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Journal of Neurotrauma

Jessica Dennis, Aaron Michael Yengo-Kahn, Paul Kirby, Gary S Solomon, Nancy J Cox, Scott L Zuckerman
Post-concussion syndrome (PCS) is characterized by persistent cognitive, somatic, and emotional symptoms after a mild traumatic brain injury (mTBI). Genetic and other biological variables may contribute to PCS etiology, and the emergence of biobanks linked to electronic health records (EHR) offers new opportunities for research on PCS. We sought to validate the use of EHR data of PCS patients by comparing two diagnostic algorithms deployed in the Vanderbilt University Medical Center de-identified database of 2...
February 16, 2019: Journal of Neurotrauma
Jussi P Posti, Riikka Sk Takala, Linnéa Lagerstedt, Alex Mountfort Dickens, Iftakher Hossain, Mehrbod Mohammadian, Henna Maria Ala-Seppälä, Janek Frantzén, Mark Van Gils, Peter John Hutchinson, Ari J Katila, Henna-Riikka Maanpää, David Menon, Virginia Newcombe, Jussi Tallus, Kevin Hrusovsky, David Wilson, Jessica Gill, Jean-Charles Sanchez, Olli Tenovuo, Henrik Zetterberg, Kaj Blennow
The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating CT-negative and CT-positive patients with TBI, utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24h from admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B) and tau were measured...
February 14, 2019: Journal of Neurotrauma
Wei Liu, Ping-Hong Yeh, Dominic Nathan, Chihwa Song, Helena Wu, Grant H Bonavia, John M Ollinger, Gerard Riedy
Brain venous volume above the lateral ventricle in military patients with TBI was assessed using two segmentation approaches on susceptibility weighted images (SWI) and quantitative susceptibility maps (QSM). This retrospective study included a total of 147 subjects: 14 patients with severe TBI; 38 patients with moderate TBI; 58 patients with mild TBI (28 with blast related injuries and 30 with nonblast related injuries) and 37 control subjects without history of TBI. Using the multiscale vessel enhancement filter on SWI images, patients with severe TBI demonstrated significantly higher segmented venous volumes compared to the controls...
February 14, 2019: Journal of Neurotrauma
Eva-Verena Griemert, Jana Hedrich, Tobias Hirnet, Serge Christian Thal
Plasminogen activator inhibitor type 2 (PAI-2 / SerpinB2) inhibits extracellular urokinase plasminogen activator (uPA). Under physiological conditions PAI-2 is expressed at low levels, but is rapidly induced by inflammatory triggers. It is a negative regulator of fibrinolysis and serves to stabilize clots. In the present study PAI-2 expression is upregulated 25-fold in pericontusional brain tissue at 6h after traumatic brain injury (TBI) with a maximum increase of 87-fold at 12h. To investigate a potentially detrimental influence of PAI-2 on secondary posttraumatic processes, male PAI-2 deficient (PAI-2-KO) and wild-type mice (WT) were subjected to TBI by controlled cortical impact injury (CCI)...
February 13, 2019: Journal of Neurotrauma
Chen-Guang Yu, Vimala Bondada, Sarbani Ghoshal, Ranjana Singh, Christina K Pistilli, Kavi Dayaram, Hina Iqbal, Madison Sands, Kate Davis, Subbarao Bondada, James W Geddes
We previously reported the serendipitous observation that Fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, Flubendazole, using a rat spinal cord contusion injury model...
February 12, 2019: Journal of Neurotrauma
Mihir V Patel, Emily Sewell, Samantha Dickson, Hyuck Kim, David Meaney, Bonnie L Firestein
Postsynaptic density 95 (PSD-95), the major scaffold protein at excitatory synapses, plays a major role in mediating intracellular signaling by synaptic N-methyl-D-aspartate (NMDA) type glutamate receptors. Despite the fact that much is known about the role of PSD-95 in NMDA-mediated toxicity, less is known about its role in mechanical injury, and more specifically, in traumatic brain injury. Given that neural circuitry is disrupted after TBI and that PSD-95 and its interactors end-binding protein 3 (EB3) and adenomatous polyposis coli (APC) shape dendrites, we examined whether changes to these proteins and their interactions occur after brain trauma...
February 12, 2019: Journal of Neurotrauma
Lihong Lu, Haojie Mao
Controlled cortical impact (CCI) is a widely used laboratory neurotrauma model to study traumatic brain injury. During CCI, the brain is damaged by an impactor tip, which travels along its axial direction to a pre-defined depth at a pre-set speed. A recent study, however, using high-speed imaging analysis demonstrated that the impactor tip of an electromagnetically driven CCI device experienced repeated impacts and lateral movements, rather than a single axial impact. How these repeated impacts and lateral movements affect internal brain stresses/strains-which are the direct cause of neuronal damage and affect the accuracy and reproducibility of CCI-remains unknown...
February 7, 2019: Journal of Neurotrauma
Zhou Zhou, Xiaogai Li, Svein Kleiven
Acute subdural hematoma (ASDH) due to bridging vein (BV) rupture is a frequent and lethal head injury, especially in the elderly. Brain atrophy has been hypothesized to be a primary pathogenesis associated with the increased risk of ASDH in the elderly. Though decades of biomechanical endeavours have been made to elucidate the potential mechanisms, a thorough explanation for this hypothesis appears lacking. Thus, a recently improved finite element head model, in which the brain-skull interface was modelled using a fluid-structure interaction (FSI) approach with special treatment of the cerebrospinal fluid as arbitrary Lagrangian-Eulerian fluid formulation, is used to partially address this understanding gap...
February 4, 2019: Journal of Neurotrauma
Kate E Hoy, Susan McQueen, David Elliot, Sally Herring, Jerome J Maller, Paul B Fitzgerald
Depression following a Traumatic Brain Injury (TBI) is common and difficult to treat using standard approaches. The current study investigated, for the first time, Transcranial Magnetic Stimulation for the treatment of post TBI depression. We specifically assessed the safety, tolerability and efficacy of TMS in this patient population. We also explored cognitive outcomes. 21 patients with a current episode of major depression subsequent to a TBI participated in a randomized double blind placebo controlled trial of rTMS...
February 2, 2019: Journal of Neurotrauma
Susan Farr, Michael L Niehoff, Vijaya B Kumar, Deborah Anne Roby, John E Morley
Traumatic brain injury (TBI) has many long-term consequences including impairment in memory and changes in mood. GSK-3β in its phosphorylated form (p-GSK-3β) is considered to be a major contributor to memory problems that occur with TBI. We have developed an antisense which targets the GSK-3β (GAO) gene. Using a model of closed head concussive TBI, we subjected mice to TBI and injected GAO or a random antisense (RAO) 15 minutes post-injury. One week post-injury mice were tested in object recognition with 24 hour delay...
February 1, 2019: Journal of Neurotrauma
Kimberly Mendoza, Paul J Derry, Leela Cherian, Robert Garcia, Lizanne Nilewski, J Clay Goodman, Lamin Mbye, Claudia S Robertson, James M Tour, Thomas Kent
Hypotension worsens outcome after all severities of traumatic brain injury (TBI), with loss of cerebral autoregulation a potential contributor. Previously, we demonstrated that intravenous injection of a high capacity catalytic antioxidant, poly(ethylene)glycol conjugated hydrophilic carbon clusters (PEG-HCCs) rapidly restored cerebral perfusion and acutely restored brain oxidative balance in a TBI model complicated by hemorrhagic hypotension without evidence of toxicity. Here, we tested whether these acute effects translated into behavioral and structural benefit...
February 1, 2019: Journal of Neurotrauma
Andrew Robert Stevens, Isabel Ng, Adel Helmy, Peter John Hutchinson, David Menon, Ari Ercole
Cortical spreading depolarisation (CSD) is an emerging mode of secondary neuronal damage in acute brain injury (ABI). Subsequent repolarisation is a metabolic process requiring glucose. Instances of CSD and glucose derangement are both linked to poor neurological outcome, but their causal inter-relationship is not fully defined. This systematic review seeks to evaluate the available human evidence studying CSD and glucose to further understand their dynamic relationship. We conducted a systematic review of studies examining CSD through electrocorticography and cerebral/systemic glucose concentrations in ABI, excluding animal studies...
January 31, 2019: Journal of Neurotrauma
Tanya Onushko, Gordhan Mahtani, Gabrielle Brazg, T George Hornby, Brian D Schmit
The purpose of this study was to understand how high and low intensity locomotor training (LT) affects sympathetic-somatomotor coupling in people with incomplete spinal cord injury (SCI). Proper coupling between sympathetic and somatomotor systems allows controlled regulation of cardiovascular responses to exercise. In people with SCI, altered connectivity between descending pathways and spinal segments impairs sympathetic and somatomotor coordination, which may have deleterious effects during exercise and limit rehabilitation outcomes...
January 30, 2019: Journal of Neurotrauma
Douglas Brungart, Sarah E Kruger, Tricia Jane Kwiatkowski, Thomas A Heil, Krista B Highland, Julie Cohen, Melissa J Kokx-Ryan, Jaclyn R Schurman, Ashley C Zaleski-King, Danielle J Zion
Service members (SMs) who have suffered mild traumatic brain injury due to blast exposure (b/TBI) often report post-concussive symptoms consistent with auditory, visual, or vestibular impairments even when they score within the normal range on traditional clinical tests of sensory function. One possible explanation for this discrepancy is that patients who score in the low normal range in more than one sensory modality may be severely impaired in tasks that require multisensory integration. This study evaluated unimodal and multimodal sensory performance in SMs with b/TBI and healthy controls by having them conduct four tasks while walking or standing in an immersive virtual environment: an Auditory Localization task (AL) where they moved a cursor to the perceived location of a sound; a Visual Discrimination task (VD) where they distinguished between two visual targets; an Aurally-Aided Visual Search Task (AAVS) where they used an auditory cue to locate and identify a visual target hidden in a field of visual distractors; and a Visual-Only Visual Search task (VOVS) where they located and identified a visual target in a field of distractors with no auditory cue...
January 30, 2019: Journal of Neurotrauma
Sushmita Purkayastha, Farzaneh A Sorond, Sydney Lyng, Justin Frantz, Megan N Murphy, Linda S Hynan, Tonia Sabo, Kathleen Bell
Traumatic brain injury (TBI) is associated with increased risk of later-life neurodegeneration and dementia. However, the underpinning mechanisms are poorly understood and secondary injury resulting from perturbed physiological processes play a significant role. Cerebral vasoreactivity (CVR), a measure of hemodynamic reserve, is known to be impaired in TBI. However, the temporal course of this physiological perturbation is not established. We examined CVR and clinical symptoms on day-3 (T1), day-21 (T2), and day-90 (T3) following concussion in collegiate athletes and cross-sectionally in non-injured controls...
January 29, 2019: Journal of Neurotrauma
Yingli Jing, Degang Yang, Fan Bai, Chao Zhang, Chuan Qin, Di Li, Limiao Wang, Mingliang Yang, Zhi'guo Chen, Jianjun Li
Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction in multiple organs/tissues, such as the gastrointestinal (GI) system. The neuroprotective effects of melatonin in SCI models have been reported; however, it is unclear whether the beneficial effects of melatonin are associated with alleviation of gut dysbiosis. In this study, we showed that daily intraperitoneal injection with melatonin following spinal cord contusion at thoracic level 10 in mice improved intestinal barrier integrity and GI motility, reduced the expression levels of certain pro-inflammatory cytokines, improved animal weight gain and metabolic profiling, and promoted locomotor recovery...
January 29, 2019: Journal of Neurotrauma
Michele Scandola, Luca Dodoni, Giovanna Lazzeri, Carlo Alberto Arcangeli, Renato Avesani, Valentina Moro, Silvio Ionta
Spinal cord injury (SCI) interrupts the brain-body input-output exchange and modifies the mental representation of disconnected body parts, with decreased reliance on sensorimotor aspects of body representation and increased weighting of visuospatial ones. We hypothesized that physiotherapy-related benefits might extend to the re-establishment of the typical interplay between these two types of strategies. To test this hypothesis, we asked 42 participants (21 individuals with SCI pre- and post-physiotherapy, plus 21 controls) to perform mental rotation of corporal images (a cognitive task than can activate one or the other strategy)...
January 29, 2019: Journal of Neurotrauma
Katharina Kohler, Sridhar Nallapareddy, Ari Ercole
Cerebral oxygen delivery is central to the modern intensive care of patients with severe traumatic brain injury. Low brain tissue oxygen tension (P<sub>bt</sub>O<sub>2</sub>) results from microvascular collapse and diffusion limitation and is associated with adverse outcome. A number of therapies to improve oxygen delivery are known to be effective in improving P<sub>bt</sub>O<sub>2</sub>. However their relative effectiveness and microscopic regions of hypoxia may exist/persist even in the presence of normal P<sub>bt</sub>O<sub>2</sub>...
January 28, 2019: Journal of Neurotrauma
Daniel P Holschneider, Yumei Guo, Zhuo Wang, Milagros Vidal, Oscar Umberto Scremin
We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic positive allosteric modulator, for improving memory and motor dysfunction following cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. BQCA (5, 10, 20mg/kg, i.p.x2/day x 3-4 weeks) or vehicle (Veh) were administered, and weekly evaluations undertaken using a battery of motor tests, as well as the Morris Water Maze. Thereafter, cerebral metabolic activation was investigated in awake animals during walking with [<sup>14</sup>C]-2-deoxygIucose autoradiography, comparing CCI mice previously treated with BQCA (20 mg/kg) or vehicle...
January 28, 2019: Journal of Neurotrauma
Christine M Baugh, William Meehan, Emily Kroshus, Thomas G McGuire, Laura A Hatfield
Athletes sometimes choose not to report suspected concussions, risking delays in treatment and health consequences. How and why do athletes make these reporting decisions? Using original survey data from a cohort of college football players, we evaluate two assumptions of the current literature on injury reporting. First, that the probability of reporting a concussion or injury is constant over time. Second, that athletes make reasoned deliberative decisions about whether to report their concussion or other injury...
January 28, 2019: Journal of Neurotrauma
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