Browsing by Subject "Traumatic brain injury"
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Item Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury(Elsevier, 2016-09-06) Shee, Kevin; Lucas, Alexandra; Flashman, Laura A.; Nho, Kwangsik; Tsongalis, Gregory J.; McDonald, Brenna C.; Saykin, Andrew J.; McAllister, Thomas W.; Rhodes, C. Harker; Psychiatry, School of MedicineProblems with attention and short-term learning and memory are commonly reported after mild traumatic brain injury (mTBI). Due to the known relationships between α-synuclein (SNCA), dopaminergic transmission, and neurologic deficits, we hypothesized that SNCA polymorphisms might be associated with cognitive outcome after mTBI. A cohort of 91 mTBI patients one month after injury and 86 healthy controls completed a series of cognitive tests assessing baseline intellectual function, attentional function, and memory, and was genotyped at 13 common single nucleotide polymorphisms (SNPs) in the SNCA gene. Significant differences in two memory measures (p = 0.001 and 0.002), but not baseline intellectual function or attentional function tasks, were found between the mTBI group and controls. A highly significant protective association between memory performance and SNCA promoter SNP rs1372525 was observed in the mTBI patients (p = 0.006 and 0.029 for the long and short delay conditions of the California Verbal Learning Tests, respectively), where the presence of at least one copy of the A (minor) allele was protective after mTBI. These results may help elucidate the pathophysiology of cognitive alterations after mTBI, and thus warrant further investigation.Item Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease(Society for Neuroscience, 2002-12) Hartman, Richard E.; Laurer, Helmut; Longhi, Luca; Bales, Kelly R.; Paul, Steven M.; McIntosh, Tracy K.; Holtzman, David M.; Pharmacology and Toxicology, School of MedicineThe epsilon4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). These factors may act synergistically, in that APOE4+ individuals are more likely to develop dementia after TBI. Because the mechanism underlying these effects is unclear, we questioned whether APOE4 and TBI interact either through effects on amyloid-beta (Abeta) or by enhancing cell death/tissue injury. We assessed the effects of TBI in PDAPP mice (transgenic mice that develop AD-like pathology) expressing human APOE3 (PDAPP:E3), human APOE4 (PDAPP:E4), or no APOE (PDAPP:E-/-). Mice were subjected to a unilateral cortical impact injury at 9-10 months of age and allowed to survive for 3 months. Abeta load, hippocampal/cortical volumes, and hippocampal CA3 cell loss were quantified using stereological methods. All of the groups contained mice with Abeta-immunoreactive deposits (56% PDAPP:E4, 20% PDAPP:E3, 75% PDAPP:E-/-), but thioflavine-S-positive Abeta (amyloid) was present only in the molecular layer of the dentate gyrus in the PDAPP:E4 mice (44%). In contrast, our previous studies showed that in the absence of TBI, PDAPP:E3 and PDAPP:E4 mice have little to no Abeta deposition at this age. After TBI, all of the Abeta deposits present in PDAPP:E3 and PDAPP:E-/- mice were diffuse plaques. In contrast to the effect of APOE4 on amyloid, PDAPP:E3, PDAPP:E4, and PDAPP:E-/- mice did not differ in the amount of brain tissue or cell loss. These data support the hypothesis that APOE4 influences the neurodegenerative cascade after TBI via an effect on Abeta.Item Association between concussion and mental health in former collegiate athletes(Springer, 2014-12) Kerr, Zachary Y.; Evenson, Kelly R.; Rosamond, Wayne D.; Mihalik, Jason P.; Guskiewicz, Kevin M.; Marshall, Stephen W.; Department of Social and Behavioral Sciences, Richard M. Fairbanks School of Public HealthBACKGROUND: The existing research on the association between concussion and mental health outcomes is largely limited to former professional athletes. This cross-sectional study estimated the association between recurrent concussion and depression, impulsivity, and aggression in former collegiate athletes. METHODS: Former collegiate athletes who played between 1987-2012 at a Division I university completed an online questionnaire. The main exposure, total number of self-recalled concussions (sport-related and non-sport-related), were categorized as: zero (referent), one, two, or three or more concussions. The main outcomes were the depression module of The Patient Health Questionnaire (PHQ-9), the Short Form of the Barratt Impulsiveness scale (BIS15); and the 12-item Short Form of the Buss-Perry Aggression Questionnaire (BPAQ-SF). Depression was categorized into a binomial severity classification that differentiated between no or mild depression (PHQ-9 scores <10) and moderate to severe depression (PHQ-9 scores ≥10). Impulsivity and aggression were kept as continuous outcomes. Binomial regression estimated adjusted prevalence ratios (PR). Linear regression estimated adjusted mean differences (MD). RESULTS: Of the 797 respondents with complete data (21.9% completion rate), 38.8% reported at least one concussion. Controlling for alcohol dependence and family history of depression, the prevalence of moderate to severe depression among former collegiate athletes reporting three or more concussions in total was 2.4 times that of those reporting zero concussions [95% Confidence Interval (CI): 1.0, 5.7]. Controlling for alcohol dependence, family history of anxiety, relationship status, obtaining a post-graduate degree, and playing primary college sport professionally, former collegiate athletes reporting two or more concussions in total had higher mean scores for impulsivity, compared to those reporting no concussions (2 concussions MD = 2.7; 95% CI: 1.2, 4.1; 3+ concussions MD = 1.9; 95% CI: 0.6, 3.2). Controlling for alcohol dependence, sex, and relationship status, former collegiate athletes reporting three or more concussions in total had a higher mean score for aggression, compared to those reporting no concussions (MD = 3.0; 95% CI: 1.4, 4.7). CONCLUSIONS: Our study found an association between former concussion and greater risk of severe depression and higher levels of impulsivity and aggression among former collegiate athletes. Additional prospective studies better addressing causality and ascertaining valid lifetime concussion histories and medical histories are needed.Item Brain Rehabilitation, Advanced Imaging, and Neuroscience (BRAIN): An IUPUI Signature Center Initiative (SCI)(Office of the Vice Chancellor for Research, 2015-04-17) Hammond, Flora; Saykin, Andrew J.; Malec, JamesAbstract The Mission of the Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN) is: to develop and disseminate techniques and methodologies for combining advanced neuroimaging, neurogenetics and other neurophysiological measures with precision behavioral measurement to evaluate novel rehabilitation interventions for people with acquired brain injury. Traumatic and other types of acquired brain injury (ABI) affect millions of U.S. citizens each year, many of whom experience persistent disabilities. Over the past decade there has been a notable rise in research activities to address serious gaps in the knowledge base of ABI, including neuroimaging, outcome measurement, and intervention studies to change function. However, brain injury researchers have not yet established solid links between these research agendas. The BRAIN SCI fills this gap in neuroscience by bringing together an interdisciplinary team of clinical researchers to (1) advance basic science and clinical knowledge to the next level of integration, (2) translate the knowledge gained into clinical care for improved patient outcomes, and (3) use the newly integrated knowledge to drive the leading edge of translational research. BRAIN research includes the Indiana Traumatic Brain Injury Model System, funded by the National Institute for Disability and Rehabilitation Research (NIDRR), the InterFACE Center for the study of emotions and interpersonal interactions after neurologic injury, and 12 externally funded research projects. BRAIN research ranges from development of a neurogenetic respository and advanced neuroimaging studies to determine critical elements in recovery from brain injury to intervention studies to improve recovery to a multi-national study of an intervention for phantom limb pain. BRAIN research is transdisciplinary. Disciplines currently involved in BRAIN research include physiatry, neuropsychology, neuroradiology, rehabilitation science, biomedical engineering, and psychiatry. The Indiana University School of Medicine Neuroscience Center provides a home for BRAIN and supports its interdisciplinary Steering Committee. In addition to partnerships with the Neuroscience Center, the Center for Neuroimaging, and the InterFACE Center, BRAIN collaborates with the Rehabilitation Hospital of Indiana, the Stark Neuroscience Institute, and the School of Health and Rehabilitation Sciences. This presentation will describe BRAIN’s mission, vision, values, strategic plan, organization, partnerships, and ongoing research projects in greater detail.Item Cerebral blood flow in acute concussion: preliminary ASL findings from the NCAA-DoD CARE consortium(Springer, 2019-10-01) Wang, Yang; Nencka, Andrew S.; Meier, Timothy B.; Guskiewicz, Kevin; Mihalik, Jason P.; Alison Brooks, M.; Saykin, Andrew J.; Koch, Kevin M.; Wu, Yu-Chien; Nelson, Lindsay D.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael A.; Radiology and Imaging Sciences, School of MedicineSport-related concussion (SRC) has become a major health problem, affecting millions of athletes each year. Despite the increasing occurrence and prevalence of SRC, its underlying mechanism and recovery course have yet to be fully elucidated. The National Collegiate Athletic Association–Department of Defense Grand Alliance: Concussion Assessment, Research and Education (CARE) Consortium is a large-scale, multisite study of the natural history of concussion across multiple sports. The Advanced Research Core (ARC) of CARE is focused on the advanced biomarker assessment of a reduced subject cohort. This paper reports findings from two ARC sites to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared relative CBF maps assessed in 24 concussed contact sport athletes obtained at 24–48 h after injury to those of a control group of 24 matched contact sport players. Significantly less CBF was detected in several brain regions in concussed athletes, while clinical assessments also indicated clinical symptom and performance impairments in SRC patients. Correlations were found between decreased CBF in acute SRC and clinical assessments, including Balance Error Scoring System total score and Immediate Post-Concussion Assessment and Cognitive Test memory composite and impulse control composite scores, as well as days from injury to asymptomatic. Although using different ASL MRI sequences, our preliminary results from two sites are consistent with previous reports and suggest that advanced ASL MRI methods might be useful for detecting acute neurobiological changes in acute SRC.Item A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium(Biomed Central, 2019-01-14) Van Pelt, Kathryn L.; Allred, Dain; Cameron, Kenneth L.; Campbell, Darren E.; D’Lauro, Christopher J.; He, Xuming; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; Meehan, Sean; O’Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Medicine, School of MedicineBACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention.Item A Compact Blast-Induced Traumatic Brain Injury Model in Mice(Oxford University Press, 2016-02) Wang, Hongxing; Zhang, Yi Ping; Cai, Jun; Shields, Lisa B. E.; Tuchek, Chad A.; Shi, Riyi; Li, Jianan; Shields, Christopher B.; Xu, Xiao-Ming; Neurological Surgery, School of MedicineBlast-induced traumatic brain injury (bTBI) is a common injury on the battlefield and often results in permanent cognitive and neurological abnormalities. We report a novel compact device that creates graded bTBI in mice. The injury severity can be controlled by precise pressures that mimic Friedlander shockwave curves. The mouse head was stabilized with a head fixator, and the body was protected with a metal shield; shockwave durations were 3 to 4 milliseconds. Reflective shockwave peak readings at the position of the mouse head were 12 6 2.6 psi, 50 6 20.3 psi, and 100 6 33.1 psi at 100, 200, and 250 psi predetermined driver chamber pressures, respectively. The bTBIs of 250 psi caused 80% mortality, which decreased to 27% with the metal shield. Brain and lung damage depended on the shockwave duration and amplitude. Cognitive deficits were assessed using the Morris water maze, Y-maze, and open-field tests. Pathological changes in the brain included disruption of the blood-brain barrier, multifocal neuronal and axonal degeneration, and reactive gliosis assessed by Evans Blue dye extravasation, silver and Fluoro-Jade B staining, and glial fibrillary acidic protein immunohistochemistry, respectively. Behavioral and pathological changes were injury severity-dependent. This mouse bTBI model may be useful for investigating injury mechanisms and therapeutic strategies associated with bTBI.Item COMT Val 158 Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury(Elsevier, 2017-01) Winkler, Ethan A.; Yue, John K.; Ferguson, Adam R.; Temkin, Nancy R.; Stein, Murray B.; Barber, Jason; Yuh, Esther L.; Sharma, Sourabh; Satris, Gabriela G.; McAllister, Thomas W.; Rosand, Jonathan; Sorani, Marco D.; Lingsma, Hester F.; Tarapore, Phiroz E.; Burchard, Esteban G.; Hu, Donglei; Eng, Celeste; Wang, Kevin K.W.; Mukherjee, Pratik; Okonkwo, David O.; Diaz-Arrastia, Ramon; Manley, Geoffrey T.; TRACK-TBI Investigators; Psychiatry, School of MedicineMild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met158 allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val158Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.Item COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury(Springer, 2016-01) Winker, Ethan A.; Yue, John K.; McAllister, Thomas W.; Temkin, Nancy R.; Oh, Sam S.; Burchard, Esteban G.; Hu, Donglei; Ferguson, Adam R.; Lingsma, Hester F.; Burke, John F.; Sorani, Marco D.; Rosand, Jonathan; Yuh, Esther L.; Barber, Jason; Tarapore, Phiroz E.; Gardner, Raquel C.; Sharma, Sourabh; Satris, Gabriela G.; Eng, Celeste; Puccio, Ava M.; Wang, Kevin K.W.; Mukherjee, Pratik; Valadka, Alex B.; Okonkwo, David O.; Diaz-Arrastia, Ramon; Manley, Geoffrey T.; Department of Psychiatry, IU School of MedicineMild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI--Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.Registry: ClinicalTrials.gov Identifier NCT01565551.Item Controlled cortical impact model for traumatic brain injury(JoVE, 2014-08-05) Romine, Jennifer; Gao, Xiang; Chen, Jinhui; Department of Neurological Surgery, IU School of MedicineEvery year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.