Dataset Information

Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near-Infrared Fluorescent Probe.

ABSTRACT: Epilepsy is a chronic neurodegenerative disease, and accumulating evidence suggests its pathological progression is closely associated with peroxynitrite (ONOO^-). However, understanding the function remains challenging due to a lack of in vivo imaging probes for ONOO^- determination in epileptic brains. Here, the first near-infrared imaging probe (named ONP) is presented for tracking endogenous ONOO^- in brains of kainate-induced epileptic seizures with high sensitivity and selectivity. Using this probe, the dynamic changes of endogenous ONOO^- fluxes in epileptic brains are effectively monitored with excellent temporal and spatial resolution. In vivo visualization and in situ imaging of hippocampal regions clearly reveal that a higher concentration of ONOO^- in the epileptic brains associates with severe neuronal damage and epileptogenesis; curcumin administration can eliminate excessively increased ONOO^-, further effectively protecting neuronal cells. Moreover, by combining high-content analysis and ONP, a high-throughput screening method for antiepileptic inhibitors is constructed, which provides a rapid imaging/screening approach for understanding epilepsy pathology and accelerating antiseizure therapeutic discovery.

SUBMITTER: Hu JS

PROVIDER: S-EPMC6685465 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near-Infrared Fluorescent Probe.

Hu Jiong-Sheng JS Shao Chenwen C Wang Xueao X Di Xiaojiao X Xue Xuling X Su Zhi Z Zhao Jing J Zhu Hai-Liang HL Liu Hong-Ke HK Qian Yong Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190611 15

Epilepsy is a chronic neurodegenerative disease, and accumulating evidence suggests its pathological progression is closely associated with peroxynitrite (ONOO-). However, understanding the function remains challenging due to a lack of in vivo imaging probes for ONOO- determination in epileptic brains. Here, the first near-infrared imaging probe (named ONP) is presented for tracking endogenous ONOO- in brains of kainate-induced epileptic seizures with high sensit ...[more]

PMID: 31406668

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Project description:BACKGROUND:To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS:The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96?h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS:In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS:COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Dataset Information

Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near-Infrared Fluorescent Probe.

Publications

Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near-Infrared Fluorescent Probe.

Similar Datasets

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