Rat transcriptome biomarkers for the prediction of temporal lobe epilepsy

用于预测颞叶癫痫的大鼠转录组生物标志物

• 批准号: 7885697
• 负责人: Stanislav Karsten
• 金额: $ 1.5万
• 依托单位: NEUROINDX INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885697
• 关键词: Accounting; Acute; Adolescent; Adult; Age; Animals; Antiepileptic Agents; Antiepileptogenic; Biological Assay; Biological Markers; Blood; Blood Tests; Candidate Disease Gene; Characteristics; Childhood; Chronic; Classification; Commit; Custom; DNA; DNA Microarray Chip; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Effectiveness; Electroencephalography; Electrophysiology (science); Epilepsy; Event; Female; Frequencies; Gender; Gene Expression; Gene Expression Profile; Genes; Genome; Genomics; Goals; Hippocampus (Brain); Individual; Injection of therapeutic agent; Kainic Acid; Laboratories; Lead; Leukocytes; Methods; Modeling; Monitor; Nerve Degeneration; Neurologic; Oligonucleotide Microarrays; Patients; Pattern; Peripheral; Phase; Pilocarpine; Population; Preventive; Procedures; Prophylactic treatment; RNA; Rattus; Reaction; Recurrence; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Seizures; Severities; Specificity; Sprague-Dawley Rats; Status Epilepticus; Susceptibility Gene; Synapses; Syndrome; Technology; Temporal Lobe Epilepsy; Testing; Time; Validation; Variant; Whole Blood; aged; base; clinically relevant; cost; design; functional genomics; male; novel; outcome forecast; peripheral blood; postnatal; prevent; prognostic; response; sex; tool

DESCRIPTION (provided by applicant): Status epilepticus (SE) is a common cause of hippocampal neurodegeneration and synaptic reorganization that ultimately may, or may not lead to the development of temporal lobe epilepsy (TLE). While the role of SE as a possible cause of TLE has been recognized, no effective prognostic tools exist that would reliably predict whether chronic epilepsy would indeed develop in post-SE patients. Hence it is not known whether post- SE patients should undergo antiepileptogenic preventive therapy, and in which case, the effectiveness of such therapy is difficult to assess. The goal of this proposal is to identify novel and prognostic peripheral biomarkers of TLE applying a microarray-based approach for the analysis of expression changes in the blood of rat models of temporal lobe epilepsy. This will be achieved through comparison and identification of genomic changes in peripheral blood of experimental animals that are common despite animal strain, age, sex, and SE model. Male and female Wistar and Sprague-Dawley rats will be subjected to SE induced by either systemic pilocarpine or intrahippocampal kainic acid during either childhood (postnatal day 35) or adulthood (postnatal day 90). Samples of peripheral blood collected one, three and seven days after SE, will undergo genomic assay. After SE, animals will be continuously monitored using both EEG and video for the occurrence, frequency and severity of spontaneous recurrent limbic seizures for a period of six weeks. Seizure syndrome will be retrospectively correlated with the changes in blood genomic profile. If successful, our study would allow a large-scale parallel, cost-effective expression analysis of genes whose expression is altered in a specific fashion prior to the development of TLE. The project will generate a custom TLE prognostic biomarker chip that can be used both to screen and diagnose potential TLE patients, and to prospectively evaluate the effectiveness of antiepileptogenic therapy. Project narrative: by either systemic pilocarpine or intrahippocampal kainic acid is an acute neurological condition that consists of an episode of long-lasting continuous seizure. After SE, significant portion of patients develop chronic epilepsy. Currently no diagnostic tools exist that would allow predicting whether post-SE patient would develop epilepsy. The current project proposes the development of a simple diagnostic blood test method that would allow predicting the development of epilepsy in post-SE patients. The test will be based on the detection of characteristic gene expression changes in the peripheral blood that precede the progression of epilepsy. This will provide an important diagnostic tool and could indicate the necessity of prophylactic treatment to prevent the development and progression of chronic epilepsy. Such a test would also be useful in prognostic assessment of the effectiveness of antiepileptic therapy.

描述（由申请人提供）：状态癫痫症（SE）是海马神经退行性创变和突触重组的常见原因，最终可能或可能不会导致颞叶癫痫（TLE）的发展。尽管已经确认了SE作为TLE的可能原因的作用，但没有有效的预后工具可以可靠地预测SE后患者的慢性癫痫是否确实会发展。因此，尚不清楚后SE患者是否应该接受抗癫痫发作的预防疗法，在这种情况下，这种疗法的有效性很难评估。该提案的目的是确定TLE的新颖和预后的外围生物标志物，采用基于微阵列的方法来分析颞叶癫痫大鼠模型的表达变化。这将通过比较和鉴定实验动物的外周血的基因组变化来实现，尽管动物菌株，年龄，性别和SE模型是常见的。男性和女性Wistar和Sprague-Dawley大鼠将在儿童期（产后第35天）或成年期（第90天）诱导全身性毛car虫或汉皮胶体内海藻酸引起的SE。在SE之后收集了一，三和七天的外周血样本将接受基因组测定。 SE之后，将使用脑电图和视频持续监测动物，以期在六个星期内发生自发反复发作的边缘癫痫发作的发生，频率和严重程度。癫痫发作综合征将回顾性地与血液基因组谱的变化相关。如果成功的话，我们的研究将允许对基因的大规模平行，成本效益的表达分析，其在TLE发展之前以特定方式改变了表达。该项目将产生一种自定义的预后生物标志物芯片，可用于筛查和诊断潜在的TLE患者，并前瞻性评估抗癫痫疗法的有效性。 项目叙述：由全身性毛果氨酸或汉帕克胶内海藻酸是一种急性神经系统疾病，由持续持续癫痫发作的发作组成。 SE之后，大部分患者发生慢性癫痫。目前尚无诊断工具，可以预测SE后患者是否会发展癫痫。当前的项目提出了一种简单的诊断血液测试方法，该方法将允许预测SE后患者癫痫的发展。该测试将基于在癫痫进展之前的外周血中的特征基因表达变化的检测。这将提供一个重要的诊断工具，并可能表明需要预防治疗以防止慢性癫痫的发展和进展。这种测试也将有助于对抗癫痫疗法有效性的预后评估。