6-Aminonicotinamide selectively causes necrosis in reactive astroglia cells in vivo

6-Aminonicotinamide (6-AN) is a potent antimetabolite of nicotinamide. Previous studies show a selective gliotoxic effect of 6-AN in nontraumatized nervous system. The present study was undertaken to determine if 6-AN can be selectively toxic against reactive (vs. nonreactive) glial cells distal to site of crush in rat optic nerve. Previously conducted studies indicate that glial cells in crushed optic nerves undergo marked biochemical changes during the second post-operative week. In the present study, 6-AN was administered by i.p. injection 5 days after right optic nerve crush in doses of either 5 or 10 mg/kg body weight. Rats were killed 2 days after injection. High doses of 6-AN resulted in loss of astrocytes and intracellular glial edema in both crushed and unoperated optic nerve. Results were more dramatic in traumatized nerve. Low doses caused degenerative glial changes in reactive, but not in unoperated optic nerve. Injection of 5 mg doses of 6-AN at 13 days post-operatively caused degeneration of reactive astrocytes. The possibility of using 6-AN to selectively kill highly metabolic reactive astrocytes after CNS injury is discussed.