Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor

  title={Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor},
  author={Jun Maeda and Makoto Higuchi and Motoki Inaji and Bin Ji and Eisuke Haneda and Takashi Okauchi and Ming-Rong Zhang and Kazutoshi Suzuki and Tetsuya Suhara},
  journal={Brain Research},
Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies
Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD.
Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain
The first comprehensive immunohistochemical analysis of the expression of TSPO is provided, useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of T SPO as an anti‐inflammatory pharmacological target.
Spatiotemporal Distribution of Microglia After Traumatic Brain Injury in Male Mice
A controlled cortical impact injury model was used to quantify and characterize microglia at 24 hr and 28 days after TBI in the hippocampus (H) and lateral posterior nucleus of the thalamus (LPNT), and results in a spatiotemporal increase in amoeboid microglial increases in both H and LPNT over 28 days.
Regional sensitivity to neuroinflammation: In vivo and in vitro studies
The results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component.
Roles of microglia in brain development, tissue maintenance and repair.
Molecular signatures of myeloid cells are identified, suggesting that microglia are a distinct cell population compared to other cells ofmyeloid lineage that access the central nervous system under pathological conditions.
Molecular imaging of microglia/macrophages in the brain
An overview of positron emission tomography (PET) and magnetic resonance (MR) imaging of microglia/macrophages in the brain and the potential of PET imaging agents for targets other than TSPO are outlined.
Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging
It is shown that reactive astrocytes overexpress TSPO, yielding to a significant and selective binding of T SPO radioligands, which means that caution must be used when interpreting TSPo PET imaging in animals or patients because reactive ast rocytes can contribute to the signal in addition to reactive microglia.
Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial Activation in the Mouse Retina
The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence.
The role of the microglia in acute CNS injury
An overview of the recent progress relating on the deleterious and beneficial effect of microglia in the setting of acute CNS injury and the potential therapeutic intervention against microglial activation to CNS injury is provided.


Peripheral benzodiazepine receptors are colocalized with activated microglia following transient global forebrain ischemia in the rat
The data strongly suggest that activated microglia rather than astrocytes express PBRs following ischemic insults, and lend further support to the application of 3H-PK11195 binding as a marker of neuronal injury in the brain.
Cellular and Subcellular Localization of Peripheral Benzodiazepine Receptors After Trimethyltin Neurotoxicity
It is demonstrated that PBR expression is increased after brain injury in both activated microglia and astrocytes, and the first evidence for in situ nuclear localization of PBR in glial cells is provided.
Traumatic Brain Injury Leads to Increased Expression of Peripheral-Type Benzodiazepine Receptors, Neuronal Death, and Activation of Astrocytes and Microglia in Rat Thalamus
Increased PTBR expression following TBI seems to be associated with microglia/macrophages than astrocytes as PTBR density at different periods after TBI correlated better with the number of ED-1 positive cells than the GFAP positive cells.
Ro5‐4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity
The findings suggest that the PBR is involved in control of neuronal survival and gliosis after brain injury and identify this molecule as a potential target for neuroprotective interventions.
Imaging the peripheral benzodiazepine receptor response in central nervous system demyelination and remyelination.
  • Ming-Kai Chen, T. Guilarte
  • Biology, Psychology
    Toxicological sciences : an official journal of the Society of Toxicology
  • 2006
The results indicate that 11C-(R)-PK11195 levels are significantly elevated in the mouse brain during cuprizone-induced demyelination and normalize at a time in which remyelinations is complete, supporting the notion that PBR is a sensitive marker for the visualization and quantification of brain injury and recovery.
The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.
This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology.
Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury
It is suggested that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.
Macrophage colony‐stimulating factor is expressed in neuron and microglia after focal brain injury
The results suggest that neurons around the damaged area express M‐CSF in the early phase after injury, and these activated microglia also express M-CSF later, causing further proliferation or migration ofmicroglia themselves to eliminate damaged neurons or necrotic brain tissue.
Axonal injury‐dependent induction of the peripheral benzodiazepine receptor in small‐diameter adult rat primary sensory neurons
The peripheral benzodiazepine receptor (PBR), a benzodiazepine but not γ‐aminobutyric acid‐binding mitochondrial membrane protein, has roles in steroid production, energy metabolism, cell survival