We investigated the effect of
vinconate, a novel vinca
alkaloid derivative, on delayed neuronal death using Mongolian gerbils. The animals were allowed to survive for 7 d after 3 or 5 min of forebrain
ischemia induced by bilateral occlusion of the common carotid arteries. Morphological changes and
calcium (45Ca) accumulation were evaluated in the CA1 sector of the hippocampus after
ischemia.
Vinconate (50, 100, and 300 mg/kg) showed protective effects against neuronal death in a dose-dependent manner when administered intraperitoneally (ip) 10 min before 5 min of
ischemia. However, the administration of
vinconate (100 and 300 mg/kg, ip) immediately after 5 min of
ischemia showed no
therapeutic effect, whereas a marked
therapeutic effect of
vinconate (50 and 100 mg/kg, ip) was observed when administered immediately after 3 min of
ischemia. An
anesthetic dose of
pentobarbital (40 mg/kg, ip) also produced significant protection against neuronal death. Furthermore, a 45Ca autoradiographic study indicated that a marked
calcium accumulation was found in the Ca1 sector at 7 d after 5 min of
ischemia, which was consistent with the extent of histological neuronal damage. When
vinconate (100 and 300 mg/kg, ip) was administered 10 min before 5 min of
ischemia, the abnormal
calcium accumulation was not detected in the CA1 sector. These data indicate that suppression of abnormal neuronal activity may be owing to the antagonistic action of
vinconate on
calcium accumulation.