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以三酰甘油作为潜在生物标志物的病理学特异性脂质改变在局灶性皮质发育不良(FCD)和伴海马硬化的内侧颞叶癫痫(MTLE-HS)中的研究

Pathology-specific lipid alterations with triacylglycerol as a potential biomarker in Focal cortical dysplasia (FCD) and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS).

作者信息

Yadav Nitin, Anand Sneha, Kumar Krishan, Doddamani Ramesh, Tripathi Manjari, Chandra P Sarat, Lalwani Sanjeev, Sharma M C, Banerjee Jyotirmoy, Dixit Aparna Banerjee

机构信息

Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India; Department of Biomedical Science, Bhaskaracharya College of Applied Sciences, University of Delhi, Delhi, India.

Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India; Department of Acute Brain Damage & Cardiovascular Research, Mario Negri Institute of Pharmacological Research, Milan, Italy.

出版信息

Neuroscience. 2025 Feb 6;566:72-86. doi: 10.1016/j.neuroscience.2024.12.038. Epub 2024 Dec 21.

Abstract

Focal Cortical Dysplasia (FCD) & Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) are two common pathologies of drug-resistant focal epilepsy (DRE). Inappropriate localization of the epileptogenic zones (EZs) in FCD is a significant contributing factor to the unsatisfactory surgical results observed in FCD cases. Currently, no molecular or cellular indicators are available which can aid in identifying the epileptogenic zones (EZs) in FCD. Phospholipid modifications in healthy and malignant tumour tissues have been documented and used to demarcate tumour boundaries. The objective of this research was to analyze and evaluate the lipid profiles in a manner that takes into account the specific disease and subtype. The technique of liquid chromatography and tandem mass spectrometry was utilized to detect changes in lipids in surgically resected brain samples from patients with FCD and MTLE-HS, in comparison to non-epileptic controls. Significant upregulation of TAGs was seen in both FCD and MTLE-HS. Additionally, the levels of triglycerides in the plasma of peripheral blood were measured in patients with FCD, MTLE-HS, and healthy individuals as controls. These findings suggest that employing distinct lipid mass spectra could be an effective method for identifying the EZs in FCD. The unique lipid mass spectra of cortical tissues from patients with FCD can be utilized for real-time surgical guidance. Additionally, the plasma triglyceride (TAG) level has the potential to act as a biomarker once validated on a larger cohort.

摘要

局灶性皮质发育不良(FCD)和内侧颞叶癫痫-海马硬化(MTLE-HS)是药物难治性局灶性癫痫(DRE)的两种常见病理类型。FCD中致痫区(EZs)定位不当是FCD病例手术效果不理想的一个重要因素。目前,尚无分子或细胞指标可用于识别FCD中的致痫区(EZs)。健康和恶性肿瘤组织中的磷脂修饰已有记录,并用于划定肿瘤边界。本研究的目的是以考虑特定疾病和亚型的方式分析和评估脂质谱。利用液相色谱和串联质谱技术检测FCD和MTLE-HS患者手术切除的脑样本与非癫痫对照相比脂质的变化。在FCD和MTLE-HS中均观察到TAGs显著上调。此外,还测量了FCD、MTLE-HS患者以及作为对照的健康个体外周血血浆中的甘油三酯水平。这些发现表明,采用独特的脂质质谱可能是识别FCD中致痫区的有效方法。FCD患者皮质组织独特的脂质质谱可用于实时手术指导。此外,血浆甘油三酯(TAG)水平一旦在更大的队列中得到验证,有可能作为一种生物标志物。

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