title: Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults.
abstract: OBJECTIVE
  To examine the long-term consequences of manganese exposure due to the use of manganese-enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid-percussion injury (FPI) model.
  
  
  METHODS
  Two groups of adult male Wistar rats (n = 72) were studied with either MEMRI, whereby rats receive MnCl(2) (100 mg/kg intraperitoneally) 24 hours prior to scanning, or standard MRI (sMRI) with no contrast agent. Rats from both groups underwent FPI or sham injury and were longitudinally assessed for 6 months for neurological toxicity using behavioral tests, EEG recording, and MRI scanning.
  
  
  RESULTS
  Regardless of whether they received FPI, MEMRI animals showed progressive signs of cerebral toxicity compared with sMRI rats, including significantly reduced weight gain, progressive brain volume decrease, and increased anxiety and depressive-like behaviors.
  
  
  CONCLUSIONS
  Long-term structural and functional consequences of using manganese as a contrast agent for MRI can confound experimental outcomes and must be taken into account when designing longitudinal imaging studies using manganese-enhanced MRI.
authors.affiliation: Department of Medicine (RMH), University of Melbourne, Victoria, Australia.
authors.forename: Viviane
authors.initials: V
authors.lastname: Bouilleret
authors.forename: Lisa
authors.initials: L
authors.lastname: Cardamone
authors.forename: Cyril
authors.initials: C
authors.lastname: Liu
authors.forename: Amelia S
authors.initials: AS
authors.lastname: Koe
authors.forename: Ke
authors.initials: K
authors.lastname: Fang
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
authors.forename: Damian E
authors.initials: DE
authors.lastname: Myers
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Jones
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000175:diagnosis* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D003287:Contrast Media / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D007089:Image Enhancement / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000009:adverse effects / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000009:adverse effects*; D020149:Manganese Poisoning / Q000175:diagnosis*; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000175:diagnosis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
chemical_list: D003287:Contrast Media; D017895:Manganese Compounds