Neuroprotective effect of nerve growth factor, GDNF, on spinal ischemia

我们进行了一项研究，以阐明神经生长因子，胶质细胞系来源的神经营养因子（GDNF）对大鼠脊髓缺血和再灌注模型的神经保护作用。我们发现，短暂性脊髓缺血后，GDNF在2小时短暂增加，24小时恢复到基线值，然后在72小时再次增加。缺血2小时后GDNF的增加可能来源于α运动神经元，72小时后GDNF的再次增加可能来源于星形胶质细胞。这表明GDNF可能在缺血性损伤的改善中发挥作用。我们推测GDNF可能具有生理上的抗缺血作用，或者可能在缺血后时期缺血性神经损伤的改善中发挥作用。（Tokumine J， journal of Neurochir[增刊]2003）。为了进行比较，我们还检测了其他神经生长因子，即脑源性神经营养因子（BDNF）和神经营养因子3（NT-3）的缺血后动态。BDNF在缺血后逐渐增加，维持高组织水平长达72小时。NT-3在缺血后无明显变化。（Tokumine J, J Neurosci Res 2003）。另一方面，与其他神经生长因子相比，GDNF表现出不同的动态。因此，我们假设GDNF在抗缺血的神经保护中发挥特定的生理作用，特别是在缺血后早期。下一步，我们研究了一种名为FK506（他克莫司）的药物的作用，它可能会提高GDNF水平，因为它在大鼠短暂性缺血模型中具有潜在的神经保护作用。缺血后立即给予FK506可显著改善缺血后24小时和48小时的神经预后（描述相同内容的文件正在准备中）。综上所述，GDNF是一种内源性生物活性物质，在缺血后可能具有神经保护作用。

We conducted a study to clarify the neuroprotective effects of the nerve growth factor, Glial cell line-derived neurotrophic factor(GDNF), on a rat spinal ischemic and re-perfusion model. We found that after transient spinal ischemia, GDNF increased transiently at 2 hours, returning to baseline values at 24 hours, and then increased once again at 72 hours. The increase in GDNF 2 hours after ischemia was probably due to GDNF derived from α motor neurons, the re-increase at 72 hours probably being derived from astrocytes. This suggests that GDNF potentially plays a role in the amelioration of ischemic damage. We postulated that GDNF either has a physiologically anti-ischemic effect, or that it might play a role in the amelioration of ischemic neurological damage in the post-ischemic period. (Tokumine J, Acta Neurochir [Suppl] 2003).For the purpose of comparison, we also examined the post-ischemic dynamics of other nerve growth factors, namely Brain-derived neurotrophic factor(BDNF) and Neurotrophin 3(NT-3). BDNF was found to gradually increase after ischemia, maintaining high tissue levels for up to 72 hours. NT-3, however, showed no change in the post- ischemic period. (Tokumine J, J Neurosci Res 2003). GDNF on the other hand, showed different dynamics in comparison with these other nerve growth factors. Therefore, we hypothesized that GDNF plays a specific physiological role in neuroprotection against ischemia, especially in the early post-ischemic phase.As a next step, we studied the effect of a drug called FK506(tacrolimus), which may elevate GDNF levels, for its potential neuroprotective potency in the rat transient ischemia model. Administration of FK506 just after ischemia resulted in a significantly improved neurological outcome at 24 hours and 48 hours after ischemia (the document describing the same is being prepared for presentation).In conclusion, GDNF is an endogenous bioactive substance having probable neuroprotective effects post-ischemia.