title: A time-course analysis of changes in cerebral metal levels following a controlled cortical impact.
abstract: Traumatic brain injury (TBI) is complicated by a sudden and dramatic change in brain metal levels, including iron (Fe), copper (Cu) and zinc (Zn). Specific 'metallo-pathological' features of TBI include increased non-heme bound Fe and the liberation of free Zn ions, both of which may contribute to the pathogenesis of TBI. To further characterise the metal dyshomeostasis that occurs following brain trauma, we performed a quantitative time-course survey of spatial Fe, Cu and Zn distribution in mice receiving a controlled cortical impact TBI. Images of brain metal levels produced using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in the upper quadrant of the ipsilateral hemisphere were compared to the corresponding contralateral hemisphere, together with regional areas radiating toward the center of the brain from the site of lesion. Significant regional and time point specific elevations in Fe, Zn and Cu were detected immediately and up to 28 days after TBI. The magnitude and timeframe of many of these changes suggest that TBI results in a pronounced and sustained alteration in normal metal levels within the brain. Such alterations are likely to play a role in both the short- and long-term consequences of head trauma and suggest that pharmacological modulation to normalize these metal levels may be efficacious in improving functional outcome.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria 3052, Australia. paul.adlard@florey.edu.au.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Portbury
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria 3052, Australia. paul.adlard@florey.edu.au and Elemental Bio-imaging Facility, University of Technology Sydney, Thomas Street, Broadway, New South Wales 2007, Australia.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria 3052, Australia. paul.adlard@florey.edu.au.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sgambelloni
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria 3052, Australia. paul.adlard@florey.edu.au.
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria 3052, Australia. paul.adlard@florey.edu.au.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D019216:Metals, Heavy / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D013997:Time Factors
chemical_list: D019216:Metals, Heavy