Journal of Neuroimmune Pharmacology

, Volume 8, Issue 4, pp 1027–1036

Improved Visualization of Neuronal Injury Following Glial Activation by Manganese Enhanced MRI

  • Aditya N. Bade
  • Biyun Zhou
  • Adrian A. Epstein
  • Santhi Gorantla
  • Larisa Y. Poluektova
  • Jiangtao Luo
  • Howard E. Gendelman
  • Michael D. Boska
  • Yutong Liu
ORIGINAL ARTICLE

DOI: 10.1007/s11481-013-9475-3

Cite this article as:
Bade, A.N., Zhou, B., Epstein, A.A. et al. J Neuroimmune Pharmacol (2013) 8: 1027. doi:10.1007/s11481-013-9475-3

Abstract

Research directed at anatomical, integrative and functional activities of the central nervous system (CNS) can be realized through bioimaging. A wealth of data now demonstrates the utility of magnetic resonance imaging (MRI) towards unraveling complex neural connectivity operative in health and disease. A means to improve MRI sensitivity is through contrast agents and notably manganese (Mn2+). The Mn2+ ions enter neurons through voltage-gated calcium channels and unlike other contrast agents such as gadolinium, iron oxide, iron platinum and imaging proteins, provide unique insights into brain physiology. Nonetheless, a critical question that remains is the brain target cells serving as sources for the signal of Mn2+ enhanced MRI (MEMRI). To this end, we investigated MEMRI’s abilities to detect glial (astrocyte and microglia) and neuronal activation signals following treatment with known inflammatory inducing agents. The idea is to distinguish between gliosis (glial activation) and neuronal injury for the MEMRI signal and as such use the agent as a marker for neural activity in inflammatory and degenerative disease. We now demonstrate that glial inflammation facilitates Mn2+ neuronal ion uptake. Glial Mn2+ content was not linked to its activation. MEMRI performed on mice injected intracranially with lipopolysaccharide was associated with increased neuronal activity. These results support the notion that MEMRI reflects neuronal excitotoxicity and impairment that can occur through a range of insults including neuroinflammation. We conclude that the MEMRI signal enhancement is induced by inflammation stimulating neuronal Mn2+ uptake.

Keywords

Magnetic resonance imaging (MRI)Manganese enhanced MRI (MEMRI)BioimagingGlial activationMicrogliaAstrocyteGlial-neuronal interactionsInflammation

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Aditya N. Bade
    • 1
  • Biyun Zhou
    • 3
  • Adrian A. Epstein
    • 1
  • Santhi Gorantla
    • 1
  • Larisa Y. Poluektova
    • 1
  • Jiangtao Luo
    • 4
  • Howard E. Gendelman
    • 1
  • Michael D. Boska
    • 1
    • 2
  • Yutong Liu
    • 1
    • 2
  1. 1.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of RadiologyUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Department of Anesthesiology, Tongji Medical CollegeHuanzhong University of Science and TechnologyWuhanChina
  4. 4.Department of BiostatisticsUniversity of Nebraska Medical CenterOmahaUSA