AURINTRICARBOXYLIC ACID PROTECTS HIPPOCAMPAL-NEURONS FROM NMDA-INDUCED AND ISCHEMIA-INDUCED TOXICITY INVIVO

The Polymeric dye aurintricarboxylic acid (ATA) has been shown to Prot ect various cell types from apoptotic cell death, reportedly through i nhibition of a calcium-dependent endonuclease activity. Recent studies have indicated that there may be some commonalities among apoptosis, programmed cell death, and certain other forms of neuronal death. To b egin to explore the possibility of common biochemical mechanisms under lying ischemia- or excitotoxin-induced neuronal death and apoptosis in vivo, gerbils or rats subjected to transient global ischemia or NMDA microinjection, respectively, received a simultaneous intracerebral in fusion of ATA or vehicle. As a biochemical marker of neuronal death, s pectrin proteolysis, which is mediated by activation of calpain I, was measured in hippocampus after 24 h. ATA treatment resulted in a profo und reduction of both NMDA- and ischemia-induced spectrin proteolysis, consistent with the possibility of some common mechanism in apoptosis and other forms of neuronal death in vivo.