Inosine and guanosine presence neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia

Murine spinal cord primary mixed cultures were treated with the respiratory inhibitor, rotenone, to mimic hypoxic conditions. Under these conditions n eurons rapidly underwent oncosis (necrosis) with a complete loss in viabili ty occurring within 260 min; however, astrocytes, which accounted for most of the cell population, died more slowly with 50% viability occurring at 56 5 min. Inosine preserved both total cell and neuronal viability in a concen tration-dependent manner. The time of inosine addition relative to hypoxic insult was critical with the most effective protection occurring when inosi ne was added just prior to or within 5 min after insult. Inosine was ineffe ctive when added 30 min after hypoxic insult. The effect of guanosine was s imilar to that of inosine. Treatment of cultures with BCX-34, a purine nucl eoside phosphorylase inhibitor, prevented protection by inosine or guanosin e, suggesting involvement of a purine nucleoside phosphorylase in the nucle oside protective effect. (C) 1999 Elsevier Science B.V. All rights reserved .