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Genetics traumatic brain injury

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https://www.readbyqxmd.com/read/28077398/mild-traumatic-brain-injury-is-associated-with-reduced-cortical-thickness-in-those-at-risk-for-alzheimer-s-disease
#1
Jasmeet P Hayes, Mark W Logue, Naomi Sadeh, Jeffrey M Spielberg, Mieke Verfaellie, Scott M Hayes, Andrew Reagan, David H Salat, Erika J Wolf, Regina E McGlinchey, William P Milberg, Annjanette Stone, Steven A Schichman, Mark W Miller
Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses...
January 11, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28060209/catechol-o-methyltransferase-genotypes-and-parenting-influence-on-long-term-executive-functioning-after-moderate-to-severe-early-childhood-traumatic-brain-injury-an-exploratory-study
#2
Brad G Kurowski, Amery Treble-Barna, Huaiyu Zang, Nanhua Zhang, Lisa J Martin, Keith Owen Yeates, H Gerry Taylor, Shari L Wade
OBJECTIVES: To examine catechol-O-methyltransferase (COMT) rs4680 genotypes as moderators of the effects of parenting style on postinjury changes in parent behavior ratings of executive dysfunction following moderate to severe early childhood traumatic brain injury. SETTING: Research was conducted in an outpatient setting. PARTICIPANTS: Participants included children admitted to hospital with moderate to severe traumatic brain injury (n = 55) or orthopedic injuries (n = 70) between ages 3 and 7 years...
January 5, 2017: Journal of Head Trauma Rehabilitation
https://www.readbyqxmd.com/read/28035654/seven-days-post-injury-fate-and-effects-of-genetically-labelled-adipose-derived-mesenchymal-cells-on-a-rat-traumatic-brain-injury-experimental-model
#3
Ioanna Dori, Spyros Petrakis, Aggeliki Giannakopoulou, Chryssa Bekiari, Ioannis Grivas, Evangelia K Siska, Georgios Koliakos, Georgios C Papadopoulos
Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissue-derived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus...
December 30, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27993598/role-of-neurotoxicants-and-traumatic-brain-injury-in-%C3%AE-synuclein-protein-misfolding-and-aggregation
#4
Dharmin Rokad, Shivani Ghaisas, Dilshan S Harischandra, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Protein misfolding and aggregation are key pathological features of many neurodegenerative diseases including Parkinson's disease (PD) and other forms of human Parkinsonism. PD is a complex and multifaceted disorder whose etiology is not fully understood. However, several lines of evidence support the multiple hit hypothesis that genetic vulnerability and environmental toxicants converge to trigger PD pathology. Alpha-synuclein (α-Syn) aggregation in the brain is an important pathophysiological characteristic of synucleinopathies including PD...
December 16, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27936841/a-career-of-harnessing-group-variability
#5
Donald T Stuss
Neuroscience research, particularly in brain-injured patients, is often hampered by the problems of variability of performance among the individuals included in what seems like a well-defined supposedly homogeneous group. This review presents examples from the author's research in traumatic brain injury (TBI) and the effects of frontal lobe focal pathology to illustrate how variability was explored and "harnessed" to advance the understanding of specific brain-behaviour relations and the role of the frontal lobes in human behaviour...
December 2016: Canadian Journal of Experimental Psychology, Revue Canadienne de Psychologie Expérimentale
https://www.readbyqxmd.com/read/27836728/altered-gene-expression-profile-in-a-mouse-model-of-scn8a-encephalopathy
#6
Ryan S Sprissler, Jacy L Wagnon, Rosie K Bunton-Stasyshyn, Miriam H Meisler, Michael F Hammer
SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27829969/chronic-traumatic-encephalopathy-in-athletes-involved-with-high-impact-sports
#7
Cyrus Safinia, Eric M Bershad, H Brent Clark, Karen SantaCruz, Naila Alakbarova, Jose I Suarez, Afshin A Divani
BACKGROUND AND PURPOSE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease occurring most commonly in athletes and is caused by repeated concussive or subconcussive blows to the head. The main purpose of this review is to evaluate the published literature on chronic traumatic encephalopathy (CTE) in athletes participating in high-impact sports. In particular, we highlight the significance of concussive and subconcussive impacts in multiple sports, elucidate the differences between clinical/pathological features of CTE and related neurodegenerative diseases, and provide an explanation for the variation in clinical presentation between athletes of different sports...
October 2016: Journal of Vascular and Interventional Neurology
https://www.readbyqxmd.com/read/27829172/disordered-app-metabolism-and-neurovasculature-in-trauma-and-aging-combined-risks-for-chronic-neurodegenerative-disorders
#8
REVIEW
Milos D Ikonomovic, Zhiping Mi, Eric E Abrahamson
Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE)...
November 6, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27826691/drd2-c957t-polymorphism-is-associated-with-improved-6-month-verbal-learning-following-traumatic-brain-injury
#9
John K Yue, Ethan A Winkler, Jonathan W Rick, John F Burke, Thomas W McAllister, Sam S Oh, Esteban G Burchard, Donglei Hu, Jonathan Rosand, Nancy R Temkin, Frederick K Korley, Marco D Sorani, Adam R Ferguson, Hester F Lingsma, Sourabh Sharma, Caitlin K Robinson, Esther L Yuh, Phiroz E Tarapore, Kevin K W Wang, Ava M Puccio, Pratik Mukherjee, Ramon Diaz-Arrastia, Wayne A Gordon, Alex B Valadka, David O Okonkwo, Geoffrey T Manley
Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT)...
November 8, 2016: Neurogenetics
https://www.readbyqxmd.com/read/27797810/prevention-of-vincristine-induced-peripheral-neuropathy-by-genetic-deletion-of-sarm1-in-mice
#10
Stefanie Geisler, Ryan A Doan, Amy Strickland, Xin Huang, Jeffrey Milbrandt, Aaron DiAntonio
Peripheral polyneuropathy is a common and dose-limiting side effect of many important chemotherapeutic agents. Most such neuropathies are characterized by early axonal degeneration, yet therapies that inhibit this axonal destruction process do not currently exist. Recently, we and others discovered that genetic deletion of SARM1 (sterile alpha and TIR motif containing protein 1) dramatically protects axons from degeneration after axotomy in mice. This finding fuels hope that inhibition of SARM1 or its downstream components can be used therapeutically in patients threatened by axonal loss...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27769642/comt-val-158-met-polymorphism-is-associated-with-post-traumatic-stress-disorder-and-functional-outcome-following-mild-traumatic-brain-injury
#11
Ethan A Winkler, John K Yue, Adam R Ferguson, Nancy R Temkin, Murray B Stein, Jason Barber, Esther L Yuh, Sourabh Sharma, Gabriela G Satris, Thomas W McAllister, Jonathan Rosand, Marco D Sorani, Hester F Lingsma, Phiroz E Tarapore, Esteban G Burchard, Donglei Hu, Celeste Eng, Kevin K W Wang, Pratik Mukherjee, David O Okonkwo, Ramon Diaz-Arrastia, Geoffrey T Manley
Mild 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 Val(158)Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively...
January 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27762660/time-dependent-effects-of-arginine-vasopressin-v1-receptor-inhibition-on-secondary-brain-damage-after-traumatic-brain-injury
#12
Sandro M Krieg, Raimund Trabold, Nikolaus Plesnila
Arginine-vasopressin (AVP) V1 receptors are known to mediate brain edema formation after traumatic brain injury (TBI). So far, however, AVP V1 receptors were only inhibited by genetic deletion or prior to trauma. Therefore, the current study aimed to determine the therapeutic window of AVP V1 receptor antagonization after TBI. Male C57BL/6 mice (n = 7 per group) were subjected to controlled cortical impact (CCI), and 500 ng of a selective peptide V1 receptor antagonist (V1880) were applied by intracerebroventricular injection 5 min, and 1, 3, and 6 h thereafter...
December 6, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27754853/age-and-diet-affect-genetically-separable-secondary-injuries-that-cause-acute-mortality-following-traumatic-brain-injury-in-drosophila
#13
Rebeccah J Katzenberger, Barry Ganetzky, David A Wassarman
Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries...
December 7, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27687816/upholding-wag-rij-rats-as-a-model-of-absence-epileptogenesis-hidden-mechanisms-and-a-new-theory-on-seizure-development
#14
REVIEW
Emilio Russo, Rita Citraro, Andrew Constanti, Antonio Leo, Annika Lüttjohann, Gilles van Luijtelaar, Giovambattista De Sarro
The WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset...
December 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27677908/abcc8-single-nucleotide-polymorphisms-are-associated-with-cerebral-edema-in-severe-tbi
#15
Ruchira M Jha, Ava M Puccio, David O Okonkwo, Benjamin E Zusman, Seo-Young Park, Jessica Wallisch, Philip E Empey, Lori A Shutter, Robert S B Clark, Patrick M Kochanek, Yvette P Conley
OBJECTIVE: Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE...
September 27, 2016: Neurocritical Care
https://www.readbyqxmd.com/read/27659125/the-potential-for-animal-models-to-provide-insight-into-mild-traumatic-brain-injury-translational-challenges-and-strategies
#16
Sandy R Shultz, Stuart J McDonald, Cole Vonder Haar, Alicia Meconi, Robert Vink, Paul van Donkelaar, Chand Taneja, Grant L Iverson, Brian R Christie
Mild traumatic brain injury (mTBI) is a common health problem. There is tremendous variability and heterogeneity in human mTBI, including mechanisms of injury, biomechanical forces, injury severity, spatial and temporal pathophysiology, genetic factors, pre-injury vulnerability and resilience factors, and clinical outcomes. Animal models greatly reduce this variability and heterogeneity, and provide a means to study mTBI in a rigorous, controlled, and efficient manner. Rodent models, in particular, are time- and cost-efficient, and they allow researchers to measure morphological, cellular, molecular, and behavioral variables in a single study...
September 19, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27650063/a-novel-model-of-traumatic-brain-injury-in-adult-zebrafish-demonstrates-response-to-injury-and-treatment-comparable-with-mammalian-models
#17
Victoria McCutcheon, Eugene Park, Elaine Liu, Pooya Sobhebidari, Jahan Tavakkoli, Xiao-Yan Wen, Andrew J Baker
Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated health care costs. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification...
December 20, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27637394/concussion-mild-traumatic-brain-injury-recoverable-injury-with-potential-for-serious%C3%A2-sequelae
#18
REVIEW
Joshua Kamins, Christopher C Giza
Concussion is increasingly recognized as a major public health issue. Most patients will return to baseline and experience full recovery, although a subset experiences persistent symptoms. Newer animal models and imaging studies are beginning to demonstrate that metabolic and neurovascular resolution may actually take longer than symptomatic recovery. Repeat traumatic brain injury within the metabolic window of dysfunction may result in worsened symptoms and prolonged recovery. The true risk for second impact syndrome appears to be small, and development of cerebral edema after a mild impact may be related to genetic risks rather than serial impacts...
October 2016: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/27637392/pathophysiology-of-traumatic-brain-injury
#19
REVIEW
Melissa J McGinn, John T Povlishock
This article provides a concise overview, at the structural and functional level, of those changes evoked by traumatic brain injury across the spectrum of the disease. Using data derived from animals and humans, the pathogenesis of focal versus diffuse brain damage is presented for consideration of its overall implications for morbidity. Emphasis is placed on contusion and its potential expansion in concert with diffuse changes primarily assessed at the axonal level. Concomitant involvement of neuroexcitation and its role in global and focal metabolic changes is considered...
October 2016: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/27626366/resuscitation-with-pooled-and-pathogen-reduced-plasma-attenuates-the-increase-in-brain-water-content-following-traumatic-brain-injury-and-hemorrhagic-shock-in-rats
#20
Gustav Folmer Genét, Peter Bentzer, Sisse Rye Ostrowski, Pär Ingemar Johansson
Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG(®) [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage...
October 13, 2016: Journal of Neurotrauma
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