Zinc translocation accelerates infarction after mild transient focal ischemia.

Abstract

Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

• Authors: J-M Lee, G J Zipfel, K H Park, Y Y He, C Y Hsu, D W Choi
• Journal: Neuroscience (Neuroscience) Vol. 115 Issue 3 Pg. 871-8 ( 2002) ISSN: 0306-4522 [Print] United States
• PMID: 12435425 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aminoquinolines
• Chelating Agents
• Fluorescent Dyes
• Tosyl Compounds
• N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide
• Casp3 protein, rat
• Caspase 3
• Caspases
• Zinc

Topics

• Aminoquinolines
• Animals
• Caspase 3
• Caspases (metabolism)
• Cerebral Infarction (metabolism, pathology, physiopathology)
• Chelating Agents (pharmacology)
• Fluorescent Dyes
• Immunohistochemistry
• Ischemic Attack, Transient (metabolism, pathology, physiopathology)
• Male
• Nerve Degeneration (metabolism, pathology, physiopathology)
• Neurons (metabolism, pathology)
• Presynaptic Terminals (metabolism)
• Rats
• Rats, Long-Evans
• Synaptic Transmission (physiology)
• Telencephalon (metabolism, pathology, physiopathology)
• Tosyl Compounds
• Zinc (metabolism)