Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain

Aditya N. Bade, Biyun Zhou, JoEllyn M McMillan, Prabagaran Narayanasamy, Ram Veerubhotla, Howard Eliot Gendelman, Michael D. Boska, Yutong Liu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Manganese (Mn<sup>2+</sup>)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn<sup>2+</sup> is relatively long with a half-life (t<inf>1/2</inf>) of 51-74 days causing a slow decline of MRI signal enhancement following Mn<sup>2+</sup> administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn<sup>2+</sup> from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn<sup>2+</sup> enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New methodsWe investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn<sup>2+</sup>, could affect the decline of Mn<sup>2+</sup> induced MRI enhancement in brain. Results and conclusionTwo-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn<sup>2+</sup> induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with existing methodsTo the best of our knowledge, no method exists to accelerate the decline of the Mn<sup>2+</sup> induced MRI enhancement for repeated MEMRI tests.

Original languageEnglish (US)
Pages (from-to)92-98
Number of pages7
JournalJournal of Neuroscience Methods
Volume251
DOIs
StatePublished - Aug 5 2015

Fingerprint

Aminosalicylic Acid
Manganese
Rodentia
Brain
Animal Diseases
Chelating Agents
Half-Life
Central Nervous System
acetyl 4-aminosalicylic acid

Keywords

  • Chelation
  • Manganese enhanced MRI (MEMRI)
  • N-acetylated-para-aminosalicylic acid (AcPAS)
  • Repeated MEMRI

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{df846a9565c344e5856539fc675a1d94,
title = "Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain",
abstract = "Manganese (Mn2+)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn2+ is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn2+ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn2+ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn2+ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New methodsWe investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn2+, could affect the decline of Mn2+ induced MRI enhancement in brain. Results and conclusionTwo-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn2+ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100{\%} to 17{\%} in AcPAS treated mice, while in PBS controls the decline is from 100{\%} to 27{\%}. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with existing methodsTo the best of our knowledge, no method exists to accelerate the decline of the Mn2+ induced MRI enhancement for repeated MEMRI tests.",
keywords = "Chelation, Manganese enhanced MRI (MEMRI), N-acetylated-para-aminosalicylic acid (AcPAS), Repeated MEMRI",
author = "Bade, {Aditya N.} and Biyun Zhou and McMillan, {JoEllyn M} and Prabagaran Narayanasamy and Ram Veerubhotla and Gendelman, {Howard Eliot} and Boska, {Michael D.} and Yutong Liu",
year = "2015",
month = "8",
day = "5",
doi = "10.1016/j.jneumeth.2015.05.013",
language = "English (US)",
volume = "251",
pages = "92--98",
journal = "Journal of Neuroscience Methods",
issn = "0165-0270",
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TY - JOUR

T1 - Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain

AU - Bade, Aditya N.

AU - Zhou, Biyun

AU - McMillan, JoEllyn M

AU - Narayanasamy, Prabagaran

AU - Veerubhotla, Ram

AU - Gendelman, Howard Eliot

AU - Boska, Michael D.

AU - Liu, Yutong

PY - 2015/8/5

Y1 - 2015/8/5

N2 - Manganese (Mn2+)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn2+ is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn2+ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn2+ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn2+ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New methodsWe investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn2+, could affect the decline of Mn2+ induced MRI enhancement in brain. Results and conclusionTwo-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn2+ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with existing methodsTo the best of our knowledge, no method exists to accelerate the decline of the Mn2+ induced MRI enhancement for repeated MEMRI tests.

AB - Manganese (Mn2+)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn2+ is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn2+ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn2+ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn2+ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New methodsWe investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn2+, could affect the decline of Mn2+ induced MRI enhancement in brain. Results and conclusionTwo-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn2+ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with existing methodsTo the best of our knowledge, no method exists to accelerate the decline of the Mn2+ induced MRI enhancement for repeated MEMRI tests.

KW - Chelation

KW - Manganese enhanced MRI (MEMRI)

KW - N-acetylated-para-aminosalicylic acid (AcPAS)

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