microRNA Profiling to Characterize and Predict Posttraumatic Epilepsy Following Traumatic Brain Injury
Abstract
Traumatic brain injury (TBI) is the leading cause of death and disability worldwide, and the economic cost is expected to reach $80 billion in the United States. TBI is a complex condition resulting from a variety of civilian and military causes. Whereas vehicle accidents are the predominant cause in the general population, blast injuries are the major cause of severe TBI among Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) military personnel. Beyond the primary injuries, TBI can lead to multiple secondary problems, including posttraumatic epilepsy (PTE), which can develop weeks to years after the initial injury. Severe TBI is a strong risk factor for development of epilepsy. The severity of injury, including duration of amnesia, presence of bleeding in the brain, and skull fracture are used clinically as risk factors to determine the likelihood of a patient developing PTE. However, the certainty of developing or not developing PTE based on risk factors alone is very limited. Clinicians and patients are forced to make decisions about the need for PTE treatment based on this very limited information. In this proposal, we seek to discover molecular signals in blood from TBI patients that can improve diagnosis and prediction for PTE. We will investigate whole blood from TBI patients and determine the different patterns of a specific group of molecules called microRNA (or miRNA). miRNAs are important for regulating the expression of specific genes. The pattern of miRNA expression is changed by many factors, including after a TBI or in patients with epilepsy. We will determine the pattern of miRNAs that are present in patients with TBI but without epilepsy, and those with TBI + epilepsy. We will also track blood miRNA patterns over time following injury to determine if a specific change can be detected that will indicate whether a TBI patient is at low or high risk for going on to develop epilepsy. We hypothesize that expression patterns of miRNA in blood, combined with clinical information, will allow for distinguishing between TBI patients with and without epilepsy. We further hypothesize that miRNA profiling of whole blood can reveal molecular changes underlying epilepsy development and can identify certain molecular patterns that predict epilepsy following TBI. The ultimate goal is a simple blood test based on a combined molecular and clinical algorithm that will help stratify patients with similar TBI presentation the need for prophylactic antiepileptic drug (AED) treatment and for long-term AED treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810246
Entities
People
- Timothy Veldman
Organizations
- Duke University
- United States Army