Traumatic Brain Injury (TBI): Research Activities and Scientific Advances

TBI can cause short- and long-term physical, cognitive, and emotional problems and is a leading cause of death and disability in children and adults. Understanding the full spectrum of TBI, its short- and long-term effects, and ways to treat or minimize those effects is an active area of research for the NICHD.

Institute Activities and Advances

The NICHD portfolio includes research to understand the mechanisms of TBI, improve prevention and diagnosis of TBI, evaluate treatments for TBI patients, and address secondary conditions of TBI, including its emotional and psychosocial effects.

A large portion of NICHD research on TBI is supported through the TBI and Stroke Rehabilitation (TSR) Program within the National Center for Medical Rehabilitation Research (NCMRR).

Diagnosing and assessing TBI can be challenging, but doing so effectively is essential to improving outcomes for TBI patients. NICHD-supported researchers work to improve diagnostics through such efforts as a study to find an accurate serum marker for mild TBI. They are also looking for more effective and faster methods to measure the effects of TBI, such as a device for monitoring problems with balance.

Other NICHD-supported research focuses on sports-related brain injury, including the rapid detection of concussion. For example, Institute-supported researchers are exploring a sports-related head-impact alert system as well as a helmet testing method that better mimics conditions of real game play. Read more about NICHD research on concussion and sports and other NICHD research on TBI.

Disabilities resulting from a TBI depend upon the severity of the injury, the location of the injury, and the age and general health of the individual. Patients with TBI often abruptly experience impaired medical decision-making capacity at time of injury, and this impairment can continue during rehabilitation and afterwards. These types of impairments create ethical issues for physicians, patients, and families. 

Scientists conducted a study investigating the medical decision-making capacity in patients with acute TBI, including individuals with moderate/severe injury, mild injury, or no injury at all. Scientists compared patients' capacity to consent to medical treatment on 5 standards (expressing choice, reasonable choice, appreciation, reasoning, and understanding). One month after injury, the mild injury TBI group performed just as well as the healthy control subjects on informed consent standards. However, the moderate/severe TBI group was impaired on almost all standards relative to both the healthy control groups and the mild injury TBI group. Mild/moderate or severe impairments ratings on the three clinically complex standards (understanding, reasoning, appreciation) occurred in 10% to 30% of patients with mild TBI, 50% of patients with complicated mild TBI, and 50% to 80% of patients with moderate/severe TBI. Medical decision-making capacity was largely intact in patients with mild TBI, but was impaired in patients with complicated mild TBI and moderate/severe TBI. (PMID: 22496195)

The TSR Program has supported several projects on treatment for TBI, including medications. A variety of treatments are known to promote recovery from the physical, emotional, and cognitive problems TBI may cause. The types and extent of treatments depend on the severity of the injury and its specific location in the brain.

Citicoline, a naturally occurring compound in the human body, has been widely used abroad for the treatment of traumatic brain injury. However, citicoline has not been approved by the U.S. Food and Drug Administration for TBI treatment in the United States. The compound has been tested in preliminary clinical trials, but in most of these studies citicoline did not appear effective in treating TBI.

NIH-supported scientists conducted a new large-scale clinical trial that tested citicoline across a broad spectrum of TBI, from mild to severe. Researchers studied the effects of citicoline on the functional and cognitive status of over 1,200 patients with mild, moderate, or severe TBI. The investigators assessed effects both in the acute (early) treatment phase and over time (at 3 months and 6 months). They found no significant difference, in terms of TBI patients' functional or cognitive status, between patients given a placebo―a simulated "drug" without medical effect―and those treated with citicoline. (PMID: 23168823)

Scientists are also testing potential medications in laboratory animals to determine if they can lessen or halt the ongoing nerve and tissue damage that continues over time after the initial TBI. In one study, researchers studied the effects of carbamylated erythropoietin (CEPO). They found that three doses of CPO, administered 6, 24, and 48 hours after injury, reduced TBI lesion volume, improved recovery in sensory and movement function as well as in memory in learning, and improved growth of nerve cells and blood vessels. (PMID: 21073254)

In another experiment, a different substance, called thymosin beta-4, did not affect the volume of the TBI lesion but otherwise had similarly positive effects on blood vessel and nerve growth and on the rats' functioning and learning. (PMID: 20486893) In a third study, researchers tested a dietary intervention to restore functioning in the hippocampus. They found that feeding rats an amino acid preparation seven days after TBI restored to normal the efficacy of nerve connections that had been damaged by the injury, and also improved cognitive functioning of the rats. (PMID: 19995960

Investigators are also testing new combinations of therapies that had been shown previously to have positive effects when used individually. For example, investigators found that giving experimental rats an agent (tacrolimus, or FK506) along with radical, whole-body chilling (hypothermia), beginning an hour or 90 minutes after TBI, extended the period in which FK506 helped protect the brain from ongoing processes of injury. (PMID: 21157473) In another study in rats, NICHD-supported researchers found that the brain-protective effects of progesterone, which is currently in human trials for use after TBI, are further enhanced by administering it with vitamin D hormone shortly after TBI. The research suggests that these two hormones in combination can preserve memory. (PMID: 22570859)   

NICHD-supported researchers also are looking at rehabilitation methods, procedures, and therapies to improve long-term outcomes and quality-of-life for TBI patients and their families. For example:

  • A five-year, nine-site study focuses on helping identify which medical procedures and therapy interventions are associated with better long-term outcomes.
  • A clinical trial is testing a novel program to help patients regain control over problematic anger subsequent to TBI.
  • Researchers are evaluating a patient-education program designed to improve the general emotional and behavioral functioning of TBI patients.

Secondary conditions following TBI can significantly impede recovery and rehabilitation. NICHD supports research to understand and treat many of these conditions, including depression. In the first large-scale study on TBI and depression, NICHD-funded researchers found that the rate of depression among TBI survivors was eight times greater than in the general population. The study also suggested that it is possible to identify depression within the first few months after a TBI, contradicting prior theories. Other research explores whether people with TBI respond to antidepressant treatment in the same way as people who have not experienced TBI. Read more about NICHD TBI and depression research.

Within the Division of Intramural Research (DIR), the Program on Pediatric Imaging and Tissue Sciences also conducts research on ways to evaluate TBI using imaging technology.

The ability to explore the microstructure and architectural organization of the brain promotes understanding of TBI mechanisms and possible interventions. The Program's Section on Tissue Biophysics and Biomimetics invents, develops, and implements novel quantitative in vivo methods for imaging tissues and organs. For more information about this work, read the Program's section of the DIR's 2012 annual report.  

Intramural researchers who study brain activity contribute to our understanding of the cells and systems involved in TBI. For example, researchers in NICHD's Section on Cellular and Synaptic Physiology and their colleagues recently published results of a study describing the shifting roles of certain brain cells known as dentate gyrus granule cells in controlling memory. (PMID: 22365813)

Other Activities and Advances

  • The NCMRR established the Traumatic Brain Injury Clinical Trials Network, which crafted guidelines for measuring the outcomes of TBI clinical trials as a way to standardize measures to allow for comparisons in clinical trials. The Network's primary activities also included the creation of a working definition of TBI and development of the first clinical treatment guidelines for the entire continuum of TBI care.
  • The NICHD has collaborated with leaders at the NIH and other agencies to improve outcomes for people with TBI. The Institute played a key role in the 1998 Consensus Development Conference on the Rehabilitation of Persons with Traumatic Brain Injury. In 2011, NICHD scientists were appointed to a blue ribbon panel established to review medical rehabilitation research at the NIH and identify promising research opportunities.
  • The Institute is participating in a Center for Neuroscience and Regenerative Medicine External Web Site Policy project to improve the accuracy and reproducibility of findings using diffusion tensor imaging (DTI) in TBI research.
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