EFFECT OF SYSTEMIC ZINC ADMINISTRATION ON DELAYED NEURONAL DEATH IN THE GERBIL HIPPOCAMPUS

The divalent cation zinc has been reported to possess several physiolo gical properties such as blocking apoptetic cell death through an inhi bitory effect on Ca2+-Mg2+ endonuclease activity, or modulating the ne urotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuro nal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neur onal cell death. Forty-five adult Mongolian gerbils of both sexes unde rwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcut aneously once, 1 h before ischemia (superacute group n = 6) or twice a t 24 and 48 h before ischemia (subacute group; n = 14). Histological s urvey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively co unting dead neurons in the CA1 sector. Subacute zinc pre-administratio n significantly reduced the nuclear damage and subsequent neuronal dea th; however, superacutely pre-administered zinc did not protect hippoc ampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogeno us zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.