exRNA signatures Predict Outcomes after brain injury

exRNA 特征预测脑损伤后的结果

• 批准号: 9128756
• 负责人: P. David ADELSON
• 金额: $ 94.9万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9128756
• 关键词: Adult; Aneurysmal Subarachnoid Hemorrhages; Biological Assay; Biological Markers; Blood; Brain; Brain Injuries; Caring; Cerebrospinal Fluid; Chemistry; Childhood; Clinical; Clinical assessments; Collaborations; Collection; Creation of ventriculo-peritoneal shunt; Data; Data Collection; Detection; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnostic; Disease Outcome; Enrollment; Event; Excision; Exhibits; Grant; Health; Healthcare Systems; Hemorrhage; Hydrocephalus; Image; Infarction; Injury; Institutes; Lead; Medical Records; MicroRNAs; Monitor; Morbidity - disease rate; Multivariate Analysis; Neurologic; Neurological outcome; Outcome; Pathway interactions; Patient risk; Patient-Focused Outcomes; Patients; Performance; Phase; Plasma; Population; Premature Infant; Process; Prognostic Marker; RNA; RNA marker; Research; Running; Rupture; Sampling; Sensitivity and Specificity; Sequence Analysis; Severities; Severity of illness; Shunt Device; Signal Transduction; Small RNA; Source; Techniques; Testing; Time; Trauma; Traumatic Brain Injury; Validation; Vasospasm; Ventricular; Visit; biomarker discovery; biomarker identification; candidate marker; cost; differential expression; extracellular; follow-up; improved; infant outcome; innovation; intraventricular hemorrhage; microRNA biomarkers; microvesicles; mortality; new technology; next generation sequencing; novel therapeutic intervention; potential biomarker; predictive marker; research clinical testing; sample collection; transcriptome; treatment strategy

DESCRIPTION (provided by applicant): Traumatic brain injury, both from direct trauma to the brain and as a sequela of ischemic or hemorrhagic infarction are associated with a significant rate of morbidity, mortality and cost to both patients and the healthcare system. Hemorrhagic infarcts (such as aneurysmal subarachnoid hemorrhage and intraventricular hemorrhage) are rare but devastating complications of arterial rupture. Despite significant effort, there has been little improvement in the outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) or intraventricular hemorrhage (IVH). Given the predictable temporal course of these brain injuries, they are ideal candidates for biomarker identification. A biomarker for detection o 'at risk' patients and a prognostic indicator of delayed neurological deficit would vastly improve current treatments and increase our understanding of underlying pathological events. This information would immediately lead to the implementation of new therapeutic strategies. Research over the last several years has identified extracellular RNAs (exRNA) as a potential source of biomarkers. New technology, such as next generation sequencing (NGS), has made it possible to sensitively and quantitatively assay small amounts of RNA contained in clinically attainable volumes of biofluids such as CSF and blood plasma. In the first two years of this grant, we propose to sequene the exRNA (miRNA and total RNA) from both the CSF and plasma of patients who present with aSAH and the plasma and CSF from premature infants born with IVH. aSAH samples were collected daily~ the volume of sample available will allow us not only to sequence the total RNA including miRNAs, but will permit us to explore unique enrichment strategies in years 3-5 of this grant~ we will examine specific RNAs associated with microvesicles in both CSF and plasma. We have both the daily clinical evaluations of these patients as well as their outcomes (25 subjects in all). We will use these samples to identiy RNA markers that predict onset of vasospasm and the severity of delayed neurological deficits. We also have CSF and plasma samples collected every other day from premature infants with grade III-IV IVH that had reservoirs put in place to evacuate blood and excess CSF. We also have the clinical outcomes from the infants, whether or not they developed hydrocephalus, the need for a permanent shunt, and an 18 month assessment of developmental delays or disabilities. In years 3-5, we will continue to collect samples in collaboration with both of our clinical partners. At that time, we will switch from our discovery platform, the Illumina HiSeq 2000 that has high depth of sequencing coverage, to the Illumina MiSeq for validation. Once the discovery phase is complete and potential biomarkers identified, validation can be carried out on the MiSeq's faster fluidics, imaging, and shortened run times without changing chemistries between the discovery and validation phases.

描述（由申请人提供）：