Successes in chronic injury

If you want to get injured axons to regenerate across the injury site it is pretty clear you need to adopt a combinatorial approach. Simply placing Schwann cells into the injury, for example, results in regeneration of axons into the graft but they refuse to come out again back into the cord. Even introducing “axon candy” – neurotrophins – to entice regenerating axons to leave the graft doesn’t always work (see earlier post).

The Tuszynski lab (UCSD, La Jolla, CA) presented findings on a 3-pronged combinatorial approach employing neurotrophins to attract axons, cellular grafts to act as tissue bridges across the injury and techniques (a peripheral nerve pre-conditioning injury, if you want to know) to stimulate the neurons to regenerate (SfN2009 Program# 365.6). And they did this is a 15 month old chronic injury rather than acute. They showed that you could achieve regeneration of sensory neurons – those neurons relaying information from the body back towards the brain – beyond the graft site even at these chronic time points, albeit to a lesser degree than if intervention were carried out acutely. Nevertheless, it did show that injured neurons could respond to treatment well after an injury.

Today (SfN2009 Program# 542.1), the group presented their findings on the capacity of descending neuronal fibres – those conveying signals from the brain to the body important for motor control – to respond to combinatorial therapy broadly similar to that described above. A couple of important differences are worth mentioning; (i) you can’t perform a pre-conditioning injury to the descending pathways so administration of a small molecule called cAMP is used as a pharmacological equivalent and; (ii) some of the animals where additionally treated with chondroitinase (see earlier post), the reason being chondroitinase should break down scar tissue where you want the regenerating axons to exit the cellular graft. They found significant improvements in function in the “full” combination group which included the chondroitinase even in the chronic injury.