title: Manganese transport in the rat optic nerve evaluated with spatial- and time-resolved magnetic resonance imaging.
abstract: OBJECTIVE
  1) To evaluate a novel theoretical model for in vivo axonal Mn(2+) transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data.
  
  
  METHODS
  Time-resolved in vivo T(1)-weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n = 9) ON was obtained at different timepoints after intravitreal MnCl(2) injection. A concentration-dependent and a rate-dependent function for the Mn(2+) retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data.
  
  
  RESULTS
  The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn(2+) concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model.
  
  
  CONCLUSIONS
  The results indicate that Mn(2+) input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn(2+) transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly.
authors.affiliation: Department of Radiography, Sør-Trøndelag University College, Trondheim, Norway. oystein.olsen@ntnu.no
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Olsen
authors.forename: Anders
authors.initials: A
authors.lastname: Kristoffersen
authors.forename: Marte
authors.initials: M
authors.lastname: Thuen
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.forename: Christian
authors.initials: C
authors.lastname: Brekken
authors.forename: Olav
authors.initials: O
authors.lastname: Haraldseth
authors.forename: Pål Erik
authors.initials: PE
authors.lastname: Goa
mesh_terms: D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D005260:Female; D007091:Image Processing, Computer-Assisted; D058449:Intravitreal Injections; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000493:pharmacokinetics*; D023421:Models, Animal; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism*; D011868:Radioisotopes / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D012680:Sensitivity and Specificity
chemical_list: D011868:Radioisotopes; D008345:Manganese