The Neuropathology Core, co-located at USUHS and VA Boston Biorepository Brain Banks, manages the collection of brain specimens from participants using an existing national network of dieners and neuropathologists. The Core also catalogs and stores these tissues for use by qualified investigators from within or outside the CENC. The Core administers requests for use of these tissues according to sample sharing policies of the Consortium, and tracks the results of these collaborative studies.
TBI due to exposure to explosive blasts (mostly related to IEDs) is responsible for over 70% of the combat casualties associated with Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF) and Operation New Dawn (OND)[3,4]. While most of these TBIs are classified as mild, they can have disabling long-term consequences. Mild TBI (mTBI) is widely recognized as the signature injury of modern warfare, and yet little is known about its acute effects on the brain or its long-term consequences, particularly in individuals who have suffered multiple mTBIs. With the current practice of repeated redeployment, the opportunities for Service Members to experience multiple TBIs increase dramatically. While much work has been done to study TBI in animal model systems, in humans, the specific details of the neuropathologic lesions induced by mTBI, particularly those resulting from exposure to IED blast waves and the subsequent accompanying impact trauma remain unknown. Moreover, the repair responses of the brain to such injuries and their long-term consequences are similarly unclear. The primary reason for this major gap in knowledge has been the lack of available brain specimens for morphologic and molecular study derived from deceased active or returned combatants who suffered mTBI. This Core directly addresses this issue.
In order for rational methods for diagnosis, treatment and prevention of such consequences to emerge, access to brain specimens such as will be collected and made available to researchers through the proposed Brain Tissue Repository will be required. This is why this component of the proposed CENC is absolutely critical to the overall effort of the Consortium program.
Studies of the brains of former NFL football players serve as an example of how research based on a brain repository can dramatically increase knowledge and fundamentally change outlook and approach to a medical problem. Before this work began, the NFL primarily focused on musculoskeletal injuries. Among league officials and team physicians, the concept that repeated mild head trauma could trigger a cascade of neurodegeneration leading to profound neurocognitive deficits and behavioral changes, a disease known as dementia pugilistica or chronic traumatic encephalopathy (CTE), was viewed as an exceedingly rare phenomenon, if it occurred at all. In just over a few years of research, this viewpoint completely changed. The brains derived from a number of former NFL football players as well as other athletes who suffered repeated head trauma, have shown widespread aggregates of abnormal tau proteins, mostly in the form of numerous neurofibrillary tangles (NFTs)(Omalu, DeKosky et al. 2005; Omalu, DeKosky et al. 2006; McKee, Cantu et al. 2009; Omalu, Hamilton et al. 2010; McKee, Stein et al. 2012). These NFTs display a distinct and recognizable topographic distribution that does not occur in any other form of neurodegeneration, which allows for the neuropathologic diagnosis of CTE (Hof, Bouras et al. 1992; Geddes, Vowles et al. 1999; McKee, Stein et al.
2012). Based on the collection and study of these donated brains, the serious consequences to brain structure and function related to repeated head trauma in contact sports is now being discussed and re-evaluated at both societal and scientific levels.
Traumatic brain injury due to exposure to explosives has been in the combat theater for at least 100 years. If rational approaches to prevention, rehabilitation and therapy are to be considered by the military, then one must have available the data that will emerge from research based on human tissue samples harvested by the proposed Brain Repository. Military and other research funding agencies currently support numerous efforts to develop and characterize various animal models of both blast and impact TBI. Nevertheless, without knowing the results of human cellular and molecular studies, one cannot determine the validity of any of these models.
The ability to identify those animal models that best reproduce what service members experience after TBI on the field of combat will greatly help maximize the effectiveness of this important avenue of research. Finally, correlating careful neuropathologic examination with neuroimaging and clinical symptoms will help guide diagnostics for both those who have defended the nation and who will do so in the future.
- Obtain brain specimens on all cases referred to the brain bank among those enrolled in CENC studies who die and for whom anatomical consent for brain donation is provided.
- Accession the donation of the brain specimen derived from any Veteran who had been deployed in OIF, OEF or OND, who dies and the next-of-kin requests brain donation for research studies of TBI.
- Dissect and preserve the brain tissues using standard protocol to maximize their use for TBI research.
- Perform detailed neuropathologic evaluations of all accessioned brain specimens and issue a complete diagnostic neuropathology report.
- Document the extent and distribution of relevant lesions present within each brain specimen.
- Make tissue specimens available to qualified researchers engaged in TBI-related research.
- Maintain permanently all pertinent specimen-related data and the results of the detailed neuropathologic studies in a manner accessible to all investigators within the Consortium as well as more broadly to other qualified researchers.
Contact: Daniel Perl, MD; firstname.lastname@example.org