Changes in Binding of [123I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury

Donat, Cornelius K.; Gaber, Khaled R.; Meixensberger, Jürgen; Brust, Peter; Pinborg, Lars H.; Hansen, Henrik H.; Mikkelsen, Jens D.

doi:10.1007/s12017-016-8385-y

Cited by 20 publications

(24 citation statements)

References 66 publications

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“…Information on the elevation of TSPO would be useful in detecting tumorigenicity of the transplanted hiPSC‐NS/PCs by carefully selecting when to perform the PET scan. For example, there is a dramatic increase in inflammation and associated activation of TSPO‐expressing microglia after TBI or SCI . Moreover, it has been reported that the activated Iba1 + microglia, which present a major cellular source of TSPO, peaks 42 days post‐SCI while TSPO expression peaks within a week or 72 hours after infarction, especially in the cerebral infarction models and the brain injury models, respectively .…”

Section: Discussionmentioning

confidence: 99%

“…For example, there is a dramatic increase in inflammation and associated activation of TSPO‐expressing microglia after TBI or SCI . Moreover, it has been reported that the activated Iba1 + microglia, which present a major cellular source of TSPO, peaks 42 days post‐SCI while TSPO expression peaks within a week or 72 hours after infarction, especially in the cerebral infarction models and the brain injury models, respectively . In order to elucidate time‐dependent changes of TSPO expression after SCI in rodent models, we analyzed the gene expression of TSPO in mice at the nine days marker and 42 days marker after SCI using microarray.…”

Section: Discussionmentioning

confidence: 99%

“…55 In clinical application of patients with chronic TBI or SCI, we believe selection of the timing of the PET scan is essential in diagnos- 33,56 Moreover, it has been reported that the activated Iba1 + microglia, which present a major cellular source of TSPO, peaks 42 days post-SCI 50 while TSPO expression peaks within a week or 72 hours after infarction, especially in the cerebral infarction models and the brain injury models, respectively. 56,57 In order to elucidate time-dependent changes of TSPO expression after SCI in rodent models, we analyzed the gene expression of TSPO in mice at the nine days marker and 42 days marker after SCI using microarray. We observed that TSPO was significantly elevated 9 days after injury (dpi) ( Figure S7) and there was no significant difference between 9 and 42 dpi.…”

Section: [ 18 F] Fedacmentioning

confidence: 99%

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In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Tanimoto

Yamasaki

Nagoshi

et al. 2020

Stem Cells Translational Medicine

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Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: [ 18 F] Fedacmentioning

confidence: 99%

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In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Tanimoto

Yamasaki

Nagoshi

et al. 2020

Stem Cells Translational Medicine

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“…Research concerning TSPO ligand uptake in animal models of TBI overwhelmingly supports the findings of its role as a microglia/macrophage activator. Specifically, studies have revealed that the increases of BP using 11C-PK11195 can be associated with both the time and type of brain injury [174][175][176]. Investigations using second-generation ligands fully support the results of the increased uptake in different types of trauma but are in contrast with the findings of increases of TSPO expression early after traumatic events [50].…”

Section: Tspo and Traumatic Brain Injuries (Tbis)mentioning

confidence: 96%

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

Dimitrova-Shumkovska

Krstanoski

Veenman

2020

Cells

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Neuroinflammation and cell death are among the common symptoms of many central nervous system diseases and injuries. Neuroinflammation and programmed cell death of the various cell types in the brain appear to be part of these disorders, and characteristic for each cell type, including neurons and glia cells. Concerning the effects of 18-kDa translocator protein (TSPO) on glial activation, as well as being associated with neuronal cell death, as a response mechanism to oxidative stress, the changes of its expression assayed with the aid of TSPO-specific positron emission tomography (PET) tracers’ uptake could also offer evidence for following the pathogenesis of these disorders. This could potentially increase the number of diagnostic tests to accurately establish the stadium and development of the disease in question. Nonetheless, the differences in results regarding TSPO PET signals of first and second generations of tracers measured in patients with neurological disorders versus healthy controls indicate that we still have to understand more regarding TSPO characteristics. Expanding on investigations regarding the neuroprotective and healing effects of TSPO ligands could also contribute to a better understanding of the therapeutic potential of TSPO activity for brain damage due to brain injury and disease. Studies so far have directed attention to the effects on neurons and glia, and processes, such as death, inflammation, and regeneration. It is definitely worthwhile to drive such studies forward. From recent research it also appears that TSPO ligands, such as PK11195, Etifoxine, Emapunil, and 2-Cl-MGV-1, demonstrate the potential of targeting TSPO for treatments of brain diseases and disorders.

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“…While the primary injury is the initial biomechanical trauma [ 50 ], a process involving neuronal, axonal and vascular damage induced by the kinetic energy, this induces a cascade of secondary processes leading to excitotoxicity, necrosis, apoptosis, autophagy and free radical formation [ 51 ]. Hence, TBI is considered to be a chronic disease [ 52 ], implicating that the pathophysiological and inflammatory processes in the brain take place at different times after the injury, where some are beneficial to recovery and others are generated by the injury and exaggerate the primary damage [ 53 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

PET Evaluation of Microglial Activation in Non-neurodegenerative Brain Diseases

Ghadery

Best

Pavese

et al. 2019

Curr Neurol Neurosci Rep

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Purpose of the Review Microglial cell activation is an important component of neuroinflammation, and it is generally well accepted that chronic microglial activation is indicative of accumulating tissue damage in neurodegenerative conditions, particularly in the earlier stages of disease. Until recently, there has been less focus on the role of neuroinflammation in other forms of neurological and neuropsychiatric conditions. Through this review, we hope to demonstrate the important role TSPO PET imaging has played in illuminating the pivotal role of neuroinflammation and microglial activation underpinning these conditions. Recent Findings TSPO is an 18 kDa protein found on the outer membrane of mitochondria and can act as a marker of microglial activation using nuclear imaging. Through the development of radiopharmaceuticals targeting TSPO, researchers have been able to better characterise the spatial-temporal evolution of chronic neurological conditions, ranging from the focal autoimmune reactions seen in multiple sclerosis to the Wallerian degeneration at remote parts of the brain months following acute cerebral infarction. Summary Development of novel techniques to investigate neuroinflammation within the central nervous system, for the purposes of diagnosis and therapeutics, has flourished over the past few decades. TSPO has proven itself a robust and sensitive biomarker of microglial activation and neuroimaging affords a minimally invasive technique to characterise neuroinflammatory processes in vivo.

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Changes in Binding of [123I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury

Cited by 20 publications

References 66 publications

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

PET Evaluation of Microglial Activation in Non-neurodegenerative Brain Diseases

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