Dose-response features of neuroprotective agents: an integrative summary.

This article provides an integrative summary of the effects of neuroprotective agents on neuronal survival and neurite outgrowth using primary cell cultures, multiple neuronal cell lines, and astroglial cells. These findings are dealt with in considerable detail in the following three articles (Calabrese, 2008a, 2008b, 2008c) of this series of issues of Critical Reviews in Toxicology. The principal finding is that the overwhelming majority of neuroprotective agents display biphasic dose responses, characterized by modest low-dose enhancement/stimulation and high-dose inhibitory responses. The quantitative features of these dose responses are consistent with the hormetic dose-response model. Mechanisms that account for numerous hormetic dose responses of neuroprotective agents are summarized, as well as the clinical implications of specific experimental findings.