Strategies for the augmentation of grafted dopamine neuron survival.

摘要: The percentage of grafted embryonic DA neurons that survive transplantation is low, estimated at 5-20%. Significant agreement has emerged from the work research groups worldwide specific conditions associated with transplant procedure and post-transplantation interval render mesencephalic cells susceptible to apoptotic death. Detrimental triggers including hypoxia/ischemia, trophic factor withdrawal, oxidative stress appear exert most impact on neuron survival. Treatment strategies aim reduce or eliminate cell death be more successful than approaches target intracellular cascade. In particular, treatment suspensions isolated neurotrophic factors (GDNF, BDNF, NT 4/5) as well glial-derived factors, antioxidant therapies augmentation graft vasculature have demonstrated consistent survival promoting effects. Caspase inhibition, although initially quite promising, not been reliably increase Bcl-2 overexpression similarly yet prove beneficial, this may due biologically irrelevant levels bcl-2 present during critical immediate post-grafting interval. Future will a "cocktail" approach in which effective agents are combined maximize Refinements ex vivo transduction parameters allow for efficient sustained delivery cells. Once identified, optimal survival-enhancing primary should also benefit future utilizing alternatively derived neurons.