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https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#1
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28420864/insulin-growth-factor-1-protects-neural-stem-cells-against-apoptosis-induced-by-hypoxia-through-akt-mitogen-activated-protein-kinase-extracellular-signal-regulated-kinase-akt-mapk-erk-pathway-in-hypoxia-ishchemic-encephalopathy
#2
Bing Zhao, Zebao Zheng
BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth and acts as potential therapy for traumatic brain injury. This study was designed to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs separated from the hippocampus of rat. NSCs were divided into four groups: cells under normoxic conditions that acted as controls (C group), cells under hypoxia (H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the IGF-1 receptor (HIP group)...
April 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28420443/tau-phosphorylation-induced-by-severe-closed-head-traumatic-brain-injury-is-linked-to-the-cellular-prion-protein
#3
Richard Rubenstein, Binggong Chang, Natalia Grinkina, Eleanor Drummond, Peter Davies, Meir Ruditzky, Deep Sharma, Kevin Wang, Thomas Wisniewski
Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrP(C)) and amyloid-β oligomers (Aβo). This PrP(C)-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD transgenic mice lacking PrP(C) accumulate Aβ, but show normal survival and no loss of spatial learning and memory suggesting that PrP(C) functions downstream of Aβo production but upstream of intracellular toxicity within neurons...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28413156/exposure-of-the-amino-terminus-of-tau-is-a-pathological-event-in-multiple-tauopathies
#4
Benjamin Combs, Nicholas M Kanaan
Pathological changes to the tau protein, including conformational changes and aggregation, are major hallmarks of a group of neurodegenerative disorders known as tauopathies. Among the conformational changes are alterations involving the extreme amino terminus of the protein, known as the phosphatase-activating domain (PAD). Aberrant PAD exposure induces a signaling cascade that leads to disruption of axonal transport, a critical function for neuronal survival. Conformational display of PAD is an early marker of pathological tau in Alzheimer disease (AD), but its role in other tauopathies has yet to be firmly established...
April 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28413125/transient-dysautonomia-in-an-acute-phase-of-encephalopathy-with-biphasic-seizures-and-late-reduced-diffusion
#5
Yuko Ichimiya, Noriyuki Kaku, Yasunari Sakai, Fumiya Yamashita, Wakato Matsuoka, Mamoru Muraoka, Satoshi Akamine, Soichi Mizuguchi, Michiko Torio, Yoshitomo Motomura, Yuichiro Hirata, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki Torisu, Hidetoshi Takada, Yoshihiko Maehara, Shouichi Ohga
Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection...
April 13, 2017: Brain & Development
https://www.readbyqxmd.com/read/28403205/spontaneous-diseases-in-captive-ratites-struthioniformes-in-northwestern-germany-a-retrospective-study
#6
Aimara Bello, Samuel Frei, Martin Peters, Anne Balkema-Buschmann, Wolfgang Baumgärtner, Peter Wohlsein
A retrospective study was carried out to define the spectrum of spontaneous diseases in ostriches and few other captive ratites, order Struthioniformes, in northwestern Germany. The investigation included 71 ratites necropsied between 1968 and 2014. They consisted of 54 ostriches, 5 emus, and 12 rheas with 37 adults, 23 juveniles and 11 neonates and embryonated eggs. Necropsy reports were reviewed, histologic preparations were re-examined and additional histochemical and immunohistochemical stains were carried out in selected cases...
2017: PloS One
https://www.readbyqxmd.com/read/28392702/hepatic-encephalopathy-what-the-multidisciplinary-team-can-do
#7
REVIEW
Andy Liu, Eric R Yoo, Osama Siddique, Ryan B Perumpail, George Cholankeril, Aijaz Ahmed
Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity...
2017: Journal of Multidisciplinary Healthcare
https://www.readbyqxmd.com/read/28390515/chronic-traumatic-encephalopathy-known-causes-unknown-effects
#8
REVIEW
Diego Iacono, Sharon B Shively, Brian L Edlow, Daniel P Perl
Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated...
May 2017: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/28370398/tau-aggregates-where-when-why-and-what-consequences
#9
EDITORIAL
Matthew P Frosch
Neuropathologists have been aware of neurofibrillary tangles for more than a century following their description as part of Alois Alzheimer's initial report. Since those early days, our understanding of the relationship of this particular type of cellular inclusion associated with neurodegeneration has continually broadened. Textbooks, now a partially antiquated concept, commonly list a range of disorders as being associated with tangles -NDASH- including typical neurodegenerative diseases (Alzheimer disease [AD], forms of frontotemporal lobar degenerations [FTLD-tau], progressive supranuclear palsy [PSP], corticobasal degeneration [CBD], primary aged related tauopathy [PART]), secondary degenerative diseases such as chronic traumatic encephalopathy, metabolic disease (Niemann-Pick disease type C) and infections (SSPE)...
April 2, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28370167/tau-aggregates-where-when-why-and-what-consequences
#10
EDITORIAL
Matthew P Frosch
Neuropathologists have been aware of neurofibrillary tangles for more than a century following their description as part of Alois Alzheimer's initial report. Since those early days, our understanding of the relationship of this particular type of cellular inclusion associated with neurodegeneration has continually broadened. Textbooks, now a partially antiquated concept, commonly list a range of disorders as being associated with tangles -NDASH- including typical neurodegenerative diseases (Alzheimer disease [AD], forms of frontotemporal lobar degenerations [FTLD-tau], progressive supranuclear palsy [PSP], corticobasal degeneration [CBD], primary aged related tauopathy [PART]), secondary degenerative diseases such as chronic traumatic encephalopathy, metabolic disease (Niemann-Pick disease type C) and infections (SSPE)...
March 30, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28369828/raised-intracranial-pressure-and-retinal-haemorrhages-in-childhood-encephalopathies
#11
Robert A Minns, Patricia A Jones, Anamika Tandon, Brian W Fleck, Alan O Mulvihill, Fiona C Minns
AIM: To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies. METHOD: A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging...
March 29, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28365421/quantitative-validation-of-a-nonlinear-histology-mri-coregistration-method-using-generalized-q-sampling-imaging-in-complex-human-cortical-white-matter
#12
Mihika Gangolli, Laurena Holleran, Joong Hee Kim, Thor D Stein, Victor Alvarez, Ann C McKee, David L Brody
Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images...
March 30, 2017: NeuroImage
https://www.readbyqxmd.com/read/28347679/chronic-traumatic-encephalopathy-the-cellular-sequela-to-repetitive-brain-injury
#13
REVIEW
Alexander R Vile, Leigh Atkinson
This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities...
March 24, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28338593/clinical-correlates-to-assist-with-cte-diagnosis-insights-from-a-novel-rodent-repeat-concussion-model
#14
Gretchen M Thomsen, Ara Ko, Megan Y Harada, Annie Ma, Livia Wyss, Patricia Haro, Jean-Philippe Vit, Pablo Avalos, Navpreet Dhillon, Noell Cho, Oksana Shelest, Eric J Ley
INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. CTE symptoms include changes in mood, behavior, cognition and motor function, however CTE is only currently diagnosed post-mortem. Using a rat model of recurrent traumatic brain injury (TBI) we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed skull, mild TBI was administered once per week to 35 WT rats, 8 rats received 2 injuries ('2xTBI'), 27 rats received 5 injuries ('5xTBI') and 13 rats were sham controls...
March 23, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28335005/tdp-43-suppresses-tau-expression-via-promoting-its-mrna-instability
#15
Jianlan Gu, Feng Wu, Wen Xu, Jianhua Shi, Wen Hu, Nana Jin, Wei Qian, Xinglong Wang, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
In the brains of individuals with Alzheimer's disease (AD) and chronic traumatic encephalopathy, tau pathology is accompanied usually by intracellular aggregation of transactive response DNA-binding protein 43 (TDP-43). However, the role of TDP-43 in tau pathogenesis is not understood. Here, we investigated the role of TDP-43 in tau expression in vitro and in vivo. We found that TDP-43 suppressed tau expression by promoting its mRNA instability through the UG repeats of its 3΄-untranslated region (3΄-UTR)...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28327371/longitudinal-changes-in-linguistic-complexity-among-professional-football-players
#16
Visar Berisha, Shuai Wang, Amy LaCross, Julie Liss, Pamela Garcia-Filion
Reductions in spoken language complexity have been associated with the onset of various neurological disorders. The objective of this study is to analyze whether similar trends are found in professional football players who are at risk for chronic traumatic encephalopathy. We compare changes in linguistic complexity (as indexed by the type-to-token ratio and lexical density) measured from the interview transcripts of players in the National Football League (NFL) to those measured from interview transcripts of coaches and/or front-office NFL executives who have never played professional football...
March 16, 2017: Brain and Language
https://www.readbyqxmd.com/read/28326890/functional-and-molecular-correlates-following-single-and-repeated-rat-closed-head-concussion-indices-of-vulnerability-following-brain-injury
#17
Andrea Mountney, Angela Boutte, Casandra M Cartagena, William J Flerlage, David Johnson, Chanyang Rho, Xi-Chun M Lu, Angela M Yarnell, Sean R Marcsisin, Jason Sousa, Chau Vuong, Victor E Zottig, Lai Yee Leung, Ying Deng-Bryant, Janice Gilsdorf, Frank C Tortella, Deborah A Shear
Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). Isolated concussions frequently produce acute neurological impairments; however, individuals typically recover spontaneously within a short time frame. In contrast, brain injuries resulting from multiple concussions can result in cumulative damage and elevated risk of developing chronic brain pathologies, including chronic traumatic encephalopathy (CTE). Increased attention has focused on identification of diagnostic markers that can prognostically serve as indices of brain health after injury, revealing the temporal profile of vulnerability to a second insult...
March 22, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28316319/epileptic-spasms-in-paediatric-post-traumatic-epilepsy-at-a-tertiary-referral-centre
#18
Jun T Park, Harry T Chugani
To recognize epileptic spasms (ES) as a seizure type after traumatic brain injury (TBI), accidental or non-accidental, in infants and children. In the process, we aim to gain some insight into the mechanisms of epileptogenesis in ES. A retrospective electronic chart review was performed at the Children's Hospital of Michigan from 2002 to 2012. Electronic charts of 321 patients were reviewed for evidence of post-traumatic epilepsy. Various clinical variables were collected including age at TBI, mechanism of trauma, severity of brain injury, electroencephalography/neuroimaging data, and seizure semiology...
March 17, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28291783/oesophageal-heat-exchangers-with-a-diameter-of-11mm-or-14-7mm-are-equally-effective-and-safe-for-targeted-temperature-management
#19
Daniel C Schroeder, Maria Guschlbauer, Alexandra C Maul, Daniel A Cremer, Ingrid Becker, David de la Puente Bethencourt, Peter Paal, Stephan A Padosch, Wolfgang A Wetsch, Thorsten Annecke, Bernd W Böttiger, Anja Sterner-Kock, Holger Herff
BACKGROUND: Targeted temperature management (TTM) is widely used in critical care settings for conditions including hepatic encephalopathy, hypoxic ischemic encephalopathy, meningitis, myocardial infarction, paediatric cardiac arrest, spinal cord injury, traumatic brain injury, ischemic stroke and sepsis. Furthermore, TTM is a key treatment for patients after out-of-hospital cardiac-arrest (OHCA). However, the optimal cooling method, which is quick, safe and cost-effective still remains controversial...
2017: PloS One
https://www.readbyqxmd.com/read/28275351/botulinum-toxin-is-effective-in-the-management-of-neurogenic-dysphagia-clinical-electrophysiological-findings-and-tips-on-safety-in-different-neurological-disorders
#20
Enrico Alfonsi, Domenico A Restivo, Giuseppe Cosentino, Roberto De Icco, Giulia Bertino, Antonio Schindler, Massimiliano Todisco, Mauro Fresia, Andrea Cortese, Paolo Prunetti, Matteo C Ramusino, Arrigo Moglia, Giorgio Sandrini, Cristina Tassorelli
Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15-20 U) into the CP muscle under electromyographic guidance...
2017: Frontiers in Pharmacology
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