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Tracking superparamagnetic iron oxide labeled monocytes in brain by high-field magnetic resonance imaging
Marina L Zelivyanskaya1, Jay A Nelson, Larissa Poluektova
1Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Abstract:
Inflammatory cells, most notably mononuclear phagocytes (MP; macrophages and microglia), play a critical role in brain homeostasis, repair and disease. One important event in cellular biodynamics is how MP move in and throughout the nervous system. Prior studies have focused principally on cell migration across the blood-brain barrier during neuroinflammatory processes with little work done on cell movement within the brain. During the past decade our laboratories have studied the role of MP in HIV-1-associated dementia (HAD). In HAD MP incite sustained glial inflammatory reactions causing significant neuronal damage. To extend these works we investigated cell movement in brain and its influence for disease in a novel co-registration system integrating neuropathology with high-field magnetic resonance imaging (MRI). Human monocytes labeled with superparamagnetic iron oxide particles were injected into the brain of severe combined immunodeficient (SCID) mice. MRI was recorded 1, 7, and 14 days after cell injection. MRI co-registered with histology verified that the MRI signal modification was due to the labeled cells. MRI showed human monocyte-derived macrophages along the injection site, the corpus callosum, the ventricular system and in other brain sites. These data support the idea that cell migration can be monitored in vivo and provides an opportunity to assess monocyte mobility in brain and its affects on neurodegenerative processes and notably HAD.
Insights
Researchers tracked the movement of human monocytes within the brain using MRI. This technique successfully monitored cell migration, offering insights into neurodegenerative diseases like HIV-1-associated dementia.
Area of Science:
- Neuroscience
- Immunology
- Medical Imaging
Background:
- Mononuclear phagocytes (MP), including macrophages and microglia, are crucial for brain health, repair, and disease.
- While MP migration across the blood-brain barrier is studied, their movement within the brain is less understood.
- Our lab investigates MP's role in HIV-1-associated dementia (HAD), where they drive inflammation and neuronal damage.
Purpose of the Study:
- To investigate cell movement within the brain and its impact on disease.
- To develop and utilize a novel system integrating neuropathology with high-field magnetic resonance imaging (MRI) for tracking cell migration in vivo.
Main Methods:
- Human monocytes were labeled with superparamagnetic iron oxide particles.
- Labeled cells were injected into the brains of severe combined immunodeficient (SCID) mice.
- Magnetic resonance imaging (MRI) was performed at 1, 7, and 14 days post-injection and co-registered with histology.
Main Results:
- MRI successfully detected signal modifications caused by the labeled cells.
- Co-registration with histology confirmed MRI signal changes corresponded to labeled cells.
- MRI visualized human monocyte-derived macrophages in various brain regions, including the injection site, corpus callosum, and ventricular system.
Conclusions:
- In vivo cell migration within the brain can be effectively monitored using MRI.
- This approach allows for the assessment of monocyte mobility in the brain.
- Understanding monocyte migration is vital for studying neurodegenerative processes, particularly in HAD.