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Genetics traumatic brain injury

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https://www.readbyqxmd.com/read/28522734/voluntary-control-of-epileptiform-spike-wave-discharges-in-awake-rats
#1
Jeremy A Taylor, Krista M Rodgers, Florencia M Bercum, Carmen J Booth, F Edward Dudek, Daniel S Barth
Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike-wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities and anti-absence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy; PTE). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28502803/gene-co-expression-networks-identify-trem2-and-tyrobp-as-major-hubs-in-human-apoe-expressing-mice-following-traumatic-brain-injury
#2
Emilie L Castranio, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Nicholas F Fitz, Florent Letronne, Jonathan Schug, Radosveta Koldamova, Iliya Lefterov
Traumatic brain injury (TBI) is strongly linked to an increased risk of developing dementia, including chronic traumatic encephalopathy and possibly Alzheimer's disease (AD). APOEε4 allele of human Apolipoprotein E (APOE) gene is the major genetic risk factor for late onset AD and has been associated with chronic traumatic encephalopathy and unfavorable outcome following TBI. To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms...
May 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28485728/adenosine-a2a-receptor-inactivation-alleviates-early-onset-cognitive-dysfunction-after-traumatic-brain-injury-involving-an-inhibition-of-tau-hyperphosphorylation
#3
Z-A Zhao, Y Zhao, Y-L Ning, N Yang, Y Peng, P Li, X-Y Chen, D Liu, H Wang, X Chen, W Bai, J-F Chen, Y-G Zhou
Tau is a microtubule-associated protein, and the oligomeric and hyperphosphorylated forms of tau are increased significantly after neurotrauma and considered important factors in mediating cognitive dysfunction. Blockade of adenosine A2A receptors, either by caffeine or gene knockout (KO), alleviates cognitive dysfunction after traumatic brain injury (TBI). We postulated that A2AR activation exacerbates cognitive impairment via promoting tau hyperphosphorylation. Using a mouse model of moderate controlled cortical impact, we showed that TBI induced hyperphosphorylated tau (p-tau) in the hippocampal dentate gyrus and spatial memory deficiency in the Morris water maze test at 7 days and 4 weeks after TBI...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28482760/association-of-lectin-pathway-protein-levels-and-genetic-variants-early-after-injury-with-outcomes-after-severe-traumatic-brain-injury-a-prospective-cohort-study
#4
Michael Osthoff, Bernhard Walder, Cécile Delhumeau, Marten Trendelenburg, Natacha Turck
The lectin pathway of the complement system has been implicated in secondary ischemic/inflammatory injury after traumatic brain injury (TBI). However, previous experimental studies have yielded conflicting results, and human studies are scarce. In this exploratory study we investigated associations of several lectin pathway proteins early after injury and single-nucleotide polymorphisms (SNP) with outcomes after severe TBI [mortality at 14 days (primary outcome) and consciousness assessed with the Glasgow Coma Scale (GCS) at 14 days, disability assessed with the Glasgow Outcome Scale Extended (GOSE) at 90 days]...
May 8, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28469658/neural-stem-cells-over-expressing-brain-derived-neurotrophic-factor-promote-neuronal-survival-and-cytoskeletal-protein-expression-in-traumatic-brain-injury-sites
#5
Tao Chen, Yan Yu, Liu-Jiu Tang, Li Kong, Cheng-Hong Zhang, Hai-Ying Chu, Liang-Wei Yin, Hai-Ying Ma
Cytoskeletal proteins are involved in neuronal survival. Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury. However, the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear. To examine this, we established a rat model of traumatic brain injury by controlled cortical impact. At 72 hours after injury, 2 × 10(7) cells/mL neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells (3 mL) were injected into the injured cortex...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28413696/prevalence-of-potential-sports-associated-risk-factors-in-swiss-amyotrophic-lateral-sclerosis-patients
#6
Nina Feddermann-Demont, Astrid Junge, Konrad P Weber, Michael Weller, Jiří Dvořák, Alexander A Tarnutzer
OBJECTIVES: Amyotrophic lateral sclerosis (ALS) has been reported to occur with increased incidence amongst physically active people. The role of extrinsic risk factors as physical activity, head trauma and drug/pesticide-exposure in the pathophysiology of ALS and especially in the context of practising sports remains controversial. MATERIALS AND METHODS: We retrospectively studied exposure to extrinsic factors in 92 ALS patients in the presymptomatic stage. Metabolic equivalents (METs) were calculated and the association of physical activity, drug intake, head trauma and participation in specific sports (football [soccer], ice hockey) with age at symptom-onset was evaluated...
April 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28390522/research-frontiers-in-traumatic-brain-injury-defining-the-injury
#7
REVIEW
Andrew J Gardner, Shirley L Shih, Elizabeth V Adamov, Ross D Zafonte
With the continued advancement in technology, such as increasingly sophisticated neuroimaging parameters, and the ongoing development of various scientific fields, like serum and blood biomarkers, genetics, and physiology, traumatic brain injury (TBI) research is a dynamic field of study. TBI remains a significant public health concern and research has continued to grow exponentially over the past decade. This review provides an overview of the frontiers of TBI research, from sports concussion to severe TBI, from acute and subacute injury to long-term/chronic outcomes, from assessment and management to prognosis, specifically examining recent neuroimaging, biomarkers, genetics, and physiologic studies...
May 2017: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/28337122/cerebrospinal-fluid-cortisol-mediates-brain-derived-neurotrophic-factor-relationships-to-mortality-after-severe-tbi-a-prospective-cohort-study
#8
Miranda J Munoz, Raj G Kumar, Byung-Mo Oh, Yvette P Conley, Zhensheng Wang, Michelle D Failla, Amy K Wagner
Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0-6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in "younger patients" (<48 years) and hypothesized BDNF production/secretion capacity with these variants...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28332151/blockade-of-neuroglobin-reduces-protection-of-conditioned-medium-from-human-mesenchymal-stem-cells-in-human-astrocyte-model-t98g-under-a-scratch-assay
#9
Eliana Baez-Jurado, Gina Guio Vega, Gjumrakch Aliev, Vadim V Tarasov, Paula Esquinas, Valentina Echeverria, George E Barreto
Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay...
March 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#10
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
June 1, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28319562/translating-biomarkers-from-research-to-clinical-use-in-pediatric-neurocritical-care-focus-on-traumatic-brain-injury-and-cardiac-arrest
#11
Andrew J Prout, Michael S Wolf, Ericka L Fink
PURPOSE OF REVIEW: Traumatic brain injury (TBI) and cardiac arrest are important causes of morbidity and mortality in children. Improved diagnosis and outcome prognostication using validated biomarkers could allow clinicians to better tailor therapies for optimal efficacy. RECENT FINDINGS: Contemporary investigation has yielded plentiful biomarker candidates of central nervous system (CNS) injury, including macromolecules, genetic, inflammatory, oxidative, and metabolic biomarkers...
June 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28301983/applying-systems-biology-methodology-to-identify-genetic-factors-possibly-associated-with-recovery-after-traumatic-brain-injury
#12
Brad G Kurowski, Amery Treble-Barna, Alexis J Pitzer, Shari L Wade, Lisa J Martin, Ranjit S Chima, Anil Jegga
Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. It is linked with a number of medical, neurological, cognitive, and behavioral sequelae. The influence of genetic factors on the biology and related recovery after TBI is poorly understood. Studies that seek to elucidate the impact of genetic influences on neurorecovery after TBI will lead to better individualization of prognosis and inform development of novel treatments, which are considerably lacking. Current genetic studies related to TBI have focused on specific candidate genes...
May 3, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28284950/naloxone-exacerbates-memory-impairments-and-depressive-like-behavior-after-mild-traumatic-brain-injury-mtbi-in-mice-with-upregulated-opioid-system-activity
#13
Anna Lesniak, Pawel Leszczynski, Magdalena Bujalska-Zadrozny, Chaim G Pick, Mariusz Sacharczuk
The neuroprotective role of the endogenous opioid system in the pathophysiological sequelae of brain injury remains largely ambiguous. Noteworthy, almost no data is available on how its genetically determined activity influences the outcome of mild traumatic brain injury. Thus, the aim of our study was to examine the effect of opioid receptor blockage on cognitive impairments produced by mild traumatic brain injury in mice selectively bred for high (HA) and low (LA) swim-stress induced analgesia that show innate divergence in opioid system activity...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28269777/what-is-the-relationship-of-traumatic-brain-injury-to-dementia
#14
Mario F Mendez
There is a long history linking traumatic brain injury (TBI) with the development of dementia. Despite significant reservations, such as recall bias or concluding causality for TBI, a summary of recent research points to several conclusions on the TBI-dementia relationship. 1) Increasing severity of a single moderate-to-severe TBI increases the risk of subsequent Alzheimer's disease (AD), the most common type of dementia. 2) Repetitive, often subconcussive, mild TBIs increases the risk for chronic traumatic encephalopathy (CTE), a degenerative neuropathology...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28258131/diagnosis-of-endocrine-disease-expanding-the-cause-of-hypopituitarism
#15
REVIEW
Sandra Pekic, Vera Popovic
Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders...
June 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28257413/uncovering-precision-phenotype-biomarker-associations-in-traumatic-brain-injury-using-topological-data-analysis
#16
Jessica L Nielson, Shelly R Cooper, John K Yue, Marco D Sorani, Tomoo Inoue, Esther L Yuh, Pratik Mukherjee, Tanya C Petrossian, Jesse Paquette, Pek Y Lum, Gunnar E Carlsson, Mary J Vassar, Hester F Lingsma, Wayne A Gordon, Alex B Valadka, David O Okonkwo, Geoffrey T Manley, Adam R Ferguson
BACKGROUND: Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. METHODS AND FINDINGS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28242442/genetic-biomarkers-of-posttraumatic-epilepsy-a-systematic-review
#17
REVIEW
Devyn Cotter, Andrew Kelso, Aidan Neligan
INTRODUCTION: Posttraumatic epilepsy (PTE) is caused by traumatic brain injury (TBI) and is an important contributor to the overall social and economic burden of epilepsy. Epidemiological studies suggest that there is a genetic contribution to the development of PTE. Identification of clinically useful genetic biomarkers is important for advancements in diagnosis and treatment of PTE. METHODS: A systematic review was performed on the existing literature of genetic biomarkers of posttraumatic epilepsy (PTE)...
March 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28219400/alleviation-of-secondary-brain-injury-posttraumatic-inflammation-and-brain-edema-formation-by-inhibition-of-factor-xiia
#18
Sarah Hopp, Marc W Nolte, Christian Stetter, Christoph Kleinschnitz, Anna-Leena Sirén, Christiane Albert-Weissenberger
BACKGROUND: Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in the plasma is triggered by activated factor XII. Hence, we set out to study in detail the influence of activated factor XII on the abovementioned pathophysiological features of TBI...
February 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28186446/de-novo-avm-formation-following-venous-sinus-thrombosis-and-prior-avm-resection-in-adults-report-of-2-cases
#19
Siyu Shi, Raghav Gupta, Justin M Moore, Christoph J Griessenauer, Nimer Adeeb, Rouzbeh Motiei-Langroudi, Ajith J Thomas, Christopher S Ogilvy
Brain arteriovenous malformations (AVMs) are traditionally considered congenital lesions, arising from aberrant vascular development during the intrauterine period. Rarely, however, AVMs develop in the postnatal period. Individual case reports of de novo AVM formation in both pediatric and adult patients have challenged the traditional dogma of a congenital origin. Instead, for these cases, a dynamic picture is emerging of AVM growth and development, initially triggered by ischemic and/or traumatic events, coupled with genetic predispositions...
February 10, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28111355/epigenetics-in-epilepsy
#20
REVIEW
K Kobow, I Blümcke
Approximately 50 million people have epilepsy, making it the most common chronic and severe neurological disease worldwide, with increased risk of mortality and psychological and socioeconomic consequences impairing quality of life. More than 30% of patients with epilepsy have inadequate control of their seizures with drug therapy. Any structural brain lesion can provoke epilepsy. However, progression of seizure activity as well as the development of drug-resistance remains difficult to predict, irrespective of the underlying epileptogenic condition, i...
January 19, 2017: Neuroscience Letters
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