Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent

Fuminori Hyodo, Kai Hsiang Chuang, Artem G. Goloshevsky, Agnieszka Sulima, Gary L. Griffiths, James B. Mitchell, Alan P. Koretsky, Murali C. Krishna

    Research output: Contribution to journalArticle

    67 Citations (Scopus)

    Abstract

    Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood-brain barrier (BBB)-permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T1-mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1-oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9±0.35 and 3.0±0.50 mmol/L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.

    Original languageEnglish
    Pages (from-to)1165-1174
    Number of pages10
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume28
    Issue number6
    DOIs
    Publication statusPublished - Jun 30 2008

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    Blood-Brain Barrier
    Neuroimaging
    Contrast Media
    Oxidation-Reduction
    Magnetic Resonance Imaging
    Antioxidants
    Thalamus
    Cerebral Cortex
    Reactive Oxygen Species
    Brain
    Injections
    Middle Cerebral Artery Infarction
    Electron Spin Resonance Spectroscopy
    Amyotrophic Lateral Sclerosis
    Brain Diseases
    Nervous System Diseases
    Reperfusion
    Rodentia
    Spectrum Analysis
    Stroke

    All Science Journal Classification (ASJC) codes

    • Neurology
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

    Cite this

    Hyodo, F., Chuang, K. H., Goloshevsky, A. G., Sulima, A., Griffiths, G. L., Mitchell, J. B., ... Krishna, M. C. (2008). Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent. Journal of Cerebral Blood Flow and Metabolism, 28(6), 1165-1174. https://doi.org/10.1038/jcbfm.2008.5

    Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent. / Hyodo, Fuminori; Chuang, Kai Hsiang; Goloshevsky, Artem G.; Sulima, Agnieszka; Griffiths, Gary L.; Mitchell, James B.; Koretsky, Alan P.; Krishna, Murali C.

    In: Journal of Cerebral Blood Flow and Metabolism, Vol. 28, No. 6, 30.06.2008, p. 1165-1174.

    Research output: Contribution to journalArticle

    Hyodo, F, Chuang, KH, Goloshevsky, AG, Sulima, A, Griffiths, GL, Mitchell, JB, Koretsky, AP & Krishna, MC 2008, 'Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent', Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 6, pp. 1165-1174. https://doi.org/10.1038/jcbfm.2008.5
    Hyodo F, Chuang KH, Goloshevsky AG, Sulima A, Griffiths GL, Mitchell JB et al. Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent. Journal of Cerebral Blood Flow and Metabolism. 2008 Jun 30;28(6):1165-1174. https://doi.org/10.1038/jcbfm.2008.5
    Hyodo, Fuminori ; Chuang, Kai Hsiang ; Goloshevsky, Artem G. ; Sulima, Agnieszka ; Griffiths, Gary L. ; Mitchell, James B. ; Koretsky, Alan P. ; Krishna, Murali C. / Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent. In: Journal of Cerebral Blood Flow and Metabolism. 2008 ; Vol. 28, No. 6. pp. 1165-1174.
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