Of the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in the United States, as many as 75% sustain a "mild" TBI (MTBI), which means that the injury did not cause prolonged loss of consciousness or post-traumatic amnesia. Despite the apparent mild nature of the initial injury, MTBI can cause long-term or permanent impairments and disabilities in a significant proportion of these patients. These disabilities may include memory problems, reduced speed of thinking, depression, heightened stress/anxiety, sleep disorders and symptoms that resemble post-traumatic stress disorder (PTSD). In addition to these neurological sequelae, there are also physiological consequences of MTBI that can render the person more susceptible to further head injuries or other insults to the brain. It is still not known how to predict who will suffer these longer terms consequences of mild TBI.

The goal of this consortium proposal is to reduce the disabilities caused by MTBI through the joint efforts of clinical and basic scientists. To accomplish this goal, Mission Connect, a multi-institutional organization dedicated to facilitate research to improve outcome from central nervous system injury, has brought together experts from four academic institutions in the Texas Gulf Coast region to concentrate on this research effort. The expertise and cooperation represented in this consortium is in excellent position to address major gaps in knowledge about MTBI. Mission Connect will provide administrative support, interacting with the Department of Defense, working with the institutions to assure fiscal accountability and compliance with research regulations, arranging monthly meetings of investigators, and facilitating external review of research progress.

The investigators, working together, will address major issues in the cause, diagnosis, and treatment of MTBI. One set of investigations in this consortium will be working on developing better ways to diagnose MTBI. The current criteria for determining if a person has a MTBI are the historical finding of an injury to the head plus symptoms and/or signs of a brain injury. Imaging tests, like CT (computer tomography) scanning and MRI (magnetic resonance imaging) scanning, have been used to supplement these clinical signs and symptoms to diagnose TBI. However, patients with MTBI may not have any abnormalities on these tests. To improve the diagnosis of MTBI, the investigators will use state-of-the-art neuroimaging technologies, including an MRI technique called diffusion tensor imaging that identifies damage to the white matter tracts in the brain, and magnetoencephalography to provide more sensitive identification of even small areas of brain injury. The early identification of MTBI, and the differentiation of MTBI from post-traumatic stress disorder, a frequent "mimic" of many of the symptoms of MTBI, would allow earlier, more successful treatment.

Another set of investigations in the consortium will concentrate on developing better experimental models of MTBI, concentrating especially on reproducing the kinds of signs and symptoms that occur in people with MTBI as well as reproducing the imaging findings of MTBI using the same sophisticated MRI imaging technology that will be used in the human studies. Better models will facilitate development of more effective treatment in the laboratory and speed the movement of new treatments from laboratory to clinical evaluation.

A final set of investigations will be working in the laboratory to develop better ways to treat MTBI, both by protecting the brain after injury or by enhancing recovery of the brain function after injury. The investigators will take advantage of the experimental models of MTBI that will be developed by the consortium. One drug study that is planned is a Phase II study of a drug called erythropoietin. This drug is already Food and Drug Administration (FDA)-approved and if found to be safe for patients with MTBI, could be moved quickly into a larger Phase III clinical trial. Some of the other drugs that will be studied in the laboratory are also FDA-approved and could also be quickly moved to clinical trials if successful in the laboratory. Novel treatments are proposed that have yet to be studied in this condition. These include stem-cell transplantation, microstimulation of the brain to speed recovery, and administration of very powerful anti-oxidants using a new, tiny "nanotube" delivery system. Experts in brain imaging will study neural circuits in the brain after MTBI, and how these circuits respond to rehabilitative strategies. All of these studies have promise for improving recovery of brain function in MTBI patients.

The strengths of this proposal include the importance of the topic, the expertise of the investigators, the mixture of experienced TBI researchers with scientists who bring new thinking to this project, and the inclusion of critical stakeholders. All of these efforts will occur within the framework of a functioning organization, ensuring the ability of these investigators to work together across institutions and hospitals.