Loss of cellular calcium homeostasis or the production of nitric oxide
(NO) have been cited as possible mechanisms that may contribute to ne
uronal degeneration during ischemia. We therefore examined whether cel
lular calcium blockade, using the agent HA1077, was protective during
anoxia in hippocampal neuronal cell cultures, and whether the in vitro
effects of this drug were linked to the NO pathway. Administration of
the agent during anoxia was neuroprotective in neuronal cell culture.
In contrast, HA1077 did not protect hippocampal neurons during NO exp
osure. In addition, inhibition of NO synthesis in conjunction with HA1
077 application during anoxia did not significantly increase survival
beyond the maximum protection afforded by HA1O77 alone. These results
suggest that calcium may be an initial messenger in the ischemic casca
de, but that subsequent neuronal degeneration is dependent upon the NO
pathway.