Contact: Gina Orlando, (617) 638-8490, firstname.lastname@example.org
(Boston) – Robert J. Nicoletta, MD has joined Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) as an orthopaedic surgeon and assistant professor and co-director of sports medicine in the department of orthopaedic surgery. Nicoletta will see patients at both the Shapiro Ambulatory Care Center at BMC and the Ryan Center for Sports Medicine and Rehabilitation at Boston University starting August 1.
Nicoletta is a board-certified orthopaedic surgeon with specialty training in the field of sports medicine. His clinical interests include arthroscopic procedures of the knee and shoulder including anatomic and double bundle ACL reconstruction, cartilage injuries in the knee and shoulder rotator cuff injuries and instability.
Team physician for numerous local high schools, collegiate and professional athletic teams, Nicoletta most recently served as a team physician at Boston College, the Boston Cannons Men’s Professional Lacrosse team and the Boston Breakers Women’s Professional Soccer team. Before coming to Boston University Medical Campus, Nicoletta served as chief of orthopaedic surgery and sports medicine at St. Elizabeth’s Medical Center.
Recently named to the national List of 65 Outstanding Shoulder Surgeons and Specialists by Becker’s Orthopedic and Spine Review, Nicoletta completed a fellowship in sports medicine and arthroscopic surgery at BMC after earning his medical degree from Syracuse University.
Contact: Gina Orlando, 617-638-8490, email@example.com
(Boston) – Researchers from Boston University School of Medicine (BUSM) have found an association between childhood physical and sexual abuse and age at menarche. The findings are published online in the Journal of Adolescent Health.
Researchers led by corresponding author, Renée Boynton-Jarrett, MD, assistant professor of pediatrics at BUSM, found a 49 percent increase in risk for early onset menarche (menstrual periods prior to age 11 years) among women who reported childhood sexual abuse compared to those who were not abused. In addition, there was a 50 percent increase in risk for late onset menarche (menstrual periods after age 15 years) among women who reported severe physical abuse in childhood. The participants in the study included 68,505 women enrolled in the Nurses’ Health Study II, a prospective cohort study.
“In our study child abuse was associated with both accelerated and delayed age at menarche and importantly, these associations vary by type of abuse, which suggest that child abuse does not have a homogenous effect on health outcomes,” said Boynton-Jarrett. “There is a need for future research to explore characteristics of child abuse that may influence health outcomes including type, timing and severity of abuse, as well as the social context in which the abuse occurs.”
Child abuse is associated with a significant health burden over the life course. Early menarche has been associated with risks such as cardiovascular disease, metabolic dysfunction, cancer and depression, while late menarche has been associated with lower bone mineral density and depression.
“We need to work toward better understanding how child abuse influences health and translate these research findings into clinical practice and public health strategies to improve the well-being of survivors of child abuse,” added Boynton-Jarrett.
This research was supported by the William T Grant Foundation, the Charles Hood Foundation, and the Building Interdisciplinary Research Careers in Women’s Health K12 HD043444 NIH Office of Women’s Health Research funded data analysis, manuscript preparation. The Nurses’ Health Study II is supported by Public Health Service grant CA50385 from the National Cancer Institute, National Institutes of Health, and U.S. Department of Health and Human Services. The Nurses‟ Mothers‟ Cohort Study was funded by the Intramural Research Program of the National Cancer Institute, Research Contract N02-RC-17027 from the National Cancer Institute, and by P.O. 263 MQ 411027 from the National Cancer Institute. The 2001 supplemental violence assessment questionnaire was funded by R01 HL064108.
BUSM study identifies Adenosine Receptor’s role in regulating high fat diet-induced obesity and Type 2 Diabetes
Contact: Jenny Eriksen Leary, 617-638-6841, firstname.lastname@example.org
(Boston) – A recent study led by Boston University School of Medicine (BUSM) demonstrates that the A2b-type adenosine receptor, A2bAR, plays a significant role in the regulation of high fat, high cholesterol diet-induced symptoms of type 2 diabetes. The findings, which are published online in PLoS ONE, also identify A2bAR as a potential target for the treatment of type 2 diabetes.
Katya Ravid, DSc/PhD, professor of medicine and biochemistry and director of the Evans Center for Interdisciplinary Biomedical Research at BUSM, led this study. Colleagues from Ravid’s lab who collaborated on this research include Hillary Johnston-Cox, BSc (MD/PhD, 2014) and Milka Koupenova-Zamor, PhD. Noyan Gokce, MD, associate professor of medicine at BUSM, and Melissa Farb, PhD, a postdoctoral fellow at BUSM, also collaborated on the study.
Diets that are high in fat and cholesterol induce changes in how the body regulates blood glucose levels. Exercise induces an increased production adenosine, a metabolite produced naturally by cells. A2bAR, a naturally occurring protein receptor found in the cell membrane, is activated by adenosine. This receptor is known to play an important role in regulating inflammation, which is associated with type 2 diabetes and obesity.
To examine the association of A2bAR activation with a diet high in fat and cholesterol, the researchers used an experimental model that lacked A2bAR and compared the results with a control group. When the experimental model group was given a diet high in fat and cholesterol, there was an increase in the development of obesity and signs of type 2 diabetes. The signs demonstrated in the study included elevated blood glucose levels and increased in insulin levels. When the control group was given the same diet, however, the levels of A2bAR increased, resulting in decreased insulin and glucose levels and obesity.
A novel link also was identified between the expression of A2bAR, insulin receptor substrate 2 (IRS-2) and insulin signaling. The results showed that the level of IRS-2, a protein that has previously been shown to mediate the effect of insulin, was impaired in tissues of the experimental model lacking A2bAR, causing higher concentrations of blood glucose. When A2bAR was activated in the control group using a pharmacologic agent with a diet high in fat and cholesterol, the level of IRS-2 was upregulated, lowering blood glucose.
“The pharmacologic activation of A2bAR demonstrated its newly identified role in signaling down to regulate the levels of IRS-2, which then improved the signs of high fat diet-induced type 2 diabetes,” said Ravid.
The prevalence of type 2 diabetes and obesity continues to increase in developed countries and both factors are known to contribute to the development of cardiovascular disease. According to the World Health Organization, 346 million people worldwide have diabetes and 90 percent of those people have type 2 diabetes.
To correlate these results in humans, the researchers then examined fat tissue samples from obese individuals. The results showed that A2bAR expression is high in fat from obese individuals, marked by inflammation, compared to lean ones, and is strongly correlated with IRS-2 expression.
“Our study suggests the important role of A2bAR in maintaining the level of IRS-2, a regulator of glucose and insulin homeostasis,” added Ravid.
This study was funded in part by the National Heart, Lung and Blood Institute under award numbers HL93149 (Katya Ravid) and HL084213 (Noyan Gokce). Click on the following link to view the study online: http://dx.plos.org/10.1371/journal.pone.0040584.
Contact: Jenny Eriksen Leary, 617-638-6841, email@example.com
(Boston) – A study conducted at Boston University School of Medicine (BUSM) demonstrates an effective combination therapy for breast cancer cells in vitro. The findings, published in the July 2012 issue of Anticancer Research, raise the possibility of using this type of combination therapy for different forms of breast cancer, including those that develop resistance to chemotherapy and other treatments.
The study was led by researchers at the Boston University Cancer Center. Sibaji Sarkar, PhD, adjunct instructor of medicine at BUSM, is the study’s corresponding author.
According to the Centers for Disease Control and Prevention, breast cancer is the most common cancer among women in the United States aside from non-melanoma skin cancer. Breast cancer also is one of the leading causes of cancer death among women of all races and Hispanic origin populations.
Triple negative breast cancer, which accounts for approximately 14 to 20 percent of all breast cancer cases, is a type of the disease that occurs when the cancer cells lack hormone receptors, including the receptor called HER-2, and typically will not respond to hormone and herceptin-based therapies. Triple negative breast cancer occurs more often in African-American women and is considered to be a more aggressive form of the disease with higher rates of recurrence and mortality than other forms of breast cancer.
“Cancer is like a car without brakes. Cell growth speeds up and it doesn’t stop,” said Sarkar. “When expressed, tumor suppressor genes, which work in a protective way to limit tumor growth, function as the brakes. They are not expressed in most cancers, causing the cancer to grow and potentially metastasize.”
A major focus in the area of anti-cancer drug development is to find a way to re-express tumor suppressor genes so that they can help inhibit cancer cell growth. Some tumor suppressor genes are imprinted, meaning that from the two genes inherited from the mother and father, only one of the genes is functional. In cancer, both imprinted tumor suppressor genes may become non-functional and unable to stop tumor growth.
The researchers tested, in vitro, a combination therapy of an epigenetic drug with a protease inhibitor on breast cancer cell lines that are hormone responsive and breast cancer lines, like triple negative, that are not hormone responsive. They utilized histone deacetylases inhibitors (HDACi) and calpeptin, which inhibits calpain, a protein involved in the regulation of signaling proteins. Calpain inhibition is being studied as a potential treatment model for blood clots and other neurological diseases.
In this study, they found that the combination therapy both inhibited cell growth and increased cell death in both cancer cell lines by inducing cell cycle arrest and cell death. However, the mechanism of how the combination therapy stops the cells from growing was different. Cells in the hormone responsive line stopped the cell cycle in an earlier phase compared to the non-hormone responsive cells. In the triple negative breast cancer cell line, the inhibitors allowed an imprinted tumor suppressing gene, ARHI, to re-express, which helped stop the growth of the cancer cells and led to cancer cell death.
“The study data demonstrates that HDACi’s bring back the brakes of the car, halting cell growth and promoting cell death,” added Sarkar, who also is a faculty member at the Genome Science Institute at Boston University. “These results provide a model to investigate the re-expression of tumor suppressor genes, including imprinted genes, in many forms of breast cancer.”
This study needs further investigation but raises the possibility of using this type of combination therapy for diverse types of breast cancers including those that are hormone refractory and develop drug resistance to conventional chemotherapy.
This study was funded by the American Cancer Society.
Contact: Jenny Eriksen Leary, 617-638-6841, firstname.lastname@example.org
(Boston) – A recent study led by researchers at Boston University School of Medicine (BUSM) revealed that the FOXO1 gene may play an important role in the pathological mechanisms of Parkinson’s disease. These findings are published online in PLoS Genetics, a peer-reviewed open-access journal published by the Public Library of Science
The study was led by Alexandra Dumitriu, PhD, a postdoctoral associate in the department of neurology at BUSM. Richard Myers, PhD, professor of neurology at BUSM, is the study’s senior author.
According to the Parkinson’s Disease Foundation, 60,000 Americans are diagnosed with Parkinson’s disease each year and approximately one million Americans are currently living with the disease.
Parkinson’s disease is a complex neurodegenerative disorder characterized by a buildup of proteins in nerve cells that lead to their inability to communicate with one another, causing motor function issues, including tremors and slowness in movement, as well as dementia. The substantia nigra is an area of the midbrain that helps control movement, and previous research has shown that this area of the brain loses neurons as Parkinson’s disease progresses.
The researchers analyzed gene expression differences in brain tissue between 27 samples with known Parkinson’s disease and 26 samples from neurologically healthy controls. This data set represents the largest number of brain samples used in a whole-genome expression study of Parkinson’s disease to date. The novel aspect of this study is represented by the researchers’ emphasis on removing possible sources of variation by minimizing the differences among samples. They used only male brain tissue samples that showed no significant marks of Alzheimer’s disease pathology, one of the frequently co-occurring neurological diseases in Parkinson’s disease patients. The samples also had similar tissue quality and were from the brain’s prefrontal cortex, one of the less studied areas for the disease. The prefrontal cortex does not show neuronal death to the same extent as the substantia nigra, although it displays molecular and pathological modifications during the disease process, while also being responsible for the dementia present in a large proportion of Parkinson’s disease patients.
Results of the expression experiment showed that the gene FOXO1 had increased expression in the brain tissue samples with known Parkinson’s disease. FOXO1 is a transcriptional regulator that can modify the expression of other genes. Further examination of the FOXO1 gene showed that two single-nucleotide polymorphisms (SNPs), or DNA sequence variations, were significantly associated with age at onset of Parkinson’s disease.
“Our hypothesis is that FOXO1 acts in a protective manner by activating genes and pathways that fight the neurodegeneration processes,” said Dumitriu. “If this is correct, there could be potential to explore FOXO1 as a therapeutic drug target for Parkinson’s disease.”
Research reported in this publication was supported in part by the National Institute of Neurological Disorders and Stroke under award number 1R01NS076843-01, the Cogan Family Foundation, the Robert P. & Judith N. Goldberg Foundation and the William N. and Bernice E. Bumpus Foundation.
Contact: Gina DiGravio, (617) 638-8480, email@example.com
(Boston) — In a genome-wide association (GWA) study, researchers from Boston University Schools of Medicine (BUSM) and Public Health (BUSPH), have identified several genes which influence degeneration of the hippocampus, the part of the brain most associated with Alzheimer disease (AD). The study, which currently appears online as a Rapid Communication in the Annals of Neurology, demonstrates the efficacy of endophenotypes for broadening the understanding of the genetic basis of and pathways leading to AD.
AD is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making AD effectively untreatable.
GWA studies using very large samples have increased the number of robust associations to 10 genes, including APOE. However, these genes account for no more than 35 percent of the inherited risk of AD and most of the genetic underpinning of the disorder remains unexplained. According to the researchers, magnetic resonance imaging (MRI) of the brain provides in vivo quantitative measures of neurodegenerative and cerebrovascular brain injury that may represent AD-related changes long before clinical symptoms appear. These measures are more powerful than comparisons of individuals with AD with cognitively healthy persons because they avoid misclassification of normal persons who will develop disease in the future.
BUSM researchers conducted a two-stage GWA study for quantitative measures of hippocampal volume (HV), total cerebral volume (TCV) and white matter hyperintensities (WMH). Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African-American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer’s Genetic Epidemiology) Study. In addition, similar MRI measures were obtained from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls (all Caucasian) in the AD Neuroimaging Initiative (ADNI) Study. The MIRAGE Caucasian families and ADNI subjects were included in the first stage and the MIRAGE African American families were added in stage two. Results from the two Caucasians data sets were combined by meta-analysis.
In stage two, one genetic marker (i.e. single nucleotide polymorphism or SNP) from each of the gene regions that were most significantly associated with AD in the Caucasian data sets was evaluated in the African-American data set.
Novel genome-wide significant associations were observed for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set.
“Our two-stage GWAS identified highly significant associations between a measure of degeneration in the brain region most strongly correlated with AD and several genes in both Caucasian and African American samples containing AD, cognitively impaired and cognitively healthy subjects. One of these associations was with the ε4 variant of APOE which is the most well-established genetic risk factor for AD. Other associations were demonstrated with markers in F5/SELP, LHFP, and GCFC2, genes not previously implicated in this disease” explained senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM. He also noted, “previous studies showed that blood level of P-selectin (the protein encoded by SELP) has been correlated with rate of cognitive decline in AD patients.”
Farrer believes it is very likely that the number and specificity of these associations will increase in future studies using larger samples and focused on additional precise structural and functional MRI measures. “These findings will inform experiments designed to increase our understanding of disease-causing mechanism and may lead to new therapeutics targets,” added Farrer.
Researchers from Massachusetts General Hospital, Indiana University School of Medicine and University of California at Davis also collaborated on this study.
This study was supported by the National Institute on Aging (NIA), the Dana Foundation and the National Institutes of Health Clinical and Translational Science Institute. ADNI is funded by the NIA and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Merck and Co., Novartis AG, Pfizer, F. Hoffman-La Roche, Schering-Plough, Synarc, and Wyeth, as well as nonprofit partners the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).
Contact: Gina DiGravio, 617-638-8480, firstname.lastname@example.org
(Boston) – Researchers from Boston University Schools of Medicine and Public Health (BUSM, BUSPH), along with the VA Boston Healthcare System and Harvard Medical School, have found inpatient medical procedures increased more among non-elderly, lower- and medium- income populations, Hispanics and whites, after health care reform went into effect in Massachusetts. The findings, which currently appear in Medical Care, suggest improved access to outpatient care for vulnerable subpopulations since health care reform took effect.
The 2006 Massachusetts health reform implementation substantially decreased the number of uninsured in the state. Yet, little is known about the reform’s impact on actual healthcare utilization among poor and minority populations, particularly for inpatient surgical procedures that are commonly initiated by outpatient physician referral.
Researchers used discharge data on Massachusetts hospitalizations for 21 months preceding and following health reform implementation (July 2006–December 2007). They identified all non-obstetrical major therapeutic procedures for patients 40 years and older and for which more than 70 percent of hospitalizations were initiated by an outpatient physician referral. Specifically, they compared pre- and post-reform utilization of major therapeutic inpatient surgical procedures predominantly scheduled by outpatient referrals among non-elderly Massachusetts adults, and found greater overall increases for lower income cohorts compared to the highest income cohort, and for Hispanics compared to whites.
“Prior to reform, both blacks and Hispanics had lower rates of these procedures compared to whites. As 90 percent of all surgeries came from outpatient physician referral, these findings suggest a meaningful improvement in access to outpatient care for the surgeries studied, especially those living in lower income areas,” explained senior author Nancy Kressin, PhD, professor of medicine at BUSM.
Findings of significant post-reform expansion in procedure use for Hispanics and lower area income patients are consistent with the relatively larger gains in insurance coverage among these subpopulations. These findings suggest potentially improved access to outpatient care and may reflect demand built up prior to reform when individuals were uninsured. “Whether such improved access – a crucially important first step to improving equity in access and outcomes – translates into improved clinical outcomes at a reasonable cost merits further study,” added Kressin.
Funding for the study was provided by the National Heart, Lung and Blood Institute Center for Health Insurance Reform and Cardiovascular Outcomes and Disparities.
Contact: Gina DiGravio, 617-638-8480, email@example.com
(Boston) – Researchers from Boston University School of Medicine (BUSM) have identified a novel group of proteins that accumulate in the brains of patients with Alzheimer’s disease. These findings, which appear online in the Journal of Neuroscience, may open up novel approaches to diagnose and stage the progression likelihood of the disease in Alzheimer patients.
Alzheimer’s disease is presumed to be caused by the accumulation of β-amyloid, which then induces aggregation of a neuronal protein, called tau, and neurodegeneration ensues. The diagnosis of Alzheimer’s disease focuses on β-amyloid and tau protein, with much attention focusing on radiolabeled markers that bind to β-amyloid (such as the compound PiB). However, imaging β-amyloid is problematic because many cognitively normal elderly have large amounts of β-amyloid in their brain, and appear as “positives” in the imaging tests.
Therapeutic approaches for Alzheimer’s disease generally have focused on β-amyloid because the process of producing a neurofibrillary tangle composed on tau protein has been poorly understood. Hence, few tau therapies have been developed. According to the researchers, this study makes important advances on both of these fronts.
The BUSM researchers identified a new group of proteins, termed RNA-binding proteins, which accumulate in the brains of patients with Alzheimer’s disease, and are present at much lower levels in subjects who are cognitively intact. The group found two different proteins, both of which show striking patterns of accumulation. “Proteins such as TIA-1 and TTP, accumulate in neurons that accumulate tau protein, and co-localize with neurofibrillary tangles. These proteins also bind to tau, and so might participate in the disease process,” explained senior author Benjamin Wolozin, MD, PhD, a professor in the departments of pharmacology and neurology at BUSM. “A different RNA binding protein, G3BP, accumulates primarily in neurons that do not accumulate pathological tau protein. This observation is striking because it shows that neurons lacking tau aggregates (and neurofibrillary tangles) are also affected by the disease process,” he added.
The researchers believe this work opens up novel approaches to diagnose and stage the likelihood of progression by quantifying the levels of these RNA-binding protein biomarkers that accumulate in the brains of Alzheimer patients.
Wolozin’s group also pursued the observation that some of the RNA binding proteins bind to tau protein, and tested whether one of these proteins, TIA-1, might contribute to the disease process. Previously, scientists have demonstrated that TIA-1 spontaneously aggregates in response to stress as a normal part of the stress response. Wolozin and his colleagues hypothesize that since TIA-1 binds tau, it might stimulate tau aggregation during the stress response. They introduced TIA-1 into neurons with tau protein, and subjected the neurons to stress. Consistent with their hypothesis, tau spontaneously aggregated in the presence of TIA-1, but not in the absence. Thus, the group has potentially identified an entirely novel mechanism to induce tau aggregates de novo. In future work, the group hopes to use this novel finding to understand how neurofibrillary tangles for in Alzheimer’s disease and to screen for novel compounds that might inhibit the progression of Alzheimer’s disease.
Funding for this study was provided by grant awards from the National Institutes of Health (National Institute of Neurological Disorders and Stroke; National Institute of Environmental Health Sciences and National Institute on Aging).
Contact: Gina Orlando, (617) 638-8490, firstname.lastname@example.org
(Boston) – Boston University School of Medicine (BUSM) researchers recently uncovered a brain signaling pathway responsible for regulating the renal excretion of sodium. The findings appear in the Journal of the Federation of American Societies for Experimental Biology.
Hypertension, or chronic high blood pressure, affects one-third of adults, significantly increasing cardiovascular risk and mortality. Approximately 50 percent of hypertensive patients are salt-sensitive and exhibit an increase in blood pressure following salt-intake.
According to the researchers, little is known about the mechanisms acting in the brain to control the removal of dietary salt from the body through the kidneys. “Our data shows that changes in dietary sodium intake evoked natural site-specific changes in brain hypothalamic paraventricular nucleus (PVN) Gαi2 protein levels,” said Senior Author Richard Wainford, PhD, assistant professor of pharmacology and experimental therapeutics.
Wainford and his team explored the role of Gαi2 signal transduction proteins in the brain pathways activated to regulate salt and water excretion and subsequently blood pressure. They identified a previously unknown role of PVN Gαi2-subunit proteins as a central mechanism mediating the suppression of renal sympathetic nerve traffic to the kidneys and the renal excretion of sodium.
These data provide a target for new therapies that may improve cardiovascular and renal excretory function. This may help treat multiple disease states, such as salt-sensitive hypertension and congestive heart failure caused by elevated sodium intake.
This research was funded by the American Heart Association (AHA) and the National Heart Lung and Blood Institute (NHLBI)
Boston University, Veterans Affairs Boston Healthcare System Study Shows First Case Series of Chronic Traumatic Encephalopathy in Blast-Exposed Military Service Personnel and Mechanism of Injury in Blast Neurotrauma
Contact: Gina DiGravio, 617-638-8480, email@example.com
(Boston) – Investigators from Boston University (BU) and the Veterans Affairs Boston Healthcare System have shown evidence of chronic traumatic encephalopathy (CTE) in brain tissue from blast-exposed military service personnel. Laboratory experiments conducted by the investigators demonstrated that exposure to a single blast equivalent to a typical improvised explosive device (IED) results in CTE and long-term brain impairments that accompany the disease. They also found that the blast wind, not the shock wave, from the IED blast leads to traumatic brain injury (TBI) and long-term consequences, including CTE.
This research, which represents the first case series of postmortem brains from U.S. military personnel who were exposed to a blast and/or a concussive injury, will be published online May 16 by Science Translational Medicine.
Lee Goldstein, MD, PhD, associate professor at Boston University School of Medicine (BUSM) and Boston University College of Engineering, and Ann McKee, MD, professor at BUSM and director of the Neuropathology Service for VA New England Healthcare System, led this international collaborative study and are the senior co-authors.
CTE, which can only be diagnosed postmortem, is a progressive neurodegenerative brain disorder that has been reported in athletes with multiple concussions or subconcussive injuries. In early stages, CTE is characterized by the presence of abnormal deposits of a protein called tau in the form of neurofibrillary tangles, glial tangles and neuropil threads throughout the brain. These tau lesions eventually lead to brain cell death. CTE has clinical features in common with TBI, including psychiatric symptoms and long-term cognitive disability involving memory and learning deficits. TBI can impact military personnel exposed to an explosive blast and may affect approximately 20 percent of the 2.3 million servicemen and women deployed since 2001.
In this study, investigators performed comprehensive neuropathological analyses on brain tissue from four military service personnel with known blast exposure and/or concussive injury. They compared these results with brain tissue samples from three young amateur American football players and a professional wrestler, all of whom had a history of repetitive concussive injury, and four samples from comparably-aged normal controls with no history of blast exposure, concussive injury or neurological disease.
The investigators found that CTE neuropathology in the brains of blast-exposed military veterans was similar to that found in young athletes with repetitive concussion and consistent with what has previously been observed in brain samples from other athletes with a history of repetitive concussive injury.
“Our results showed that the neuropathology from blast exposure, concussive injury, or both were virtually indistinguishable from those with a history of repeat concussive injury,” said McKee, who is the director of the Brain Banks for BU’s Alzheimer’s Disease Center and the Center for the Study of Traumatic Encephalopathy, which are based at the Bedford VA Medical Center. McKee said that these findings indicate that TBI caused by different factors may trigger similar disease pathways in the brain.
“The neuropsychiatric symptoms of CTE that have previously been associated with athletes diagnosed with CTE could also be attributed to military personnel who were exposed to blast,” said Goldstein, who also is affiliated with the BU Photonics Center and served as the study’s lead author.
To examine the impact of a single blast exposure, the investigators collaborated with leading experts in blast physics, experimental pathology and neurophysiology at Boston University, VA Boston Healthcare System, White River Junction VA Medical Center, New York Medical College, Fraunhofer Center for Manufacturing Innovation, University of Massachusetts Lowell, Lawrence Livermore National Laboratory, Massachusetts General Hospital and the University of Oxford. The team’s experimental data showed that one blast comparable to that experienced by military service personnel in the field resulted in both neuropathological and behavioral evidence of CTE. Surprisingly, the long-term impairments in brain function, including impaired learning and memory, were observed just two weeks after exposure to a single blast.
The blast wind from an IED can reach a velocity of up to 330 miles per hour, which is greater than the largest wind gust ever recorded on earth. “The force of the blast wind causes the head to move so forcefully that it can result in damage to the brain,” said Goldstein.
Based on the results, the investigators went a step further and explored how they could prevent the brain injury. They demonstrated that immobilizing the head during a blast exposure prevented the learning and memory deficits associated with CTE that occurred when the head was not immobilized.
“Our study provides compelling evidence that blast TBI and CTE are structural brain disorders that can emerge as a result of brain injury on the battlefield or playing field,” added Goldstein. “Now that we have identified the mechanism responsible for CTE, we can work on developing ways to prevent it so that we can protect athletes and our military service personnel.”
The study results provide a pathway for the development of novel diagnostic strategies for blast-related brain trauma, as well as to treat and rehabilitate those who have been exposed to blast and/or a concussive injury.