Neurotherapeutics

, Volume 13, Issue 3, pp 635–646

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson’s Disease

  • Katherine E. Olson
  • Aditya N. Bade
  • Charles R. Schutt
  • Jingdong Dong
  • Scott J. Shandler
  • Michael D. Boska
  • R. Lee Mosley
  • Howard E. Gendelman
  • Yutong Liu
Original Article

DOI: 10.1007/s13311-016-0449-z

Cite this article as:
Olson, K.E., Bade, A.N., Schutt, C.R. et al. Neurotherapeutics (2016) 13: 635. doi:10.1007/s13311-016-0449-z

Abstract

Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson’s disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

Key Words

Magnetic resonance imaging (MRI) manganese enhanced MRI (MEMRI) MPTP inflammation glial activation neuroprotection 

Supplementary material

13311_2016_449_MOESM1_ESM.pdf (1.2 mb)
ESM 1(PDF 1225 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  • Katherine E. Olson
    • 1
  • Aditya N. Bade
    • 1
  • Charles R. Schutt
    • 1
  • Jingdong Dong
    • 2
  • Scott J. Shandler
    • 3
  • Michael D. Boska
    • 1
    • 2
  • R. Lee Mosley
    • 1
  • Howard E. Gendelman
    • 1
  • 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.Longevity BiotechPhiladelphiaUSA

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