Use of zinc as a treatment for traumatic brain injury in the rat: effects on cognitive and behavioral outcomes

Neurorehabil Neural Repair. 2012 Sep;26(7):907-13. doi: 10.1177/1545968311435337. Epub 2012 Feb 13.

Abstract

Background: While treatments for the behavioral deficits associated with traumatic brain injury (TBI) are currently limited, animal models suggest that zinc supplementation may increase resilience to TBI.

Objective: This work tests the hypothesis that zinc supplementation after TBI can be used as treatment to improve behavioral outcomes such as anxiety, depression, and learning and memory.

Methods: TBI was induced by controlled cortical impact to the medial frontal cortex. After TBI, rats were fed either a zinc adequate (ZA, 30 ppm) or zinc supplemented (ZS, 180 ppm) diet. Additional rats in each dietary group (ZA or ZS) were given a single intraperitoneal (ip) injection of zinc (30 mg/kg) 1 hour following injury.

Results: Brain injury resulted in significant increases in anxiety-like and depression-like behaviors as well as impairments in learning and memory. None of the zinc treatments (dietary or ip zinc) improved TBI-induced anxiety. The 2-bottle saccharin preference test for anhedonia revealed that dietary ZS also did not improve depression-like behaviors. However, dietary ZS combined with an early ip zinc injection significantly reduced anhedonia (P < .001). Dietary supplementation after injury, but not zinc injection, significantly improved (P < .05) cognitive behavior as measured by the time spent finding the hidden platform in the Morris water maze test compared with injured rats fed a ZA diet.

Conclusions: These data suggest that zinc supplementation may be an effective treatment option for improving behavioral deficits such as cognitive impairment and depression following TBI.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anhedonia / physiology
  • Animals
  • Anxiety / diet therapy
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Behavior, Animal / physiology*
  • Brain Injuries / diet therapy
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Cognition Disorders / diet therapy
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / physiopathology
  • Combined Modality Therapy
  • Depression / diet therapy
  • Depression / drug therapy*
  • Depression / physiopathology
  • Disease Models, Animal
  • Injections
  • Neuropsychological Tests
  • Rats
  • Rats, Sprague-Dawley
  • Saccharin
  • Zinc / administration & dosage*
  • Zinc / therapeutic use

Substances

  • Saccharin
  • Zinc