120 YEARS OF ADVANCES FOR MILITARY AND PUBLIC HEALTH
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Ongoing studies conducted by the Center for Military Psychiatry and Neuroscience have sought to further the understanding of how TBI affects the brain.
that continues to show TBI-specific biomarkers – higher- or lowerthan-normal levels of proteins and enzymes associated with specific neurological mechanisms – in brain tissue and/or cerebrospinal fluid (CSF) and serum. These biomarkers have been detected and measured in animal models, and increasingly in human subjects in clinical trials, and they show great promise – but the science is still too young to link the presence of specific biomarkers to an indication for certain drugs. “Their studies have identified some pretty good TBI-related biomarkers – biomarkers that have sensitivity and specificity,” said Col. Paul Bliese, director of the CMPN. “This has a lot of applicability to places like Iraq or Afghanistan, where someone may encounter many other kinds of injuries, but where one isn’t necessarily sure whether they’ve suffered a traumatic brain injury as well.” There is no drug therapy currently approved as a standard of care for TBI. The directorate’s approach to discovering and developing effective TBI drugs is via cooperative research and development agreements (CRADAs) with pharmaceutical companies, as well as collaborative efforts with the Army’s Operation Brain Trauma Therapy (OBTT) program, a multicenter pre-clinical drug-screening consortium. Using animal models of severe TBI, the efforts of the BTNN research team have demonstrated what drugs are highly neuroprotective and anticonvulsant and therefore suitable for the launch of Phase I clinical trials to demonstrate safety and bioavailability in normal volunteers. With Phase I trials complete for one such drug, the next
step is already under way – a Phase II trial, with cost sharing between private industry and the DoD, of the drug’s safety and efficacy in moderate and severe TBI patients. TBI-related brain physiology is still not completely understood, and two decades’ worth of clinical trials have not produced a single drug capable of reliably protecting the brain from TBI-related harm. Singledrug “monotherapies,” which target individual or simple brain mechanisms, simply haven’t proven adequate to address the complexities of the injured brain, and BTNN researchers are among those turning increased attention to combination drug therapies that achieve efficacy through synergistic drug-pair interactions. The center’s neuroprotection and neurorestoration researchers have also contributed to research in non-pharmacological TBI treatments, such as therapies in which human amnion-derived stem cells, transplanted into injured brain tissue, have demonstrated an ability to protect against neural tissue damage and motor deficits. BTNN Branch researchers have also conducted pre-clinical investigations, in animal models, into an innovative method for selectively cooling the brain post-trauma. The use of a cooling cuff placed around the common carotid artery can achieve rapid and sustained reductions in brain temperatures – which in turn reduces intracranial pressure, inflammation of damaged tissues, brain edema, and the permeability of the protective blood/brain barrier (BBB) – without adversely influencing core body temperature.
CMPN