The Silver lab is dedicated to the functional repair of the chronically injured spinal cord. We have developed a number of animal models to mimic both complete inury (transection) as well as severe contusive injury (with a small amount of spared tissue), During my presentation I will update those at W2W on our chronic (2 months) contusive injury model and our efforts to build a bridge across the lesion. Our strategy here combines surgical scar removal + chondroitinase + fibroblast growth factor to maximize the capacity of peripheral nerve autografts to provide a regeneration bridge across the chronic lesion. We are excited to report that we are now describing for the first time a robust regeneration of certain (but not all) supraspinal axon tracts with some recovery of bladder function. We are now in the process of further maximizing this strategy by further combining a novel regenerative peptide. I will also discuss a pilot study of 6 months chronic contusive animals injected only with chondroitinase and the regenerative peptide (no bridge building). I am excited to report that half of the animals have nicely improved daily urinary output with also remarkably improved physiology of bladder and sphincter coordination. Some of these animals also recovered the ability to grid walk. I will discuss our further plans to carry on with these experiments. Finally, I will briefly mention our collaborative chronic work on the respiratory system after hemisection lesion at C2 (up to 1.5 years after injury) in collaboration with the Warren Alilain lab. We have documented remarkable return of breathing using chondroitinase + intermittent hypoxia. We also understand now why too much intermittent hypoxia can cause problems in some animals and by understanding the basic biology of how the serotonergic system is influenced by these treatments we have learned how to maximize the return of proper rather than chaotic function. Now that we are finally beginning to show promising functional recovery at chronic time points after SCI we should be optimistic that our successes in animal models can lead to translation in spinal cord injured people.
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