Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury.
Prior evidence indicates that synaptically-released zinc enters postsynaptic neurons in toxic excess during ischemia and seizures. In addition, prevention of this zinc translocation has been shown to be neuroprotective in both ischemia and seizures. Here we show evidence that the same translocation of zinc from presynaptic boutons into postsynaptic neurons occurs after mechanical injury to the brain. Specifically, using a rat model of traumatic brain injury, we show that trauma is associated with (i) loss of zinc from presynaptic boutons (ii) appearance of zinc in injured neurons, and (iii) neuroprotection by intraventricular administration of a zinc chelator just prior to brain impact. The possible use of zinc chelators for neuroprotection after head trauma is considered.
Suh
S W
SW
Center for Biomedical Engineering, UTMB, Galveston, TX 77555, USA.
Chen
J W
JW
Motamedi
M
M
Bell
B
B
Listiak
K
K
Pons
N F
NF
Danscher
G
G
Frederickson
C J
CJ
D000634:Aminoquinolines; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000378:metabolism*; D014105:Tosyl Compounds; D015032:Zinc / Q000032:analysis / Q000493:pharmacokinetics*
D000634:Aminoquinolines; D002614:Chelating Agents; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D014105:Tosyl Compounds; C061730:N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide; D004492:Edetic Acid; D015032:Zinc