Magnetic Labeling of Activated Microglia in Experimental Gliomas

Abstract

Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS.

‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

“…Of high relevance for clinical applications, PEG-coated nanoparticle accumulation is enhanced in pathological foci including gliosarcoma and Multiple Sclerosis models [17,18], possibly due to inflammation-induced BBB hyperpermeability -similar to enhanced nanoparticle permeability/retention (EPR effect) in brain tumors [19]. [20,21] exhibiting dramatically more rapid/extensive nanoparticle uptake than all other neural subtypes, in vitro [22] and in vivo [23]. This constitutes a significant 'extracellular barrier' to particle uptake by other neural cell types by 'out-competing' them [22].…”

Differences in Magnetic Particle Uptake by CNS Neuroglial Subclasses: Implications for Neural Tissue Engineering

“…A small number of studies have reported MP uptake by neuroglial cells [25,26] but no study to date has systematically compared particle uptake and handling by individual neuroglial subclasses. Here, we have assessed the uptake and intracellular processing of a single type of MP (of specific size and formulation) by oligodendrocyte lineage cells ie.…”

It's not just about anatomy: In vivo bioluminescence imaging as an eyepiece into biology

“…At the interface of these fields are applications that employ a variety of imaging modalities, including magnetic resonance imaging (MRI) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), the use of radionuclide tracers in positron emission tomography (PET) and single photon emission tomography (SPECT) (16 -25), x-ray computed tomography (CT) (26,27), and optical methods (2,5,28 -40). This nascent area of investigation is rapidly gaining acceptance in diverse fields, such as cancer biology, immunology, gene therapy, and microbiology.…”