scholarly journals Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1650
Author(s):  
Pei-Wen Cheng ◽  
Yi-Chung Wu ◽  
Tzyy-Yue Wong ◽  
Gwo-Ching Sun ◽  
Ching-Jiunn Tseng
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxidative Dna Damage ◽  
Glycogen Synthase ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Mechanical Injury ◽  
Public Health Burden ◽  
Increased Risk ◽  
Gsk 3Β

Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)S9/p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3βS9 was directly bound to p-TauS396. In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect.

scholarly journals Traumatic brain injury as a risk factor for dementia

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
E Mezzalira ◽  
B Stopa ◽  
A Khawaja ◽  
S Izzy ◽  
W Gormley
Keyword(s):  
Public Health ◽  
Traumatic Brain Injury ◽  
Risk Factor ◽  
Brain Injury ◽  
The United States ◽  
Age Group ◽  
Global Public Health ◽  
Public Health Burden ◽  
Increased Risk

Abstract Introduction The Centers for Disease Control and Prevention (CDC) reports that there were 2.87 million cases of traumatic brain injury (TBI) in the United States in 2014, 69 million worldwide. Some studies suggest a connection between TBI and increased risk of dementia, but it remains unclear whether the risk increases with age and TBI severity. Given our aging population, it is essential to better characterize the link between TBI and dementia. Methods We conducted a retrospective cohort study of two major academic medical centers for years 2000-2015. We identified all patients with TBI, aged 45 and older. Variables included age, TBI severity, pre-existing dementia, dementia diagnosed after TBI, years to dementia, and follow-up time. TBI severity was determined by head/neck AIS score, using ICD-PIC software. Mild TBI was defined as AIS 0-2, and Moderate/Severe as AIS 3-6. Analysis was done in R.v.3.0.1 software. Results Overall, there were 14,199 patients with TBI, of which 9,938 (70%) were mild and 4,261 (30%) were moderate/severe. Mean age was 70.5 (±14.0). There were 1,422 cases (10%) of pre-existing dementia, and 850 (6%) cases of dementia diagnosed after TBI. The mean follow-up time was 1,129 (±1,474) days. The 75-84 age group had the highest incidence of TBI (28%). When compared by age group and TBI severity, the proportion of moderate/severe TBI increased with increasing age. The proportion of pre-existing dementia increased with age, as expected. Notably, there is increased incidence of dementia after TBI in patients aged 65 and older (7-10%, p < 0.001). There was no observed effect of TBI severity on the risk of dementia after TBI. Conclusions Our results indicate that TBI is a risk factor for the development of dementia, especially in patients aged 65 and older. Given the global public health burden of these two diseases it is critical to develop effective TBI primary prevention strategies. Key messages TBI is a risk factor for the development of dementia. Need for public health measures to mitigate the risk of TBI in the patient population 65 and older.

scholarly journals Traumatic Brain Injury and Dementia in Medicare Population: Differences in Risk Between Veterans and Non-Veterans

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 850-851
Author(s):  
Arseniy Yashkin
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Senile Dementia ◽  
Strong Predictor ◽  
Community Dwelling ◽  
Risk Scores ◽  
Increased Risk ◽  
Co Morbidity

Abstract The aim of this study was to assess differences in the effect of traumatic brain injury (TBI) on the onset of Alzheimer’s disease (AD) and other dementias between veteran and non-veteran respondents of the Health and Retirement Study as well as to measure the sensitivity of these differences to the introduction of controls for groups of demographic, medical co-morbidity and polygenic risk scores reflecting AD hallmarks. Using the Fine-Gray proportional hazards model we found that TBI was a strong predictor of dementia in community dwelling residents age 65+: for AD associated risk was 181% [Hazard Ratio (HR): 2.81; CI:2.05-3.86] sample-wide and 142% [HR: 2.42; CI:1.31-2.46] in veteran males. Effect magnitude decreased with the addition of risk-related control variables but remained associated with significantly increased risk. Large differences in risk were observed between veteran and non-veteran males for AD, vascular dementia, senile dementia, and dementia with Lewy Bodies

scholarly journals Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?

2010 ◽  
Vol 11 (5) ◽  
pp. 361-370 ◽  
Author(s):  
Victoria E. Johnson ◽  
William Stewart ◽  
Douglas H. Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Amyloid Β

scholarly journals Sport-related concussions

2014 ◽  
Vol 8 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Jéssica Natuline Ianof ◽  
Fabio Rios Freire ◽  
Vanessa Tomé Gonçalves Calado ◽  
Juliana Rhein Lacerda ◽  
Fernanda Coelho ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Changes ◽  
American Football ◽  
Health Concern ◽  
Public Health Concern ◽  
Increased Risk ◽  
High Prevalence ◽  
Biomechanical Forces ◽  
The Brain

ABSTRACT Traumatic brain injury (TBI) is a major cause of lifelong disability and death worldwide. Sport-related traumatic brain injury is an important public health concern. The purpose of this review was to highlight the importance of sport-related concussions. Concussion refers to a transient alteration in consciousness induced by external biomechanical forces transmitted directly or indirectly to the brain. It is a common, although most likely underreported, condition. Contact sports such as American football, rugby, soccer, boxing, basketball and hockey are associated with a relatively high prevalence of concussion. Various factors may be associated with a greater risk of sport-related concussion, such as age, sex, sport played, level of sport played and equipment used. Physical complaints (headache, fatigue, dizziness), behavioral changes (depression, anxiety, irritability) and cognitive impairment are very common after a concussion. The risk of premature return to activities includes the prolongation of post-concussive symptoms and increased risk of concussion recurrence.

scholarly journals Traumatic brain injury among female veterans: a review of sex differences in military neurosurgery

2018 ◽  
Vol 45 (6) ◽  
pp. E16 ◽  
Author(s):  
Lily H. Kim ◽  
Jennifer L. Quon ◽  
Felicia W. Sun ◽  
Kristen M. Wortman ◽  
Maheen M. Adamson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Sex Differences ◽  
Brain Injury ◽  
Mortality Data ◽  
Female Veterans ◽  
Female Representation ◽  
Social Challenges ◽  
Increased Risk ◽  
The Face ◽  
The Impact

The impact of traumatic brain injury (TBI) has been demonstrated in various studies with respect to prevalence, morbidity, and mortality data. Many of the patients burdened with long-term sequelae of TBI are veterans. Although fewer in number, female veterans with TBI have been suggested to suffer from unique physical, mental, and social challenges. However, there remains a significant knowledge gap in the sex differences in TBI. Increased female representation in the military heralds an increased risk of TBI for female soldiers, and medical professionals must be prepared to address the unique health challenges in the face of changing demographics among the veteran TBI population. In this review, the authors aimed to present the current understanding of sex differences in TBI in the veteran population and suggest directions for future investigations.

scholarly journals Traumatic Brain Injury and Risk of Dementia and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Dongqing Gu ◽  
Shan Ou ◽  
Guodong Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Subsequent Development ◽  
Medical Monitoring ◽  
Increased Risk

Introduction: Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer’s disease (AD) but reported inconsistent results. We aim to determine the association between TBI and subsequent occurrence of dementia and AD. Methods: We performed a systematic search in PubMed and Web of Science for studies that quantitatively investigated the association between TBI and risk of dementia and AD and were published on or before September 21, 2021. A random-effect model was used to combine the estimates. Results: Twenty-five eligible articles were included in this meta-analysis. The results suggested that TBI was associated with an increased risk of dementia (pooled odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.53 - 2.14). However, no association was observed between TBI and Alzheimer’s disease (pooled OR = 1.02, 95% CI = 0.91 - 1.15). In the subgroup analysis, TBI with loss of consciousness was not associated with risk of dementia (pooled OR = 0.96, 95% CI = 0.84 - 1.09). Besides, Asian ethnicity, male gender, and mean age of the participants less than 65 were associated with a higher risk of dementia. Conclusion: Our study suggests an increased risk of dementia among individuals with TBI, highlighting the need for more intensive medical monitoring and health education in individuals with TBI. Biological mechanisms linking TBI and the development of dementia are needed in future studies.

scholarly journals A Neprilysin Polymorphism and Amyloid-β Plaques after Traumatic Brain Injury

2009 ◽  
Vol 26 (8) ◽  
pp. 1197-1202 ◽  
Author(s):  
Victoria E. Johnson ◽  
William Stewart ◽  
David I. Graham ◽  
Janice E. Stewart ◽  
Amy H. Praestgaard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Amyloid Β

scholarly journals CNS disease-related protein variants as blood-based biomarkers in traumatic brain injury

Neurology ◽  
2018 ◽  
Vol 91 (15) ◽  
pp. 702-709 ◽  
Author(s):  
Stephanie M. Williams ◽  
Carrie Peltz ◽  
Kristine Yaffe ◽  
Philip Schulz ◽  
Michael R. Sierks
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Cross Sectional Study ◽  
Single Chain ◽  
Characteristic Analysis ◽  
Cross Sectional ◽  
Increased Risk ◽  
Elisa Format ◽  
Protein Variants

ObjectiveTo utilize a panel of 11 single chain variable fragments (scFvs) that selectively bind disease-related variants of TAR DNA-binding protein (TDP)-43, β-amyloid, tau, and α-synuclein to assess damage following traumatic brain injury (TBI), and determine if the presence of protein variants could account for the increased risk of various neurodegenerative diseases following TBI.MethodsWe utilized the panel of 11 scFvs in a sensitive ELISA format to analyze sera from 43 older veterans, 25 who had experienced at least 1 TBI incident during their lifetime (∼29.4 years after TBI), and 18 controls who did not incur TBI, in a cross-sectional study.ResultsEach of the 11 scFvs individually could significantly distinguish between TBI and control samples, though they did not detect each TBI sample. Comparing the levels of all 11 variants, all 25 TBI cases displayed higher reactivity compared to the controls and receiver operating characteristic analysis revealed 100% sensitivity and specificity. Higher total protein variants levels correlated with TBI severity and with loss of consciousness. Oligomeric tau levels distinguished between single and multiple TBI incidents. While all TBI cases were readily selected with the panel, the binding pattern varied from patient to patient, suggesting subgroups that are at increased risk for different neurodegenerative diseases.ConclusionThe panel of protein variants-specific scFvs can be used to identify blood-based biomarkers indicative of TBI even 20 years or more after the initial TBI. Being able to identify subgroups of biomarker profiles allows for the possibility of individually targeted treatments.

Association of Military Employment With Late-Life Cognitive Decline and Dementia: A Population-Based Prospective Cohort Study

2021 ◽  
Author(s):  
Melinda C Power ◽  
Alia E Murphy ◽  
Kan Z Gianattasio ◽  
Y i Zhang ◽  
Rod L Walker ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Cognitive Decline ◽  
Late Life ◽  
Cognitive Change ◽  
Effect Modification ◽  
Sensitivity Analyses ◽  
Loss Of Consciousness ◽  
Increased Risk

ABSTRACT Introduction As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear. Materials and Methods We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC. Results Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): −0.042 (−0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer’s disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness. Conclusions Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults.

Amyloid-β Protein and Neuroglobin Protein as Biomarkers on Brainstem Following Traumatic Brain Injury in Rats

2020 ◽  
Author(s):  
Wenhe Li ◽  
Haijun Zhu ◽  
Yue Liang ◽  
Fang Tong ◽  
Yiwu Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Immunofluorescence Assay ◽  
Amyloid Β Protein ◽  
Sprague Dawley ◽  
Specific Expression ◽  
Western Blot Assay ◽  
Weight Drop

Abstract Background: Biomarkers play an important role in accurate diagnosis of traumatic brain injury (TBI). Due to the complexity and diversity of TBI, it is likely that a single biomarker will not be used for exactly diagnose. Amyloid-beta (Aβ) protein is generated by sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase, which may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain as damage factor of TBI. Its use in diagnosis for TBI is becoming more widespread. Neuroglobin (NGB) protein is great potential to diminish neuronal damage. Most epidemiological evidence suggested that Aβ and NGB may be used as biomarkers on brainstem (BS) following TBI. The aim of this study was to investigate the trend of Aβ and NGB on BS of rats with TBI and to analyze comprehensively them as potential biomarkers. Methods: Adult male Sprague-Dawley rats were subjected to the modified weight-drop model of closed TBI. Biologic behavior observation, histopathological assessments and western blot assay were performed. Aβ and NGB expression indicated temporal changes in BS after TBI. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed.Results: The results of Aβ enable us to speculate that the time points of 3 h, 6 h and 12 h may be crucial points for the diagnosis of TBI. NGB expression in the injured had obvious difference versus the control, the points of 1 h and 3 h were apparently higher than the control, and the groups of 12 h and 48 h were two peaks in the present study. Furthermore, the immunofluorescence assay results supported that Aβ and NGB co-localization in the neuros of BS, and the NGB specific expression in the BS of neurons.Conclusions: Therefore, the expression and change rules of Aβ and NBG in the BS may provide an important foundation for the diagnosis of TBI, damage assessment and therapeutic intervention.

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