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Chung-Ching Chio, Mao-Tsun Lin, Ching-Ping Chang, Hung-Jung Lin
BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD(™) (MLC601) and Astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF-β1. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (120 in number) were used to investigate the contribution of TGF-β1-containing microglia in the MLC601-mediated or the AST-mediated neuroprotection in the brain trauma condition using lateral fluid-percussion injury...
October 19, 2016: European Journal of Clinical Investigation
Vigneswaran Veeramuthu, Vairavan Narayanan, Norlisah Ramli, Aditya Hernowo, Vicknes Waran, Mark W Bondi, Lisa Delano-Wood, Dharmendra Ganesan
OBJECTIVE: To evaluate the extent of persistent neuropsychological impairment in patients with complicated versus uncomplicated mild traumatic brain injury (mTBI). METHODS: 61 patients with mTBI (GCS 13 to 15) were prospectively recruited, categorized according to baseline CT findings, and underwent neuropsychological assessment at initial admission (n=61) as well as at 6 month follow-up (n=30). A paired t-test, Cohen's d effect size calculation, and repeated measure ANOVA were used to establish the differences between the groups in terms of their neuropsychological performance...
October 14, 2016: World Neurosurgery
Alexandra L Clark, Lisa Delano-Wood, Scott F Sorg, Madeleine L Werhane, Karen L Hanson, Dawn M Schiehser
No known studies have directly examined white matter microstructural correlates of cognitive fatigue post-TBI in a Veteran sample. We therefore investigated the relationship between cognitive fatigue and white matter integrity in Veterans with history of mild to moderate TBI (mmTBI). 59 Veterans (TBI = 34, Veteran Controls [VCs] = 25]) with and without history of mmTBI underwent structural 3T DTI scans and completed questionnaires related to cognitive fatigue and psychiatric symptoms. Tractography was employed on six regions of interest, including the anterior and posterior limbs of the internal capsule; genu; body and splenium of the corpus callosum; and cingulum bundle...
October 6, 2016: Brain Imaging and Behavior
Ying Wang, Wen-Yuan Li, Zhi-Gang Li, Li-Xin Guan, Ling-Xiao Deng
Injury to the nervous system induces localized damage in neural structures and neuronal death through the primary insult, as well as delayed atrophy and impaired plasticity of the delicate dendritic fields necessary for interneuronal communication. Excitotoxicity and other secondary biochemical events contribute to morphological changes in neurons following injury. Evidence suggests that various transcription factors are involved in the dendritic response to injury and potential therapies. Transcription factors play critical roles in the intracellular regulation of neuronal morphological plasticity and dendritic growth and patterning...
October 11, 2016: Neuroscience Bulletin
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), YM872, memantine and/or oxATP to block voltage gated Ca(2+) channels, Ca(2+) permeable AMPA receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of primary mixed cortical cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
October 7, 2016: Neuroscience
Isabel López-García, Domokos Gerő, Bartosz Szczesny, Petra Szoleczky, Gabor Olah, Katalin Módis, Kangling Zhang, Gao Jungling, Ping Wu, Lawrence C Sowers, Doug DeWitt, Donald S Prough, Csaba Szabo
BACKGROUND AND PURPOSE: We hypothesized that an in vitro, stretch-based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma. EXPERIMENTAL APPROACH: We screened three neural cell lines (B35, RN33B, SH-SY5Y) subjected to two differentiation methods and selected all-trans-retinoic acid-differentiated B35 rat neuroblastoma cells subjected to rapid stretch injury, coupled with a subthreshold concentration of H2 O2 , for the screen...
October 9, 2016: British Journal of Pharmacology
Marquitta Smith, Thuvan Piehler, Richard Benjamin, Karen L Farizatto, Morgan C Pait, Michael F Almeida, Vladimir V Ghukasyan, Ben A Bahr
Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures. The long-term slice cultures were briefly sealed air-tight in serum-free medium, lowered into a 37°C water-filled tank, and small 1...
October 5, 2016: Experimental Neurology
Ryan C Turner, Brandon P Lucke-Wold, Matthew J Robson, John M Lee, Julian E Bailes
BACKGROUND: Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients. CLINICAL PRESENTATION: This study presents a series of previously unpublished cases, with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE...
August 11, 2016: Brain Injury: [BI]
Pandian Nagakannan, Mohamed Ariff Iqbal, Albert Yeung, James A Thliveris, Mojgan Rastegar, Saeid Ghavami, Eftekhar Eftekharpour
Oxidative damage and aggregation of cellular proteins is a hallmark of neuronal cell death after neurotrauma and chronic neurodegenerative conditions. Autophagy and ubiquitin protease system are involved in degradation of protein aggregates, and interruption of their function is linked to apoptotic cell death in these diseases. Oxidative modification of cysteine groups in key molecular proteins has been linked to modification of cellular systems and cell death in these conditions. Glutathione and thioredoxin systems provide reducing protons that can effectively reverse protein modifications and promote cell survival...
September 28, 2016: Free Radical Biology & Medicine
Nefize Turan, Brandon A Miller, Robert A Heider, Maheen Nadeem, Iqbal Sayeed, Donald G Stein, Gustavo Pradilla
The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments...
September 27, 2016: Journal of Cerebral Blood Flow and Metabolism
Paul M Vespa, Daniel Hirt, Geoffrey T Manley
No abstract text is available yet for this article.
October 2016: Neurosurgery Clinics of North America
Hadie Adams, Angelos G Kolias, Peter J Hutchinson
The general consensus to optimize the care for severe TBI patients is management at specialized neurotrauma centers with neurosurgical and neurocritical care support and the use of guidelines-based standardized protocols. Over the last decade, significant efforts have been made to define neurotrauma treatment guidelines. However, it is important to recognize the heterogeneity of TBI and that the "one-size-fits-all approach" may not always be appropriate for these patients. Knowledge synthesis activities in neurotrauma are important to define future research agendas...
October 2016: Neurosurgery Clinics of North America
Viviane Zelenay, Michael E Arzt, Stefan Bibow, Martin E Schwab, Roland Riek
Functional recovery from central neurotrauma, such as spinal cord injury, is limited by myelin-associated inhibitory proteins. The most prominent example, Nogo-A, imposes an inhibitory cue for nerve fibre growth via two independent domains: Nogo-A-Δ20 (residues 544-725 of the rat Nogo-A sequence) and Nogo-66 (residues 1026-1091). Inhibitory signalling from these domains causes a collapse of the neuronal growth cone via individual receptor complexes, centred around sphingosine 1-phosphate receptor 2 (S1PR2) for Nogo-A-Δ20 and Nogo receptor 1 (NgR1) for Nogo-66...
2016: PloS One
Jignesh D Pandya, Patrick G Sullivan, Lai Yee Leung, Frank C Tortella, Deborah A Shear, Ying Deng-Bryant
Mitochondrial dysfunction is one of the key posttraumatic neuropathological events observed in various experimental models of traumatic brain injury (TBI). The extent of mitochondrial dysfunction has been associated with the severity and time course of secondary injury following brain trauma. Critically, several mitochondrial targeting preclinical drugs used in experimental TBI models have shown improved mitochondrial bioenergetics, together with cortical tissue sparing and cognitive behavioral outcome. Mitochondria, being a central regulator of cellular metabolic pathways and energy producer of cells, are of a great interest for researchers aiming to adopt cutting-edge methodology for mitochondrial bioenergetics assessment...
2016: Methods in Molecular Biology
Ying Deng-Bryant, Lai Yee Leung, Krista Caudle, Frank Tortella, Deborah Shear
The Morris water maze (MWM) task is one of the most widely used and versatile tools in behavioral neuroscience for evaluating spatial learning and memory. With regard to detecting cognitive deficits following central nervous system (CNS) injuries, MWM has been commonly utilized in various animal models of neurotrauma, such as fluid percussion injury (FPI), cortical controlled impact (CCI) injury, weight-drop impact injury, and penetrating ballistic-like brain injury (PBBI). More importantly, it serves as a therapeutic index for assessing the efficacy of treatment interventions on cognitive performance following neurotrauma...
2016: Methods in Molecular Biology
Floyd J Thompson, Jiamei Hou, Prodip K Bose
Successful therapy for TBI disabilities awaits refinement in the understanding of TBI neurobiology, quantitative measurement of treatment-induced incremental changes in recovery trajectories, and effective translation to human TBI using quantitative methods and protocols that were effective to monitor recovery in preclinical models. Details of the specific neurobiology that underlies these injuries and effective quantitation of treatment-induced changes are beginning to emerge utilizing a variety of preclinical and clinical models (for reviews see (Morales et al...
2016: Methods in Molecular Biology
Dennis W Simon, Vincent M Vagni, Patrick M Kochanek, Robert S B Clark
Patients with severe traumatic brain injury (TBI) frequently present with concomitant injuries that may cause secondary brain injury and impact outcomes. Animal models have been developed that combine contemporary models of TBI with a secondary neurologic insult such as hypoxia, shock, long bone fracture, and radiation exposure. Combined injury models may be particularly useful when modeling treatment strategies and in efforts to map basic research to a heterogeneous patient population. Here, we review these models and their collective contribution to the literature on TBI...
2016: Methods in Molecular Biology
Johan Davidsson, Mårten Risling
Physical trauma in the central nervous system (CNS) is usually the result of a number of forces in different directions and dimensions. A large number of experimental models have been developed to improve the possibilities to understand the outcome of CNS trauma. In this chapter, we will describe the need for a variety of experimental models for research on traumatic brain injury (TBI) and spinal cord injury (SCI). Models can serve different needs, such as: to test new treatments for injuries, to reveal thresholds for injuries, to provide a better understanding of injury mechanisms, or to test tools and methods for translation between experiments and clinical data...
2016: Methods in Molecular Biology
Zaynab Jaber, Patrick Aouad, Mohamad Al Medawar, Hisham Bahmad, Hussein Abou-Abbass, Hiba Ghandour, Stefania Mondello, Firas Kobeissy
Years of research in the field of neurotrauma have led to the concept of applying systems biology as a tool for biomarker discovery in traumatic brain injury (TBI). Biomarkers may lead to understanding mechanisms of injury and recovery in TBI and can be potential targets for wound healing, recovery, and increased survival with enhanced quality of life. The literature available on neurotrauma studies from both animal and clinical studies has provided rich insight on the molecular pathways and complex networks of TBI, elucidating the proteomics of this disease for the discovery of biomarkers...
2016: Methods in Molecular Biology
Zaynab Jaber, Patrick Aouad, Mohamad Al Medawar, Hisham Bahmad, Hussein Abou-Abbass, Firas Kobeissy
The application of systems biology tools in analyzing heterogeneous data from multiple sources has become a necessity, especially in biomarker discovery. Such tools were developed with several approaches to address different types of research questions and hypotheses. In the field of neurotrauma and traumatic brain injury (TBI), three distinct approaches have been used so far as systems biology tools, namely functional group categorization, pathway analysis, and protein-protein interaction (PPI) networks. The databases allow for query of the system to identify candidate targets which can be further studied to elucidate potential downstream biomarkers indicative of disease progression, severity, and improvement...
2016: Methods in Molecular Biology
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