|Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2004 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2003 : ¥2,200,000 (Direct Cost : ¥2,200,000)
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.