title: Longitudinal Assessments of Normal and Perilesional Tissues in Focal Brain Ischemia and Partial Optic Nerve Injury with Manganese-enhanced MRI.
abstract: Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days. Intravitreal Mn administration to healthy rodents not only allowed tracing of primary visual pathways, but also enhanced the hippocampus and medial amygdala within a day, whereas partial transection of the optic nerve led to MRI detection of degrading anterograde Mn transport at the primary injury site and the perilesional tissues secondarily over 6 weeks. Taken together, our results indicate the different Mn transport dynamics across widespread projections in normal and diseased brains. Particularly, perilesional brain tissues may attract abnormal Mn accumulation and gradually reduce anterograde Mn transport via specific Mn entry routes.
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania, United States.|Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|New York University (NYU) Langone Eye Center, NYU Langone Medical Center, Department of Ophthalmology, NYU School of Medicine, New York, New York, United States.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Chan
authors.affiliation: Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.|Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States.
authors.forename: Iris Y
authors.initials: IY
authors.lastname: Zhou
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Liu
authors.affiliation: NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.|Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Yolandi
authors.initials: Y
authors.lastname: van der Merwe
authors.affiliation: Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Fan
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Victor K
authors.initials: VK
authors.lastname: Hung
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.|Department of Ophthalmology, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Sookja K
authors.initials: SK
authors.lastname: Chung
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Wu-Tian
authors.initials: WT
authors.lastname: Wu
authors.affiliation: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.|Department of Ophthalmology, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.|School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000473:pathology*; D004195:Disease Models, Animal; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D020221:Optic Nerve Injuries / Q000000981:diagnostic imaging* / Q000473:pathology*; D017207:Rats, Sprague-Dawley
chemical_list: D008345:Manganese