Imaging epileptic foci in mouse models via a low-density lipoprotein receptor-related protein-1 targeting strategy

Zhang, Jianping; Song, Shaoli; Li, Zhi; Yin, Shujie; Duan, Wenjia; Wei, Zixuan; Qi, Ming; Sun, Wen; Zhang, Lu; Luo, Chen; Gao, Xihui; Mao, Ying; Wang, Hao; Chen, Liang; Liu, Cong

doi:10.1016/j.ebiom.2020.103156

Cited by 11 publications

(18 citation statements)

References 37 publications

(38 reference statements)

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Section: Il-1βmentioning

confidence: 99%

“…Reduced LRP1 levels have been observed to drastically decrease Tau protein uptake and diffusion in neurons, [123] while LRP1 expression is upregulated in inflammation, tissue damage, and repair areas. Wang et al [124] found LRP1 expression was upregulated in vascular endothelial cells, activated astrocytes, and microglia in both epileptic patients and mouse models. The immunofluorescence results showed that LRP1 expression levels in the EF of DRE patients were about two fold than that in control brain tissues.…”

Section: Probes For Imaging Inflammation-related Receptorsmentioning

confidence: 99%

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confidence: 99%

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Tailoring Materials for Epilepsy Imaging: From Biomarkers to Imaging Probes

Zhao

Sun

2022

Advanced Materials

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Epilepsy is a recurrent, episodic, and complex neurological syndrome characterized by an enduring predisposition to epileptic seizures and consequent neurological, cognitive, psychological, and social problems. [1] An epileptic seizure is a transient occurrence of symptoms (such as temporary confusion, staring spells, uncontrollable jerking, and loss of awareness) caused by abnormal neuronal electrical activities. [2] As a serious health problem, epilepsy affects ≈1% of the global population, [3] and nearly 5 million people worldwide are diagnosed with epilepsy every year. Although there are now more than 20 antiseizure medications (ASMs) in active clinical use, [4] ≈20-30% of epilepsy patients fail to achieve sustained seizure freedom after adequate trial of two appropriately chosen ASMs. [5] These drugresistant epilepsy (DRE) patients are at an increased risk of injury and death, [6] unbearable medication burden and adverse effects, increased psychiatric and neurocognitive comorbidities, [7] and socioeconomic disadvantage. Therefore, the management of DRE in the clinic is a major challenge.Resection of the epileptic foci (EF), defined as the minimum area of the brain tissue that must be resected or disconnected for the abolishment of seizures, [8] is the most efficient approach for the treatment of DRE patients. [9] First, epilepsy surgery increases the prospects of patients being seizure-free. [10] Approximately 52% of the patients have no disabling seizures for 5 years after surgery, and nearly half of the patients remain free from seizures for 10 years. [11] Second, surgical treatment reduces DRE patients' mortality by two to three times [12] and extends life expectancy by an average of 5 years in comparison to patients who have received drug therapy. [13] Third, epilepsy surgery reduces individual medical expenditures for families. [14] Overall, these results suggest that DRE is potentially curable with surgical intervention. Accurate identification of the EF is a prerequisite for achieving satisfactory postsurgical outcomes. [15] However, only a small percentage of patients is recommended for surgical treatment because of the difficulty in defining EF. First, an initial clinical assessment, including history of epilepsy, semiology information, drug history, and comorbidity, will be performed in the clinic to confirm whether the patients are suitable for surgery. Next, high-resolution structural magnetic resonance imaging (MRI) and long-term inpatient video electroencephalography (EEG) are conducted. [16] If MRI shows Excising epileptic foci (EF) is the most efficient approach for treating drugresistant epilepsy (DRE). However, owing to the vast heterogeneity of epilepsies, EF in one-third of patients cannot be accurately located, even after exhausting all current diagnostic strategies. Therefore, identifying biomarkers that truly represent the status of epilepsy and fabricating probes with high targeting specificity are prerequisites for identifying the "concealed" EF. However, no systematic summary of thi...

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Section: Il-1βmentioning

confidence: 99%

Section: Probes For Imaging Inflammation-related Receptorsmentioning

confidence: 99%

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Tailoring Materials for Epilepsy Imaging: From Biomarkers to Imaging Probes

Zhao

Sun

2022

Advanced Materials

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“…14 An increase in LRP1 expression in the brain tissue resected from DRE patients and epileptic mice has been reported in our previous work; thus, it can be used as a biomarker to locate epileptic lesions. 15 A variety of imaging methods have been used for preoperative evaluations of DRE patients. 5 Among these, single-photon emission computed tomography (SPECT) is a powerful preoperative imaging technology for its satisfactory penetration depth and sensitivity, thus improving the accuracy of diagnosis by obtaining the anatomic and metabolic information at the same time, which is superior to structural MRI in the detection of subtle underlying lesions.…”

Section: ■ Introductionmentioning

confidence: 99%

Guiding Epilepsy Surgery with an LRP1-Targeted SPECT/SERRS Dual-Mode Imaging Probe

Sun

Duan

et al. 2022

ACS Appl. Mater. Interfaces

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Accurate identification of the resectable epileptic lesion is a precondition of operative intervention to drug-resistant epilepsy (DRE) patients. However, even when multiple diagnostic modalities are combined, epileptic foci cannot be accurately identified in ∼30% of DRE patients. Inflammation-associated low-density lipoprotein receptor-related protein-1 (LRP1) has been validated to be a surrogate target for imaging epileptic foci. Here, we reported an LRP1-targeted dual-mode probe that is capable of providing comprehensive epilepsy information preoperatively with SPECT imaging while intraoperatively delineating epileptic margins in a sensitive high-contrast manner with surface-enhanced resonance Raman scattering (SERRS) imaging. Notably, a novel and universal strategy for constructing self-assembled monolayer (SAM)-based Raman reporters was proposed for boosting the sensitivity, stability, reproducibility, and quantifiability of the SERRS signal. The probe showed high efficacy to penetrate the blood–brain barrier. SPECT imaging showed the probe could delineate the epileptic foci clearly with a high target-to-background ratio (4.11 ± 0.71, 2 h). Further, with the assistance of the probe, attenuated seizure frequency in the epileptic mouse models was achieved by using SPECT together with Raman images before and during operation, respectively. Overall, this work highlights a new strategy to develop a SPECT/SERRS dual-mode probe for comprehensive epilepsy surgery that can overcome the brain shift by the co-registration of preoperative SPECT and SERRS intraoperative images.

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“…In this article of EBioMedicine [1], Li and colleagues developed a micellar-based lipoprotein receptor-related protein-1 (LRP1)-targeting T 1 MRI contrast agent as a novel approach to map the epileptic foci. Their work showed that although the blood brain barrier (BBB) in the epileptic region of drug-resistant epileptic (DRE) patients and kainate mouse models were mostly intact, there was a notable increase in the expression of LRP1.…”

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confidence: 99%