Visualising microglial activation in vivo
Open accessAbstract
In health, microglia reside as quiescent guardian cells ubiquitously, but isolated without any cell‐cell contacts amongst themselves, throughout the normal CNS. In disease, however, they act as swift “sensors” for pathological events, including subtle ones without any obvious structural damage. Once activated, microglia show a territorially highly restricted involvement in the disease process. This property, peculiar to microglia, confers to them diagnostic value for the accurate spatial localisation of any active disease process, acute or chronic. In the brain, the isoquinoline PK11195, a ligand for the peripheral benzodiazepine binding site (PBBS), binds with relative cellular selectivity to activated, but not resting, microglia. Labelled with carbon‐11, (R)‐PK11195 and positron emission tomography (PET) have been used for the study of inflammatory and neurodegenerative brain disease in vivo. These studies demonstrate meaningfully distributed patterns of regional [11 C](R)‐PK11195 signal increases that correlate with clinically observed loss of function. Increased [11 C](R)‐PK11195 binding closely mirrors the histologically well‐described activation of microglia in the penumbra of focal lesions, as well as in the distant, anterograde, and retrograde projection areas of the lesioned neural pathway. There is also some indication that in long‐standing alterations of a neural network with persistent abnormal input, additional signals of glial activation may also emerge in transsynaptic areas. These data suggest that the injured brain is less static than commonly thought and shows subtle glial responses even in macroanatomically stable appearing regions. This implies that glial activation is not solely a sign of tissue destruction, but possibly of disease‐induced adaptation or plasticity as well. Whilst further technological and methodological advances are necessary to achieve routine clinical value and feasibility, a systematic attempt to image glial cells in vivo is likely to furnish valuable information on the cellular pathology of CNS diseases and their progression within the distributed neural architecture of the brain. GLIA 40:206–217, 2002. © 2002 Wiley‐Liss, Inc.
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11C-PK-11195 has demonstrated selectivity for activated microglia over quiescent microglia and reactive astrocytes, relative insensitivity to common polymorphisms in TSPO compared to second generation TSPO ligands, and well established methods of non-invasive kinetic analysis.
“However, in favour of the use of 11C-PK-11195 is its demonstrated selectivity for activated microglia over quiescent microglia and reactive astrocytes (Banati, 2002), its relative insensitivity to common polymorphisms in TSPO compared to second generation TSPO ligands (Zhang, 2015; Stefaniak and O’Brien, 2016), and the fact that it has well established methods of non-invasive kinetic analysis (”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Banati, 2002
[11C]PK11195 is selective for activated microglia over quiescent microglia or reactive astrocytes, but has low signal-to-noise ratio and low brain penetration.
“The [11C]PK11195 ligand is selective for activated microglia over quiescent microglia or reactive astrocytes38, but, it has been criticised for its relatively low signal-to-noise ratio and low brain penetration which may affect its sensitivity to activated microglia.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [38]
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- Authors
- Banati, R. B.
- Affiliations
- Hammersmith Hospital (GB)
- Corresponding author
- Banati, Richard B.
- ORCID
- Banati, Richard B.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2002-10-04
- Volume
- 40
- Issue
- 2
- Pages
- 206-217
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2049703902
- Cited by
- 428
- References
- 3
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 13 · 2022: 6 · 2021: 17 · 2020: 23 · 2019: 13 · 2018: 29 · 2017: 22 · 2016: 23 · 2015: 25 · 2014: 30 · 2013: 16 · 2012: 31
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- Deutsche Forschungsgemeinschaft
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- microglial activation, PK11195, neuroinflammation, neurodegenerative diseases, brain injury, penumbra, neuroplasticity
- MeSH terms
- Animals, Binding Sites, Brain Diseases, Carbon Radioisotopes, Encephalitis, Humans, Isoquinolines, Ligands, Magnetic Resonance Imaging, Mitochondria, Predictive Value of Tests, Receptors, GABA-A, Tomography, Emission-Computed, Microglia
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