Traumatic Brain Injury, Microglia, and Beta Amyloid

Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (Aβ). Data from both AD and TBI studies suggest that microglia play a central role in Aβ accumulation after TBI. This paper focuses on the current research on the role of microglia response to Aβ after TBI

Multiple prior concussions are associated with symptoms in high school athletes

Objectives: The purpose of this study was to evaluate the association of prior concussion on baseline computerized neurocognitive testing in a large cohort of high school athletes. Methods: This is a retrospective cohort study of student athletes from 49 Maine High Schools in 2010 who underwent baseline computerized neurocognitive evaluation with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®). As part of the ImPACT®, subjects reported a prior history of concussion as well as demographic information and a symptom questionnaire. We used linear regression to evaluate the association of prior concussion with baseline: (1) ImPACT® composite scores; and (2) symptom scores. Results: Six thousand seventy-five subjects were included in the study, of whom 57% were boys. The majority of student athletes (85.3%) reported no prior history of concussion while 4.6% reported having sustained two or more prior concussions. On simple linear regression, increasing number of concussions was related to worse performance in verbal memory (P = 0.039) and greater symptoms scores (P < 0.001). On multivariate modeling, only the association with baseline symptoms remained (P < 0.001). Other factors associated with baseline symptom reporting in the multivariate model included mental health history, headache/migraine history, gender, developmental and/or learning problems, and number of prior concussions. Interpretation In this large-scale, retrospective survey study, history of multiple prior concussions was associated with higher symptom burden but not baseline computerized neurocognitive testing. The association between baseline symptom reporting and clinical and demographic factors was greater than the association with a history of multiple concussions

Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function

Background: Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month. Methods: Pregnant rats underwent laparotomy on embryonic day 18 and transient systemic HI (TSHI) and/or intra-amniotic LPS injection. Shams received laparotomy and anesthesia only. Pups were born at term. Immunohistochemistry with stereological estimates was performed to assess regional glial loads, and western blots were performed for protein expression. Erythropoietin ligand and receptor levels were quantified using quantitative PCR. Digigait analysis detected gait deficits. Statistical analysis was performed with one-way analysis of variance and post-hoc Bonferonni correction. Results: Microglial and astroglial immunolabeling are elevated in TSHI + LPS fimbria at postnatal day 2 compared to sham (both P < 0.03). At postnatal day 15, myelin basic protein expression is reduced by 31% in TSHI + LPS pups compared to shams (P < 0.05). By postnatal day 28, white matter injury shifts from the acute injury pattern to a chronic injury pattern in TSHI pups only. Both myelin basic protein expression (P < 0.01) and the phosphoneurofilament/neurofilament ratio, a marker of axonal dysfunction, are reduced in postnatal day 28 TSHI pups (P < 0.001). Erythropoietin ligand to receptor ratios differ between brains exposed to TSHI and LPS. Gait analyses reveal that all groups (TSHI, LPS and TSHI + LPS) are ataxic with deficits in stride, paw placement, gait consistency and coordination (all P < 0.001). Conclusions: Prenatal TSHI and TSHI + LPS lead to different patterns of injury with respect to myelination, axon integrity and gait deficits. Dual injury leads to acute alterations in glial response and cellular inflammation, while TSHI alone causes more prominent chronic white matter and axonal injury. Both injuries cause significant gait deficits. Further study will contribute to stratification of injury mechanisms in preterm infants, and guide the use of promising therapeutic interventions

Examining racial and ethnic disparities in adult emergency department patient visits for concussion in the United States

Background Racial and ethnic differences in emergency department (ED) visits have been reported among adolescent patients but are unsubstantiated among adults. Therefore, our purpose in this study was to examine the relationship between race/ethnicity and adult ED visits for concussions, their injury mechanisms, and computed tomography (CT) scan use among a nationally representative sample. Methods We used the National Hospital Ambulatory Medical Care Survey database from 2010–2015 to examine 63,725 adult (20–45 years old) patient visits, representing an estimated 310.6 million visits presented to EDs. Of these visits, 884 (4.5 million national estimate) were diagnosed with a concussion. Visit records detailed patient information (age, sex, race/ethnicity, geographic region, primary payment type), ED visit diagnoses, injury mechanism (sport, motor vehicle, fall, struck by or against, “other”), and head CT scan use. The primary independent variable was race/ethnicity (non-Hispanic Asian, non-Hispanic Black or African American, Hispanic/Latinx, non-Hispanic multiracial or another, and non-Hispanic White). We used multivariable logistic and multinomial regression models with complex survey sampling design weighting to examine the relationship between concussion ED visits, injury mechanisms, and CT scan use separately by race/ethnicity while accounting for covariates. Results There were no associations between race/ethnicity and concussion diagnosis among adult ED visits after accounting for covariates. Relative to sports-related injuries, non-Hispanic Black or African American patient visits were associated with a motor vehicle (OR = 2.69, 95% CI: 1.06–6.86) and “other” injury mechanism (OR = 4.58, 95% CI: 1.34–15.69) compared to non-Hispanic White patients. Relative to sports-related injuries, non-Hispanic Asian, multiracial, or patients of another race had decreased odds of falls (OR = 0.20, 95% CI: 0.04–0.91) and “other” injuries (OR = 0.09, 95% CI: 0.01–0.55) compared to non-Hispanic White patients. The odds of a CT scan being performed were significantly lower among Hispanic/Latinx patient visits relative to non-Hispanic White patients (OR = 0.52, 95% CI: 0.30–0.91), while no other race/ethnicity comparisons differed. Conclusion Our findings indicate that the overarching concussion ED visit likelihood may not differ by race/ethnicity in adults, but the underlying mechanism causing the concussion and receiving a CT scan demonstrates considerable differences. Prospective future research is warranted to comprehensively understand and intervene in the complex, multi-level race/ethnicity relationships related to concussion health care to ensure equitable patient treatment

Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and asso- ciated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment

Diagnosing Mild Traumatic Brain Injury Using Saliva RNA Compared to Cognitive and Balance Testing

BACKGROUND: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance. METHODS: This case‐control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4‐7, 8‐14, 15‐30, and 31‐60 days post‐mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi‐interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. RESULTS: A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross‐validated area under the curve (AUC) of .857 in the training set (95% CI, .816‐.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post‐Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross‐validated AUC of .835 (95% CI, .782‐.880) and .853 (95% CI, .803‐.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845‐.925) as symptom burden and four ncRNAs (.932; 95% CI, .890‐.965). CONCLUSION: Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI

Carbon Monoxide Exposure in Youth Ice Hockey

OBJECTIVE: To examine the effect of ice resurfacer type on carboxyhemoglobin levels in youth hockey players. We hypothesized that players in arenas with electric resurfacers would have normal, stable carboxyhemoglobin levels during games, whereas those in arenas with internal combustion engine (IC) resurfacers would have an increase in carboxyhemoglobin levels. DESIGN: Prospective cohort study. SETTING: Enclosed ice arenas in the northeastern United States. PARTICIPANTS: Convenience sample of players aged 8 to 18 years old in 16 games at different arenas. Eight arenas (37 players) used an IC ice resurfacer and 8 arenas (36 players) an electric resurfacer. INTERVENTIONS: Carboxyhemoglobin levels (SpCO) were measured using a pulse CO-oximeter before and after the game. Arena air was tested for carbon monoxide (CO) using a metered gas detector. Players completed symptom questionnaires. MAIN OUTCOME MEASURES: The change in SpCO from pregame to postgame was compared between players at arenas with electric versus IC resurfacers. RESULTS: Carbon monoxide was present at 6 of 8 arenas using IC resurfacers, levels ranged from 4 to 42 parts per million. Carbon monoxide was not found at arenas with electric resurfacers. Players at arenas with IC resurfacers had higher median pregame SpCO levels compared with those at electric arenas (4.3% vs 1%, P \u3c 0.01). Players in the IC group also had a significant increase in their SpCO level during a hockey game compared with those in the electric group (2.8% vs 1%, P = 0.01). There were no significant differences in symptom scores. CONCLUSIONS: Players at arenas operating IC resurfacers had significantly higher SpCO levels. CLINICAL RELEVANCE: Youth hockey players in arenas with IC resurfacers have an increase in carboxyhemoglobin during games and have elevated baseline carboxyhemoglobin levels compared with players at arenas with electric resurfacers. Electric resurfacers decrease the risk of CO exposure

Initial symptom burden predicts duration of symptoms after concussion

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 1991Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 1991Güç sisteminde çalışan mühendisler için bilgisayar ile analiz önemli bir araç olarak kullanılmak tadır. Güç sistemindeki bozulmalar ve sorunların değerlendirilmesinde, güç sistemlerinin benzetişimi ve modellenmesi gerekli olur. Devredeki bozulmalar çok kez sistemdeki Uç faz akım ve gerilim dalga çeki 11 erindeki bozulmalar olarak ortaya çıkar. Uluslar arası düzeyde çalışma konusu olan bir bozulma şekli ise, günümüz modern güç sistemlerini olumsuz olarak etkileyen, " Güç Sistemi Harmonikleri " dir. Bu konuda çeşitli ülkelerde belirlenmiş olan uluslar arası sınır değerler Tablo 1.1* de sunulmuştur. Güç sistemindeki AA harmonikleri, sistemi artan bir oranda etkilemekte, tesislerde zarara ve güç kesintilerine neden olmaktadır. Her ne kadar süzgeç devreleri yaygın bir şekilde kullanılmaya başlanmışsada süzgeci eme tesislerinin toplam maliyeti artırması. Statik Var sistemi yada Ark Fırını gibi tesislerde kullanılan süzgeçlerde, maliyet optimizasyonunu gerekli hale getirmiştir. Sorunun en önemli kısmının ise güç sistemindeki harmoni ki er in kuramsal olarak hesaplanmasında bulunduğu görülmektedir. Bu çalışma, zamanla değişen yüklerin ve bunların meydana getirdiği harmoni ki er in incelenmesi amacı ile geliştirilen, bilgisayarlı ölçüm ve benzetişim yöntemlerini içermektedir. Benzetişim sonunda hesaplanan kuramsal sonuçlarla ölçüm sonuçları karşılaştırılmıştır. Ölçüm amacı ile gidilen Mahmut Bey'de Orpaş Ark Fırını Tesislerinde bazı datalar alınmıştır. Hesaplamalarda zaman domeni ve " Hızİı Fourier Dönüşümü " CFFTD bağıntıları kullanılmıştır.Computer analysis is an important tool for power system engineers. The simulation and modeling of the various power system networks is necessary to help evalute problems and disturbances through practical solutions. An increase in the number, and influences, of nonlinear harmonic producing devices connected to the power system has increased significantly during the past decade. Industrial installations utilizing modern arc furnace technology, power electronic systems have been studied in this thesis. These applications cause non- linearities to appear at the AC terminals of the high power transformers located at the power network sub stations. Due to the duty cycles and load profiles of these applications, the voltage and current wave forms are becoming distorted and more nonsinusoi- dal. Through this thesis work a versatile and high speed computerized measrementand simulation technique has been formulated and implemented. Its capabilities demonstrated for the data acquisition of time-varying, nonlinear loads. A simulation technique based upon frequency and time domain modelling of the network components and harmonik producing devices has been developed for this thesis study. Voltage and Current AC harmonics are penetrating todays power systems at an increaseing rate. The propagation of AC harmonics throughout the power networks produce undesired voltage voltage distrubances, causing damage to equipment and power outages. Computerized measurement and simulation techniquis for the study of power system harmonics are becoming very important analysis tools. Both the suppliers and consumers of electrical energy must improve their understanding of the causes and utilize better analytical techniques for the prediction and solution of harmonic problems. The power system network is primarily described and studied as a complex circuit with linear elements and sources with sinusoidal functions. Usual y the performance conditions of the system define the applicable network model. - vi - The study of harmonic penetration into the power system network, which involves computer analysis and simulation techniques, is one of the main objectives of this work. The prediction and estimation of voltage harmonics, propagation of current harmonics, and waveform distortionCs!» caused by the various categories of nonlinear loads will be addressed. In addition, a new analytical approach and measurement results will be presented. It is the objective of this study to develop alternate analytical and measurement approaches for the determination of AC harmonic penetration into the power system network. As mentioned earlier, distortions in the power system are primarily due to the nonlinear V-I characteristics at the terminals of elements, loads, and sources in the network. Nonlinear loads are classified as devices which produce nonsinusoidal currents at the input side of its terminals. These types of devices are : * Power Electronic switching devices Devi c e Con ver si on Rectifier AC » DC DC Linked Inverter AC » DC - ? AC Cycl ©converter and AC choppers AC ? AC * Magnetic circuits acting in their saturation region > transformers, motors * Arcing elements and systems > mechanical rectifiers C commutator -type motor sD > Arc Furnaces - vii - > gas-type fl orescent lighting systems. Since nonlinear loads and sources are the primary causes for harmonics in the power system, further explanations and accepted interpretations have been identified. The V-I characteristics of passive elements Crezistors, inductors, capasitors? define the classifica tion of whether or not these are linear or nonlinear components in the network. Nonlinear components which have nonlinear V-I characteristics are identified according to the distortions upon the input AC voltage and current waveforms. The following cases that one may come across are listed. Input Waveforms Loads, El ements Harmonic Source Case I : The incoming input waveforms are sinusoidal and later transfer into a non-sinusoidal waveform due to the 1 oads. el ements, or devices connection combination. Case II: The incoming input waveformCs^ are originally non-si nusoi dal. The propagation of harmonic signals throughout a network are dependent upon how the admittances and impedances are effected by the harmonic currents flowing. The equivalent, lumped parameter circuit representation of a power system, therefore, can be modelled by using the YBUS Matrix or ZBUS Matrix approaches. The advantages and/or disadvantages between these two models are not addressed by this research effort. The utilization and., benefits seen by using the YBUS Matrix approach for modelling the systems components and predicting voltage - viii - and current harmonic distortion levels are documented here. Frequency-domain harmonic studies require that the components be modelled as a function of the fundamental frequency and variations in the components characteristics based upon harmonic orders. The YBUS Matrix is used for determining the network admittance values. The constr action of the YBUS and formation of the injected harmonic current vector values form the algorithm to determine the voltage harmonics in the network. Presented here, since -1 C1D bus I I bus I I bus I both balanced and unbalanced case conditions can be analyzed. In the balanced case, the Ybus matrix is simply and the I bus vector is mostly zeroes except at the bus locations where harmonic disturbances are specified. In Chapter 1, harmonic sources, nonliner loads are presented. Chapter 2 included harmonic resonance conditions C serial and parallel resonances). Chapter 3 deals with the modelling and simulation approaches used in this study. Power system component harmonic models, and several types of nonlinear load models have been described. Chapter 4 is mainly concerned with the harmonic measurement system specifications and the requirements considered to be important aspects for taking harmonic measurements of time-varying loads. In Chapter 5, two case studies are presented. An Arc Furnace CORPAŞ A. S. 3 in Istanbul. V-I waveforms are masured and FFT Analysis are studied. Figure S. 1 shows current waveform and FFT Analysis. Figure S. 2 shows voltage waveform and FFT Analysis. The second case studies PETLAS Rubber factory in Kırşehir. To estimate harmonic numder and magnetuid, we modelled the system. On the other hand, for V-I waveforms are data aquired and FFT Analysis are made.Yüksek LisansM.Sc