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Journal of Neurotrauma

Ibrahim Jalloh, Adel Helmy, Duncan Howe, Richard J Shannon, Peter Grice, Andrew Mason, Clare N Gallagher, Michael Murphy, John Pickard, David Menon, Thomas Adrian Carpenter, Peter John Hutchinson, Keri Carpenter
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in 9 severe TBI patients' brains, 5 non-TBI brain surgical patients, and 5 resting muscle (non-TBI) patients were perfused (24h in brain, 8h in muscle) with 8 mmol/L sodium 3‑13C lactate...
April 25, 2018: Journal of Neurotrauma
Johanna Flygt, Karsten Ruscher, Amanda Norberg, Anis Mir, Hermann Gram, Fredrik Clausen, Niklas Marklund
Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI although may plausibly be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI behavioral outcome was improved. To evaluate the role of IL-1β on OL cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at 2, 7 and 14 days post-injury...
April 25, 2018: Journal of Neurotrauma
Aaron M Williams, Isabel S Dennahy, Umar F Bhatti, Ihab Halaweish, Ye Xiong, Panpan Chang, Vahagn C Nikolian, Kiril Chtraklin, Jordana Brown, Yanlu Zhang, Zheng Gang Zhang, Michael Chopp, Benjamin Buller, Hasan B Alam
Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remains a leading cause of preventable death worldwide. Mesenchymal stem cell-derived exosomes have demonstrated promise in small animal models of neurologic injury. To investigate the effects of exosome treatment in a clinically realistic large animal model, Yorkshire swine were subjected to TBI and HS. Animals were maintained in shock for 2 hours prior to resuscitation with normal saline (NS). Animals were then either resuscitated with NS (3 x volume of shed blood) or with the same volume of NS with delayed exosome administration (1x10<sup>13</sup> particles/4ml) (n=5/cohort)...
April 25, 2018: Journal of Neurotrauma
Frederick Kofi Korley, John K Yue, David Wilson, Kevin Hrusovsky, Ramon Diaz-Arrasta, Adam R Ferguson, Esther Lim Yuh, Pratik Mukherjee, Kevin K W Wang, Alex Valadka, Ava Puccio, David O Okonkwo, Geoffrey Manley
Traumatic brain injury (TBI) results in heterogeneous pathology affecting multiple cells and tissue types in the brain. It is likely that assessment of such complexity will require simultaneous measurement of multiple molecular biomarkers in a single sample of biological fluid. We measured glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NF-L) and total tau in plasma samples obtained from 107 subjects enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) Study using the Quanterix Simoa 4-Plex assay...
April 25, 2018: Journal of Neurotrauma
Janja Kuharić, Kristina Grabusic, Vlatka Sotosek Tokmadzic, Sanja Štifter, Ksenija Tulić, Olga Shevchuk, Pero Lučin, Alan Šustić
Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in body fluids and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. However, properties of intracranial EVs early after TBI have not been characterized...
April 25, 2018: Journal of Neurotrauma
Maryse C Cnossen, Joukje van der Naalt, Jacoba M Spikman, Daan Nieboer, John K Yue, Ethan A Winkler, Geoffrey Manley, Nicole von Steinbuechel, Suzanne Polinder, Ewout W Steyerberg, Hester Lingsma
Persistent post-concussion symptoms (PPCS) occur frequently after mild traumatic brain injury (mTBI). The identification of patients at risk for poor outcome remains challenging since valid prediction models are missing. The objectives of the current study were to assess the quality and clinical value of prediction models for PPCS , and to develop a new model based on the synthesis of existing models and addition of complaints at emergency department (ED). MTBI patients (Glasgow Coma Scale score 13-15) were prospectively recruited from three Dutch level I trauma centers between 2013-2015 in the UPFRONT study...
April 25, 2018: Journal of Neurotrauma
Emily A Evans, David Asuzu, Nathan Cook, Paul Caruso, Elise Townsend, Beth Costine-Bartell, Carla Fortes-Monteiro, Gillian Hotz, Ann-Christine Duhaime
This study examined the relationship between acute neuroimaging, host and injury factors and parent-reported traumatic brain injury-related symptoms in children with non-critical head injury at 2 weeks and 3 months after injury. Data were collected prospectively on 45 subjects aged 3-16 years old enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. Subjects had rapid recovery of mental status (Glasgow Coma Score(GCS)=15 within 24 hours), and had no clinical need for neurosurgical intervention...
April 21, 2018: Journal of Neurotrauma
Emoke Olah, Laszlo Poto, Peter Hegyi, Imre Szabo, Petra Hartmann, Margit Solymar, Erika Petervari, Marta Balasko, Tamas Habon, Zoltan Rumbus, Judit Tenk, Ildiko Rostas, Jordan Weinberg, Andrej A Romanovsky, Andras Garami
Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the mortality of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure inter-study homogeneity...
April 21, 2018: Journal of Neurotrauma
Wei Zhao, Songbai Ji
Advanced neuroimaging provides new opportunities to enhance head injury models, including the incorporation of white matter (WM) structural anisotropy. However, information from high-resolution neuroimaging has to be "down-sampled" to match typically coarse brain mesh. To understand how this mesh-image resolution mismatch affects impact simulation and subsequent response sampling, we compared three competing anisotropy implementations (using either voxels, tractography, or a multiscale submodeling), two response sampling strategies (element-wise or tractography-based), and two region segmentation methods (brain mesh vs...
April 21, 2018: Journal of Neurotrauma
Nandadevi Patil, Vincent Truong, Mackenzie H Holmberg, Nicolas S Lavoie, Mark R McCoy, James R Dutton, Eric G Holmberg, Ann M Parr
There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. We have removed existing scar tissue in chronically contused rat spinal cord using a rose Bengal-based photo ablation approach...
April 19, 2018: Journal of Neurotrauma
Max Wintermark, Ying Li, Victoria Y Ding, Yingding Xu, Bin Jiang, Robyn L Ball, Michael Zeineh, Alisa Gean, Pina Sanelli
To develop an outcome-based NeuroImaging Radiological Interpretation System (NIRIS) for acute traumatic brain injury (TBI) patients that would standardize the interpretation of non-contrast head CTs and consolidate imaging findings into ordinal severity categories that would inform specific patient management actions and that could be used as a clinical decision support tool. We retrospectively identified all patients transported to our emergency department by ambulance or helicopter, for whom a trauma alert was triggered per established criteria and who underwent a non-contrast head CT due to suspicion of TBI, between November 2015 and April 2016...
April 18, 2018: Journal of Neurotrauma
Noah D Silverberg, William Panenka, Grant L Iverson
Characterizing psychological factors that contribute to persistent symptoms after mild traumatic brain injury (MTBI) can inform early intervention. To determine whether fear avoidance, a known risk factor for chronic disability after musculoskeletal injury, is associated with worse clinical outcomes from MTBI, adults were recruited from four outpatient MTBI clinics and assessed at their first clinic visit (M=2.7, SD=1.5 weeks post-injury) and again 4-5 months later. Of 273 patients screened, 102 completed the initial assessment and 87 returned for the outcome assessment...
April 18, 2018: Journal of Neurotrauma
Jefferson R Wilson, Blessing Jaja, Brian K Kwon, James Guest, James Shields Harrop, Bizhan Aarabi, Christopher Shaffrey, Jetan Badhiwala, Elizabeth Toups, Robert Grossman, Michael G Fehlings
The course, treatment response and recovery potential following acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. However, there are limited data focused on thoracic-level injuries. A cohort of 86 patients from the prospectively maintained North American Clinical Trials Network (NACTN) SCI registry were identified and studied to characterize the patterns of neurological recovery as well as to determine rates of acute hospital mortality and pulmonary complications...
April 18, 2018: Journal of Neurotrauma
Hefan He, Yingying Zhou, Yilin Zhou, Jiayuan Zhuang, Xu He, Siyuan Wang, Wenping Lin
Excessive neuroinflammation aggravates neurological damage after spinal cord injury (SCI). Controlling neuroinflammation might favor neuroregeneration and tissue repair. Dexmedetomidine is reported to inhibit post-SCI neuroinflammation in previous research. In the current study, to determine the mechanisms by which dexmedetomidine inhibits neuroinflammation, we tested the effect of dexmedetomidine hydrochloride on microglia in vitro and in a rat SCI model. We found that dexmedetomidine hydrochloride up-regulated programmed cell death protein 1 (PD-1), an immunoregulatory molecule, in activated microglia but not in resting microglia...
April 18, 2018: Journal of Neurotrauma
Giovanna Casili, Michela Campolo, Irene Paterniti, Marika Lanza, Alessia Filippone, Salvatore Cuzzocrea, Emanuela Esposito
Traumatic brain injury (TBI) is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory, and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in pre-clinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI)...
April 17, 2018: Journal of Neurotrauma
Talin Babikian, Jeffry R Alger, Monica U Ellis-Blied, Christopher C Giza, Emily Dennis, Alexander Olsen, Richard Mink, Christopher Babbitt, Jeffrey Johnson, Paul Thompson, Robert F Asarnow
Diffuse axonal injury contributes to the long-term functional morbidity observed following pediatric moderate/severe traumatic brain injury (msTBI). Whole-Brain Proton Magnetic Resonance Echo-Planar Spectroscopic Imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and CC function assessed by interhemispheric transfer time (IHTT) using an Event Related Potential paradigm) was also explored...
April 13, 2018: Journal of Neurotrauma
Weihua Wang, Alexander Kevin Zinsmaier, Ethan Firestone, Ruizhu Lin, Tatiana A Yatskievych, Sungchil Yang, Jinsheng Zhang, Shaowen Bao
Traumatic brain injury (TBI) is a major cause of neurological disorder and death in civilian and military populations (citation?). It comprises two components-direct injury from the traumatic impact and secondary injury from ensuing neural inflammatory responses. Blocking tumor necrosis factor-alpha (TNF-α), a central regulator of neural inflammation, has been shown to improve functional recovery after TBI. However, the mechanisms underlying those therapeutic effects are still poorly understood. Here we examined effects of 3,6'-dithiothalidomide (dTT), a potentially therapeutic TNF-α inhibitor, in mice with blast-induced TBI...
April 13, 2018: Journal of Neurotrauma
Parag Gad, Sujin Lee, Nicholas Terrafranca, Hui Zhong, Amanda Turner, Yury Gerasimenko, Victor Reggie Edgerton
Paralysis of the upper extremities following cervical spinal cord injury (SCI) significantly impairs one's ability to live independently. While regaining hand function or grasping ability is considered one of the most desired functions in tetraplegics, limited therapeutic development in this direction has been demonstrated to date in humans with a high, severe cervical injury. The underlying hypothesis is after severe cervical SCI, nonfunctional sensory-motor networks within the cervical spinal cord can be transcutaneously neuromodulated to physiological states which enables and amplifies voluntary control of the hand...
April 13, 2018: Journal of Neurotrauma
Liang Wen, Wen-Dong You, Hao Wang, Yuanyuan Meng, Jun-Feng Feng, Xiaofeng Yang
Increasing evidence indicated that activated microglia play an important role in the inflammatory response following traumatic brain injury (TBI). Inhibiting M1 and stimulating M2 activated microglia have demonstrated protective effects in several animal models of central nervous system diseases. However, it is not clear whether the polarization of microglia to M2 attenuates axonal injury following TBI. In this study, we used a lateral fluid percussion injury device to induce axonal injury in mice. Mice were randomly assigned to the sham, TBI, TBI + rosiglitazone (PPAR-γ agonist), and TBI + GW9662 (PPAR-γ antagonist) groups...
April 13, 2018: Journal of Neurotrauma
Mitchell T Caprelli, Andrea J Mothe, Charles Tator
Current biomarker research in spinal cord injury (SCI) and traumatic brain injury has focused on a number of structural protein candidates, including the microtubule-associated protein tau. Evidence from models of traumatic brain injury has demonstrated that hyperphosphorylation of tau (p-tau) occurs within injured axons and provides evidence of its utility as a biomarker in brain injury; however, the potential of p-tau as a biomarker for SCI is not yet known. Therefore, the present study determined whether tau is hyperphosphorylated within injured spinal cord axons, and then examined cerebrospinal fluid (CSF) and serum concentrations of p-tau and total-tau protein, following a clinically relevant severe impact-compression SCI in rats...
April 12, 2018: Journal of Neurotrauma
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