성숙 Gerbil의 일과성 전뇌 허혈모델에서 해마의 지연성 신경세포 손상에 대한 Calcitriol의 영향

Abstract

Background : It is well documented that calcium ions perform a major role in neuronal degeneration in cerebrovascular disease and the other degenerative diseases, and that 1,25-dihydroxyvitamin D3 (D3) has the dose-dependent protective effects. This study was performed to examine the effects of different D3 dosages against delayed neuronal damage of the hippocampus. Methods : Mature mongolian gerbils were injected with either 0.8 μg/kg/day (group 2) for 5 days or 1.0 μg/kg/day for 8 days (group 3) prior to the 10 min ligation of the bilateral common carotid arteries. Immunohistochemical expression for the glial cell linederived neurotrophic factor (GDNF), the basic fibroblast growth factor (bFGF) and the plateletderived neurotrophic factor (PDNF) was observed in the D3-injected (0.8 μ g/kg/day for 5 days) group. Results : Group 2 showed a highly significant attenuation of delayed neuronal damage in the lateral CA1 region at 7 days after reperfusion. Group 3 showed unilateral or bilateral hemispheric infarcts 24 h after the onset of reperfusion. The D3-injected group showed a markedly increased bFGF expression level. Conclusion : The dose-dependent effect of D3 suggests the importance of determining the appropriate D3 dose for clinical applications. Although the mechanism(s) of neuroprotection by D3 remains unclear, D3 may facilitate a reduction in ischemia-induced oxidative stress via the activation of the neurotrophic factors, including bFGF and GDNF.