Effects of Calcitriol on Delayed Neuronal Damage of Hippocampus in Transient Global Ischemia Model of Mature Gerbil

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 microgram/kg/day (group 2) for 5 days or 1.0 microgram/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 line-derived neurotrophic factor (GDNF), the basic fibroblast growth factor (bFGF) and the platelet-derived neurotrophic factor (PDNF) was observed in the D3-injected (0.8 microgram/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.