Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus.
The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca(2+)-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n = 6) or twice at 24 and 48 h before ischemia (subacute group; n = 14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.
Matsushita
K
K
Fifth Department of Internal Medicine, Hyogo College of Medicine, Japan.
Kitagawa
K
K
Matsuyama
T
T
Ohtsuki
T
T
Taguchi
A
A
Mandai
K
K
Mabuchi
T
T
Yagita
Y
Y
Yanagihara
T
T
Matsumoto
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D004706:Endodeoxyribonucleases; C029367:calcium magnesium dependent endodeoxyribonuclease; D015032:Zinc