Abstract: Neuroimaging technology allowed researchers to capture the activity of microglia and astrocytes in the brain. The researchers were able to quantify alterations in the morphology of different cell populations involved in neuroinflammation.
Source: CSIC
The laboratory research led by Dr. Silvia de Santis and Dr. Santiago Canals, both of the Institute of Neurosciences UMH-CSIC (Alicante, Spain), has allowed to visualize for the first time and in great detail the cerebral inflammation by means of the diffusion. -Weighted MRI image.
This detailed “x-ray” of inflammation cannot be obtained with conventional MRI, but requires data acquisition sequences and special mathematical models.
Once the method was developed, the researchers were able to quantify the alterations in the morphology of the different cell populations involved in the inflammatory process of the brain.
An innovative strategy developed by researchers has made possible this important breakthrough, which is published today in the journal Science Advances and may be crucial in changing the course of the study and treatment of neurodegenerative diseases.
The research, the first author of which is Raquel Garcia-Hernández, shows that diffusion-weighted MRI can detect in a non-invasive and differential way the activation of microglia and astrocytes, two types of brain cells that are they are at the root of neuroinflammation and its progression.
Degenerative brain diseases such as Alzheimer’s and other dementias, Parkinson’s or multiple sclerosis are an urgent and difficult problem to address. Sustained activation of two types of brain cells, microglia and astrocytes leads to chronic inflammation in the brain which is one of the causes of neurodegeneration and contributes to its progression.
However, there is a lack of non-invasive approaches that can specifically characterize brain inflammation in vivo. The current gold standard is positron emission tomography (PET), but it is difficult to generalize and is associated with exposure to ionizing radiation, so its use is limited in vulnerable populations and in studies. longitudinal, which require the use of PET repeatedly over a period of time. years, as is the case with neurodegenerative diseases.
Another drawback of PET is its low spatial resolution, which makes it unsuitable for the image of small structures, with the added drawback that specific inflammation radiolacers are expressed in multiple cell types (microglia, microglia, astrocytes and endothelium), which makes them indistinguishable.
Faced with these drawbacks, diffusion-weighted MRI has the unique ability to imagine the microstructure of the brain in vivo in a non-invasive, high-resolution way by capturing the random movement of water molecules in the brain parenchyma to generate contrast in images. MRI.
INNOVATIVE STRATEGY
In this study, researchers at the UMH-CSIC Institute of Neuroscience have developed an innovative strategy that allows images of the activation of microglia and astrocytes in the gray matter of the brain by diffusion-weighted magnetic resonance imaging (dw-MRI). .
“This is the first time it has been shown that the signal of this type of magnetic resonance imaging (dw-MRI) can detect the activation of microglia and astrocytes, with specific footprints for each cell population. This strategy we have used reflects the morphological changes validated post mortem by quantitative immunohistochemistry, “the researchers note.
They have also shown that this technique is sensitive and specific for detecting inflammation with and without neurodegeneration, so both conditions can be differentiated. In addition, it allows to discriminate between inflammation and demyelination characteristic of multiple sclerosis.
This work has also been able to demonstrate the translational value of the approach used in a high-resolution cohort of healthy humans, “in which we performed a reproducibility analysis. Significant association with known microglia density patterns in the human brain supports the utility of the method to generate reliable glia biomarkers.
“We believe that the characterization, using this technique, of relevant aspects of tissue microstructure during inflammation, in a non-invasive and longitudinal way, can have a huge impact on our understanding of the pathophysiology of many brain conditions and can transform the current diagnostic practice and treatment follow-up strategies for neurodegenerative diseases, ”says Silvia de Santis.
To validate the model, the researchers used an established rat inflammation paradigm based on intracerebral lipopolysaccharide (LPS) administration. In this paradigm, the viability and neurological morphology are preserved, while the activation of microglia (the cells of the brain’s immune system) is induced in the first place, and, in a delayed way, a response of astrocytes.
Researchers at the UMH-CSIC Institute of Neuroscience have developed an innovative strategy to obtain images of the activation of microglia and astrocytes in the gray matter of the brain by diffusion-weighted magnetic resonance imaging (dw-MRI). Credit: IN-CSIC-UMH
This time sequence of cellular events allows glial responses to transiently dissociate from neuronal degeneration, and the signature of reactive microglia is investigated independently of astrogliosis.
To isolate the trace of astrocyte activation, the researchers repeated the experiment by pretreating the animals with an inhibitor that temporarily removes about 90% of the microglia.
Subsequently, using an established paradigm of neuronal damage, they tested whether the model was able to reveal neuroinflammatory “footprints” with and without concomitant neurodegeneration.
“This is critical to demonstrating the usefulness of our approach as a platform for the discovery of biomarkers of inflammatory status in neurodegenerative diseases, where both glia activation and neuronal damage are key actors,” they clarify.
See also
Finally, the researchers used an established demyelination paradigm, based on focal administration of lysolecithin, to show that the biomarkers developed do not reflect tissue alterations that are frequently found in brain disorders.
About this neuroimaging research news
Author: Alda ÓlafssonSource: CSICContact: Alda Ólafsson – CSICImage: Image is accredited to IN-CSIC-UMH
Original search: Open access. “Mapping microglia and astrocyte activation in vivo using diffusion MRI” by Raquel Garcia-Hernández et al. Advances in Science
Summary
Microglia mapping and in vivo astrocyte activation by diffusion magnetic resonance imaging
Although glia is increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders, the methods available for imaging these cells in vivo involve invasive procedures or positron emission tomography radiographs, which provide a resolution and low specificity.
Here, we present a non-invasive diffusion-weighted magnetic resonance imaging (MRI) method for imaging changes in glia morphology.
Using rat models of neuroinflammation, degeneration, and demyelination, we demonstrate that diffusion-weighted MRI carries a fingerprint of microglia and astrocyte activation and that population-specific signatures can be quantified noninvasively.
The method is sensitive to changes in glia morphology and proliferation, providing a quantitative account of neuroinflammation, regardless of the existence of concomitant neuronal loss or demyelinating injury.
We demonstrate the translational value of the approach by showing significant associations between MRI and histological markers of microglia in humans.
This framework has the potential to transform basic and clinical research by clarifying the role of inflammation in health and disease.