Rapid disappearance of zinc positive terminals in focal brain ischemia.
The study was undertaken to determine if the levels of vesicular zinc in neuronal terminals would decrease in response to focal brain ischemia. The middle cerebral artery was occluded distal to the striatal branches in male spontaneously hypertensive rats. At 7, 15, 30, 45, 60, 90, 120 min; 3, 6, 12, 24, 48 h and 7 days later the animals were sacrificed and the brains were stained for zinc-sulfides, cell bodies and AChE-positive cholinergic fibers. The density of zinc positive terminals significantly decreased in the neocortical ischemic zone 7 min after middle cerebral artery occlusion (MCAO). In the neocortical layers II and III most zinc positive neuronal terminals disappeared at 7 min after MCAO whereas the zinc positive terminals in layers V and VI remained positive at least 2 h. Beginning at 1 h after MCAO and progressing to 24 h a significant decrease in the density of zinc positive terminals was observed in the dorsolateral striatum, and ventrobasal thalamic nucleus, both major projection areas of the sensorimotor cortex. The disappearance of zinc positive neuronal terminals in the ischemic neocortex and related areas, is most likely due to a neuronal release of vesicular zinc in response to hypoxia. The high extracellular concentration of zinc is thought to be both neuroprotective by blocking the NMDA receptor and neurotoxic by activating neuronal influx of Ca2+ through voltage gated calcium channels. It seems evident that the latter effect of zinc is contributing to the neuronal death in focal brain ischemia.
Sørensen
J C
JC
Department of Anatomy and Cytology, Institute of Medical Biology, University of Odense, Winslowparken 19, DK-5000, Odense C, Denmark.
Mattsson
B
B
Andreasen
A
A
Johansson
B B
BB
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D002539:Cerebral Arterial Diseases / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D019579:Neocortex / Q000098:blood supply*; D009411:Nerve Endings / Q000737:chemistry*; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D015032:Zinc / Q000032:analysis*
D015032:Zinc