Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

Wu, Chunying; Eck, Brendan L.; Zhang, Sheng; Zhu, Junqing; Tiwari, Anand D.; Zhang, Yifan; Zhu, Yunjie; Zhang, Jinming; Wang, Bin; Wang, Xizhen; Wang, Xu; You, Jingqiang; Wang, Jian; Guan, Yihui; Liu, Xingdang; Yu, Xin; Trapp, Bruce D.; Miller, Robert H.; Silver, Jerry; Wilson, David L.; Wang, Yanming

doi:10.1021/acs.jmedchem.6b01328

Cited by 20 publications

(17 citation statements)

References 34 publications

(72 reference statements)

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“…The radiolabeling synthesis of 18 F-FDG and PET-CT scanning was conducted as described previously [ 23 , 25 ]. Before 18 F-FDG injection, mice were fasted overnight with free access to water.…”

Section: Methodsmentioning

confidence: 99%

Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not

et al. 2018

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BackgroundThe underlying mechanism of brain glucose hypometabolism, an invariant neurodegenerative feature that tightly correlates with cognitive impairment and disease progression of Alzheimer’s disease (AD), remains elusive.MethodsPositron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[18F]fluoro-2-deoxy-d-glucose standardized uptake value ratio (FDG SUVR) in patients with AD or control subjects and in mice with or without thiamine deficiency induced by a thiamine-deprived diet. Brain amyloid-β (Aβ) deposition in patients with clinically diagnosed AD was quantified by performing assays using 11C-Pittsburgh compound B PET. The levels of thiamine metabolites in blood samples of patients with AD and control subjects, as well as in blood and brain samples of mice, were detected by high-performance liquid chromatography with fluorescence detection.ResultsFDG SUVRs in frontal, temporal, and parietal cortices of patients with AD were closely correlated with the levels of blood thiamine diphosphate (TDP) and cognitive abilities, but not with brain Aβ deposition. Mice on a thiamine-deprived diet manifested a significant decline of FDG SUVRs in multiple brain regions as compared with those in control mice, with magnitudes highly correlating with both brain and blood TDP levels. There were no significant differences in the changes of FDG SUVRs in observed brain regions between amyloid precursor protein/presenilin-1 and wild-type mice following thiamine deficiency.ConclusionsWe demonstrate, for the first time to our knowledge, in vivo that TDP reduction strongly correlates with brain glucose hypometabolism, whereas amyloid deposition does not. Our study provides new insight into the pathogenesis and therapeutic strategy for AD.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0354-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not

et al. 2018

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“…Additionally, diffusion MRI protocols such as diffusion tensor imaging (DTI) or neurite orientation dispersion and density imaging (NODDI) 13 allow the investigation of microstructural alterations (mainly white matter damage) and discrimination of CSF, extracellular and www.nature.com/scientificreports/ intracellular water. The results obtained with perfusion (DSC-MRI), permeability (DCE-MRI) or diffusion (DTI and NODDI) protocols could be accurately validated with our technique, by means of the co-registration of MRI with high-resolution confocal images obtained upon in vivo labeling of vessels (already explored in this work) 40 .…”

Section: Discussionmentioning

confidence: 73%

Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma

Peviani

Spano

Pagani

et al. 2020

Sci Rep

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In this work we optimized a novel approach for combining in vivo MRI and ex vivo high-resolution fluorescence microscopy that involves: (i) a method for slicing rat brain tissue into sections with the same thickness and spatial orientation as in in vivo MRI, to better correlate in vivo MRI analyses with ex-vivo imaging via scanning confocal microscope and (ii) an improved clearing protocol compatible with lipophilic dyes that highlight the neurovascular network, to obtain high tissue transparency while preserving tissue staining and morphology with no significant tissue shrinkage or expansion. We applied this methodology in two rat models of glioblastoma (GBM; U87 human glioma cells and patient-derived human glioblastoma cancer stem cells) to demonstrate how vital the information retrieved from the correlation between MRI and confocal images is and to highlight how the increased invasiveness of xenografts derived from cancer stem cells may not be clearly detected by standard in vivo MRI approaches. The protocol studied in this work could be implemented in pre-clinical GBM research to further the development and validation of more predictive and translatable MR imaging protocols that can be used as critical diagnostic and prognostic tools. The development of this protocol is part of the quest for more efficacious treatment approaches for this devastating and still uncurable disease. In particular, this approach could be instrumental in validating novel MRI-based techniques to assess cellular infiltration beyond the macroscopic tumor margins and to quantify neo-angiogenesis.

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“…Myelin integrity is an important factor in maintaining the physiological function of the central nervous system. e preservation and regeneration of myelin integrity after SCI plays a key role in the recovery of spinal cord function [18,19]. Acute disturbance of nodal organization after SCI exposes the axon and triggers conduction block in the absence of overt demyelination.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ginkgo biloba on Early Decompression after Spinal Cord Injury

Guo

Wang

Dong³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Spinal cord injury (SCI) is a severe trauma of the central nervous system characterized by high disability and high mortality. Clinical progress has been achieved in understanding the pathological mechanism of SCI and its early treatment, but the results are unsatisfactory. In China, increasing attention has been paid to the role of traditional Chinese medicine in the treatment of SCI. In particular, extracts from the leaves of Ginkgo biloba (maidenhair tree), which have been reported to exert anti-inflammatory and antioxidant properties and repair a variety of active cellular damage, have been applied therapeutically for centuries. In this study, we established a rat SCI model to investigate the effects of Ginkgo biloba leaves on decompression at different stages of SCI. The application of Ginkgo biloba leaves during the decompression of SCI at different time points, the neurological recovery of SCI, and the underlying molecular mechanism were explored. The findings provide reliable experimental data that reveal the mechanism of GBI (Ginkgo biloba injection) in the clinical treatment of SCI.

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Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

Cited by 20 publications

References 34 publications

Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not

Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not

Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma

Effects of Ginkgo biloba on Early Decompression after Spinal Cord Injury

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