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 E.
AU - Boska, Michael D.
AU - Liu, Yutong
N1 - Funding Information:
This study is supported by the National Institutes of Health (NIH) grants K25 MH089851, R24 OD018546-01, P01 DA028555, R01 NS36126, P01 NS031492, R01 NS034239, P01 MH64570, P01 NS043985, P30 MH062261, and R01 AG043540, a grant from the Nebraska Research Initiative, and University of Nebraska Medical Center Graduate Student Fellowship.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
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 -