National Institutes of Health - NIH/NINDS

The National Institute of Neurological Disorders and Stroke (NINDS) along with the National Institute of Aging at the NIH have sponsored a great deal of research in areas that related to the #C4CT.

NIH supports research to develop interventions that prevent immediate and delayed problems from TBI, from laboratory studies in animals through large, multi-site clinical trials. NIH research has contributed to better critical care that has dramatically improved survival from severe TBI. NINDS and partners in Europe and Canada recently launched the International TBI Research Initiative. This prospective, observational study of 3,000 adults and children with TBI in the United States, coordinated with large studies by the European Union and the Canadian Institute of Health Research, will inform TBI classification and identify those therapies associated with the best outcome. NIH laid the foundation for meaningful comparison across these and other future studies by working with the research community and other federal agencies through the NINDS Common Data Elements program to harmonize the data that are collected and the way data are categorized. The DOD- and NIH-led Federal Interagency TBI Informatics System (FITBIR) provides a database for sharing information from these and other TBI studies among qualified investigators.

Progress in basic neuroscience has yielded advances in understanding the biology of the brain in health and disease, and an impressive array of tools to study the brain that will drive progress against TBI, dementia, and other brain disorders. The Human Connectome Project, for example, is applying advances in computer science, math, and diffusion tensor MRI brain imaging to develop a complete picture of the brain’s functional architecture in more than 1000 people, that is, a map of how different brain areas are connected and work together in the living brain. Pathologic studies demonstrate that damage, called “shear injury,” in the brain’s connections or “white matter” is common in moderate and severe TBI. Shear injury, which may occur diffusely throughout the brain, is relatively invisible with conventional imaging techniques. The Connectome will greatly enhance the ability to recognize and quantify the disruption in communication pathways between brain regions, and why some people’s brains compensate better than others. Complementing this project at a more fine grained level of analysis, the President’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is developing tools with the spatial and temporal resolution to yield a dynamic, real time picture of how circuits formed by millions of interconnected nerve cells and synapses work. The BRAIN Initiative may ultimately yield insights about how TBI, Alzheimer’s, and other disorders affect the 10 functioning of important brain circuits and how the brain attempts to recover or compensate for these changes.

This January, an NINDS intramural research team showed the power of applying emerging methods from basic neuroscience to TBI. These researchers developed a novel mouse model of mild TBI and used advanced microscopy and cell labeling techniques to watch in real time in living animals how particular types of cells responded to mild TBI from the start. The investigators saw the swarming of immune cells and leakage of dye out of blood vessels on the surface of the brain during the initial inflammatory response and the recruitment of brain supporting cells that reconstituted damaged protective barriers. Using MRI brain imaging, the team was also able to detect similar dye leakage from surface blood vessels in humans after concussion, underlining the likely relevance of the animal studies. Because researchers could watch the cells’ responses to pharmacological agents, they could analyze how chemical signals orchestrate damage and repair responses and test potential interventions that target these mechanisms. Methods like these promise to greatly increase our understanding of how the brain reacts to TBI and why there may be long term consequences.

To answer the key challenges discussed today, NIH supports a full spectrum of research and works closely with others, including DOD, CDC, and the international scientific community. With great anticipation we await the introduction of new MRI and PET brain imaging methods that will enable us to identify and quantify important brain changes in living TBI survivors for the first time. Longitudinal studies can then determine what occurs in the brain that leads to delayed cognitive decline, and whether Alzheimer’s disease is more likely to occur. New structural and molecular imaging techniques may also enable scientists to identify and track markers of the neurodegenerative process over time, which can provide targets against which to test new therapies. Progress is imperative because of the enormous impact of TBI and dementia on individuals and their families, on the public health, and on the economy of the United States and the world.

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