenotypes depending on the signals they receive. Among the macrophage phenotypes are two classes - M2a and M2c - that encourage healing. [The] research team used an interleukin 4 (IL-4) cytokine to convert macrophages within the animal model to the "pro-healing" phenotypes. They placed a gel that released IL-4 into hollow polymeric nerve guides that connected the ends of severed animal sciatic nerves that had to grow across a 15 millimeter gap to regenerate. The IL-4 remained in the nerve guides for 24 hours or less, and had no direct influence on the growth of nerve tissue in this short period of time.

Three weeks after the injury, the nerve guides that released IL-4 were almost completely filled with re-grown axons. The treated nerve guides had approximately 20 times more nerve regeneration than the control channels, which had no IL-4-treated macrophages. Research is now underway to develop the technique for determining how soon after injury the macrophages should be treated, and what concentration of IL-4 would be most effective.

Link: http://www.eurekalert.org/pub_releases/2012-10/giot-ssi100212.php

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