The fetal brain is known to be survival from severe hypoxia during delivery, although its physiological mechanism remains unclear. We studied the roles of Bcl-2 (caspase-3 suppressor) and Bax (caspase-3 activator) in the hypoxia-induced activation of caspase-3 in the superior colliculus (SC) in a fetal rat, which was still connected with the anesthetized dam (urethane, 1.2-1.4 g/kg, i.p.) by the umbilical cord. Caspase-3 activity was measured with fluorescent caspase-3 substrate using an optical imaging system. Hypoxia was induced by occlusion of the umbilical cord for 5 min, and repeated every 1 hr up to 3 hrs after the initial occlusion. We observed a transient rise in caspase-3 activity following the initial occlusion. After reperfusion of the umbilical cord, caspase-3 activity gradually increased and afterward returned almost to the control level. Caspase-3 activation was more robust and long-lasting following the 3rd and 4th occlusion compared to the initial occlusion. Apoptosis of fetal SC cells was significantly increased after the umbilical occlusion. Application of Bcl-2 inhibitors unexpectedly suppressed the hypoxia-induced caspase-3 activation, while Bax inhibitors caused no effect. Further experiments are needed to clarify the unexpected result on Bcl-2 in association with apoptosis. [J Physiol Sci. 2007;57 Suppl:S115]
