Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice

Aditya N. Bade, Santhi Gorantla, Prasanta K. Dash, Edward Makarov, Balasrinivasa R Sajja, Larisa Y Poluektova, Jiangtao Luo, Howard Eliot Gendelman, Michael D. Boska, Yutong Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence. Despite decades of research, there remain no biomarkers for HAND and all potential comorbid conditions must first be excluded for a diagnosis to be made. To this end, we now report that manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγcnull humanized mice. MEMRI diagnostics mirrors the abilities of Mn2+ to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn2+ activities in neurons. In 16-week virus-infected humanized mice, altered MEMRI signal enhancement was easily observed in affected brain regions. These included, but were not limited to, the hippocampus, amygdala, thalamus, globus pallidus, caudoputamen, substantia nigra, and cerebellum. MEMRI signal was coordinated with levels of HIV-1 infection, neuroinflammation (astro- and micro-gliosis), and neuronal injury. MEMRI accurately demonstrates the complexities of HIV-1-associated neuropathology in rodents that reflects, in measure, the clinical manifestations of neuroAIDS as it is seen in a human host.

Original languageEnglish (US)
Pages (from-to)3286-3297
Number of pages12
JournalMolecular Neurobiology
Volume53
Issue number5
DOIs
StatePublished - Jul 1 2016

Fingerprint

Virus Diseases
Manganese
Magnetic Resonance Imaging
Pathology
Brain
Gliosis
HIV
Viruses
Neurons
Globus Pallidus
Aptitude
Substantia Nigra
Amygdala
Thalamus
Cerebellum
Bruton type agammaglobulinemia
Rodentia
Hippocampus
Biomarkers
Wounds and Injuries

Keywords

  • Biomarkers
  • HIV-1 neuropathology
  • Humanized mice
  • Manganese-enhanced MRI (MEMRI)
  • Neuroinflammation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice. / Bade, Aditya N.; Gorantla, Santhi; Dash, Prasanta K.; Makarov, Edward; Sajja, Balasrinivasa R; Poluektova, Larisa Y; Luo, Jiangtao; Gendelman, Howard Eliot; Boska, Michael D.; Liu, Yutong.

In: Molecular Neurobiology, Vol. 53, No. 5, 01.07.2016, p. 3286-3297.

Research output: Contribution to journalArticle

@article{d86bf1aaf5904678ada63bcffa436f47,
title = "Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice",
abstract = "Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence. Despite decades of research, there remain no biomarkers for HAND and all potential comorbid conditions must first be excluded for a diagnosis to be made. To this end, we now report that manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγcnull humanized mice. MEMRI diagnostics mirrors the abilities of Mn2+ to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn2+ activities in neurons. In 16-week virus-infected humanized mice, altered MEMRI signal enhancement was easily observed in affected brain regions. These included, but were not limited to, the hippocampus, amygdala, thalamus, globus pallidus, caudoputamen, substantia nigra, and cerebellum. MEMRI signal was coordinated with levels of HIV-1 infection, neuroinflammation (astro- and micro-gliosis), and neuronal injury. MEMRI accurately demonstrates the complexities of HIV-1-associated neuropathology in rodents that reflects, in measure, the clinical manifestations of neuroAIDS as it is seen in a human host.",
keywords = "Biomarkers, HIV-1 neuropathology, Humanized mice, Manganese-enhanced MRI (MEMRI), Neuroinflammation",
author = "Bade, {Aditya N.} and Santhi Gorantla and Dash, {Prasanta K.} and Edward Makarov and Sajja, {Balasrinivasa R} and Poluektova, {Larisa Y} and Jiangtao Luo and Gendelman, {Howard Eliot} and Boska, {Michael D.} and Yutong Liu",
year = "2016",
month = "7",
day = "1",
doi = "10.1007/s12035-015-9258-3",
language = "English (US)",
volume = "53",
pages = "3286--3297",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "5",

}

TY - JOUR

T1 - Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice

AU - Bade, Aditya N.

AU - Gorantla, Santhi

AU - Dash, Prasanta K.

AU - Makarov, Edward

AU - Sajja, Balasrinivasa R

AU - Poluektova, Larisa Y

AU - Luo, Jiangtao

AU - Gendelman, Howard Eliot

AU - Boska, Michael D.

AU - Liu, Yutong

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence. Despite decades of research, there remain no biomarkers for HAND and all potential comorbid conditions must first be excluded for a diagnosis to be made. To this end, we now report that manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγcnull humanized mice. MEMRI diagnostics mirrors the abilities of Mn2+ to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn2+ activities in neurons. In 16-week virus-infected humanized mice, altered MEMRI signal enhancement was easily observed in affected brain regions. These included, but were not limited to, the hippocampus, amygdala, thalamus, globus pallidus, caudoputamen, substantia nigra, and cerebellum. MEMRI signal was coordinated with levels of HIV-1 infection, neuroinflammation (astro- and micro-gliosis), and neuronal injury. MEMRI accurately demonstrates the complexities of HIV-1-associated neuropathology in rodents that reflects, in measure, the clinical manifestations of neuroAIDS as it is seen in a human host.

AB - Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence. Despite decades of research, there remain no biomarkers for HAND and all potential comorbid conditions must first be excluded for a diagnosis to be made. To this end, we now report that manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγcnull humanized mice. MEMRI diagnostics mirrors the abilities of Mn2+ to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn2+ activities in neurons. In 16-week virus-infected humanized mice, altered MEMRI signal enhancement was easily observed in affected brain regions. These included, but were not limited to, the hippocampus, amygdala, thalamus, globus pallidus, caudoputamen, substantia nigra, and cerebellum. MEMRI signal was coordinated with levels of HIV-1 infection, neuroinflammation (astro- and micro-gliosis), and neuronal injury. MEMRI accurately demonstrates the complexities of HIV-1-associated neuropathology in rodents that reflects, in measure, the clinical manifestations of neuroAIDS as it is seen in a human host.

KW - Biomarkers

KW - HIV-1 neuropathology

KW - Humanized mice

KW - Manganese-enhanced MRI (MEMRI)

KW - Neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=84930802768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930802768&partnerID=8YFLogxK

U2 - 10.1007/s12035-015-9258-3

DO - 10.1007/s12035-015-9258-3

M3 - Article

C2 - 26063593

AN - SCOPUS:84930802768

VL - 53

SP - 3286

EP - 3297

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 5

ER -