Zinc in traumatic brain injury: from neuroprotection to neurotoxicity.
OBJECTIVE
In light of the recent recognition that even mild forms of traumatic brain injury (TBI) can lead to long-term cognitive and behavioral deficits, this review examines recent data on the neuroprotective and neurotoxic roles of zinc after brain injury.


RESULTS
Data show that treatment using dietary and parenteral zinc supplementation can reduce TBI-associated depression and improve cognitive function, specifically spatial learning and memory. However, excessive release of free zinc, particularly in the hippocampus associated with acute injury, can lead to increases in protein ubiquitination and neuronal death.


CONCLUSIONS
This work shows the need for future research to clarify the potentially contradictory roles of zinc in the hippocampus and define the clinical use of zinc as a treatment following brain injury in humans. This is particularly important given the finding that zinc may reduce TBI-associated depression, a common and difficult outcome to treat in all forms of TBI.
aDepartment of Biomedical Sciences bProgram in Neuroscience, Florida State University College of Medicine, Tallahassee, Florida, USA.
Deborah R
DR
Morris
Cathy W
CW
Levenson
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D016923:Cell Death / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology; D015032:Zinc / Q000008:administration & dosage* / Q000009:adverse effects*
D018696:Neuroprotective Agents; D015032:Zinc