Trauma-Induced Coagulopathy and the Blood-Brain Barrier: Impact of Resuscitation
Abstract
Overall Program: Trauma-Induced Coagulopathy and the Blood-Brain Barrier: Impact of Resuscitation Hemorrhagic shock (HS), or blood loss resulting in decreased blood circulation in the body and, therefore, decreased delivery of blood to tissues and organs, amplifies bleeding and brain function in traumatic brain injury (TBI). The effects of HS are further worsened by trauma-induced fibrinolysis, or increased blood clotting due to traumatic injury. The overarching challenge this proposal addresses is that the mechanisms of HS-induced worsening of TBI are poorly understood. While treatment of HS has been widely studied and well-described, how best to treat TBI in combination with HS is unknown. This is a critical knowledge gap, given that TBI is expected to represent an increasing portion of potentially survivable battlefield injuries in the future. The four projects that comprise our Focused Program Award address Focus Area 2 (Prevent and Assess) and subarea 2a, Identification and validation of biomarkers or other objective markers for diagnosis, prognosis, or monitoring of …TBI and Focus Area 3 (Treat) and subarea 3a, Interventions that promote sustained functional recovery, including interventions administered acutely, during the post-acute phase, or during the chronic phase of injury. We hypothesize that fibrinolysis, the breakdown of blood clots, and platelet dysfunction play a role in blood-brain barrier disruption during TBI that leads to cerebral edema, or brain swelling. We seek to understand these mechanisms using several different strategies, including analyzing blood samples and clinical data from patients with TBI and/or HS, imaging from TBI patients, animal models of TBI and HS, and a novel, dynamic model of the blood-brain barrier. We further seek to identify transfusion practices that not only treat TBI but also minimize complications of traumatic injury. We will accomplish these goals in 4 individual projects which examine the interaction of TBI and HS. We will obtain blood samples from 100 patients admitted to the Shock Trauma Intensive Care Unit at Memorial Hermann-Texas Medical Center, the busiest Level 1 trauma center in the U.S. Patients will be classified as having TBI and/or HS using clinical, laboratory, and imaging information. Additionally, clinical data and follow-up images will be obtained. Projects 1 and 3 will analyze the patient samples to better understand excessive breakdown of blood clots (Project 1) and platelet dysfunction (Project 3). Project 4 will use the laboratory data from Projects 1 and 2, combined with imaging data obtained in Project 4, to quantify and compare brain swelling among 3 patient groups: TBI, TBI+HS, and patients with multiple injuries including TBI but without HS. Project 4 will test critical elements of treatments that influence cerebral edema development and optimize the approach to these patients using data derived from laboratory and animal experiments. We will also employ a Community-based Participatory Research (CBPR) initiative to engage stakeholders in the TBI community as partners in our Program, understanding the issues of a clinical study (risk and its mitigation, informed consent in vulnerable populations, outcome measures) and its impact, as well as addressing barriers to execution of the clinical study (access, enrollment, follow-up). This CBPR approach will not only improve access, enrollment, and execution of our study, as well as generalizability of results by incorporating historically underrepresented minorities in the treatment population, but it will also provide a resource for other investigators pursuing clinical studies in TBI and neurological injuries in terms of research design and pragmatic implications of components of a clinical study from the patient perspective. Findings from this project would provide new information about secondary injury of TBI due to HS, as well as potential therapeutic targets that could
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311033
Entities
People
- C. E. Cox
Organizations
- United States Army
- University of Texas Health Science Center at Houston