Journal of Neurotrauma (J NEUROTRAUM)

Publications in this journal

• Article: 3. M. Skotak, F. Wang, A. Alai, A. Holmberg, H. Seth, R. Switzer III, and N. Chandra, Rat Injury Model Under Controlled Field-Relevant Primary Blast Conditions: Acute Response to a Wide Range of Peak Overpressure, Journal of Neurotrauma, (in print, 2013)

  M. Skotak, F. Wang, A. Alai, A. Holmberg, H. Seth, R. Switzer III, N. Chandra
  Journal of Neurotrauma 01/2013;
• Article: Whole-body vibration improves functional recovery in spinal cord-injured rats.

  Wirth F, Schempf G, Stein G, Wellmann K, Manthou M, Scholl C, Sidorenko M, Semler J, Eisel L, Harrach R, [......], Ankerne J, Ashrafi M, Ozsoy O, Ozsoy U, Schubert H, Abdulla D, Dunlop S, Angelov DN, Irintchev A, Schoenau E
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  ABSTRACT: Whole-body vibration (WBV) is a relatively novel form of exercise used to improve neuromuscular performance in healthy individuals. Its usefulness as a therapy for patients with neurological disorders, in particular spinal cord injury (SCI), has received little attention in clinical settings and, surprisingly, even less in animal SCI models. We performed severe compression SCI at a low-thoracic level in Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10 rats) served as controls. Compared to sham treated rats, WBV did not improve BBB score, plantar stepping or ladder stepping during the 12-week period. Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume, serotonergic input to the lumbar spinal cord nor cholinergic or glutamatergic inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham, WBV14, but not WBV7, significantly improved body weight support (rump-height index) during overground locomotion and overall recovery between 6 - 12 weeks and also restored the density of synaptic terminals in the lumbar spinal cord at 12 weeks. Most remarkably, WBV14 lead to a significant improvement of bladder function at 6 - 12 weeks after injury. These findings provide the first evidence for functional benefits of WBV in an animal SCI model and warrant further preclinical investigations to determine mechanisms underpinning this non-invasive, inexpensive and easily delivered potential rehabilitation therapy for SCI.
  Journal of Neurotrauma 11/2012;
• Article: Upregulation of RyR-2 in hypoxic/reperfusion injury.

  Varun Kesherwani, S.K. Agrawal
  Journal of Neurotrauma 06/2012; PMID 21612318(6):1255-1265.
• Article: 7. A. Sundaramurthy, A .Alai, ,S. Ganpule, A. Holmberg, E. Plougonven and N. Chandra, Blast-Induced Biomechanical Loading of the Rat: An Experimental and Anatomically Accurate Computational Blast Injury Model, Journal of Neurotrauma, 29, 13, 2352-2364, DOI: 10.1089/neu.2012.2413, (July 2012

  A. Sundaramurthy, A .Alai, S. Ganpule, A. Holmberg, E. Plougonven, N. Chandra
  Journal of Neurotrauma 01/2012; 29(13):2352-2364.
• Article: Lasting pituitary hormone deficiency after traumatic brain injury

  Kozlowski Moreau O, Yollin E, Merlen E, Daveluy W, Rousseaux M
  Journal of Neurotrauma 01/2012; 29:81-89.
• Article: Acute bisperoxovanadium therapy stimulates Akt and mTOR activity, reduces autophagy, and promotes neuroprotection and functional recovery following cervical contusive spinal cord injury

  CL Walker, Xu Walker MJ, XM
  Journal of Neurotrauma 01/2011; 28:A-1-A-134.
• Article: Blast-induced traumatic brain injury and polytrauma--a critical problem begging for new insight and new therapies.

  Patrick Michael Kochanek, Richard A Bauman, Joseph Long, C Edward Dixon, Larry W Jenkins
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  ABSTRACT: Foreword for the blast-induced TBI supplement.
  Journal of Neurotrauma 03/2009;
• Article: Apolipoprotein E4 as a Predictor of Outcomes in Pediatric Mild Traumatic Brain Injury.

  Lisa M Moran, H Gerry Taylor, Kalaichelvi Ganesaligam, Julie M Gastier-Foster, Jessica Frick, Barbara Bangert, Ann Dietrich, Kathryn E Nuss, Jerome Rusin, Martha Wright, Keith O Yeates
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  ABSTRACT: The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.
  Journal of Neurotrauma 03/2009;
• Article: Magnetic Resonance Imaging Assessment of Macrophage Accumulation in Mouse Brain after Experimental Traumatic Brain Injury.

  Lesley May Foley, T Kevin Hitchens, Chien Ho, Keri L Janesko, John A Melick, Hulya Bayir, Patrick Michael Kochanek
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  ABSTRACT: Macrophages contribute to secondary damage and repair after CNS injury. Micron-sized paramagnetic iron oxide (MPIO) particles can label macrophages in situ, facilitating 3D mapping of macrophage accumulation following TBI, via ex vivo magnetic resonance microscopy (MRM) and in vivo monitoring with MR imaging (MRI). MPIO particles were injected iv (4.5 mg Fe/Kg) in male C57BL/6J mice (n=25). A controlled cortical impact (CCI) was delivered to the left parietal cortex. Five protocols were used in naïve and injured mice to assess feasibility, specificity and optimal labeling time. In vivo imaging was carried out at 4.7T. Brains were then excised for 3D MRM at 11.7T. Triple-label immunofluorescence (MPIO via dragon green, macrophages via F480, and nuclei via DAPI) of brain sections confirmed MPIO particles within macrophages. MRM of naïves showed an even distribution of a small number of MPIO-labeled macrophages in the brain. MRM at 48-72 h after CCI and MPIO injection revealed MPIO-labeled macrophages accumulated in the trauma region. When MPIO particles were injected 6 d before CCI, MRM 48 h after CCI also revealed labeled cells at the injury site. In vivo studies of macrophage accumulation by MRI suggest that this approach is feasible, but requires additional optimization. We conclude that MPIO labeling and ex vivo MRM mapping of macrophage accumulation for assessment of TBI is readily accomplished. This new technique could serve as an adjunct to conventional MR approaches by defining inflammatory mechanisms and therapeutic efficacy of anti-inflammatory agents in experimental TBI.
  Journal of Neurotrauma 03/2009;
• Article: The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat.

  Fredrik Clausen, Niklas Marklund, Anders Lewén, Lars Hillered
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  ABSTRACT: Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models of ischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenous infusion of NXY-059 or vehicle was initiated 30 min following a severe lateral fluid percussion brain injury (FPI) in adult rats (n=22), and histological and behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated in the Morris water maze at post-injury days 11-14, followed by a probe trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated protein (MAP)-2 stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatial learning deficits when compared to the brain-injured, vehicle-treated control animals (p < 0.05). NXY-059-treated animals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0 +/- 11 mm3 versus 74.4 +/- 19 mm3, respectively; p < 0.01). The results show that post-injury treatment with NXY-059 significantly attenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role for ROS in the pathophysiology of TBI.
  Journal of Neurotrauma 02/2009; 25(12):1449-57.
• Article: Improvements in orthostatic instability with stand locomotor training in individuals with spinal cord injury.

  Susan J Harkema, Christie K Ferreira, Rubia J van den Brand, Andrei V Krassioukov
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  ABSTRACT: Prospective assessment of cardiovascular control in individuals with spinal cord injury (SCI) in response to active stand training. Cardiovascular parameters were measured at rest and in response to orthostatic challenge before and after training in individuals with clinically complete SCI. The goal of this study was to evaluate the effect of active stand training on arterial blood pressure and heart rate and changes in response to orthostatic stress in individuals with SCI. Measurements were obtained in individuals with SCI (n=8) prior to and after 40 and 80 sessions of the standing component of a locomotor training intervention (stand LT). During standing, all participants wore a harness and were suspended by an overhead, pneumatic body weight support (BWS) system over a treadmill. Trainers provided manual facilitation as necessary at the trunk and legs. All individuals were able to bear more weight on their legs after the stand LT training. Resting arterial blood pressure significantly increased in individuals with cervical SCI after 80 training sessions. At the end of the training period, resting systolic blood pressure (BP) in individuals with cervical SCI in a seated position, increased by 24% (from 84 +/- 5 to 104 +/- 7 mmHg). Furthermore, orthostatic hypotension present in response to standing prior to training (decrease in systolic BP of 24 +/- 14 mmHg) was not evident (decrease in systolic BP of 0 +/- 11 mmHg) after 80 sessions of stand LT. Hemodynamic parameters of individuals with thoracic SCI were relatively stable prior to training and not significantly different after 80 sessions of stand LT. Improvements in resting arterial blood pressure and responses to orthostatic stress in individuals with clinically complete cervical SCI occurred following intensive stand LT training. These results may be attributed to repetitive neuromuscular activation of the legs from loading and/or conditioning of cardiovascular responses from repetitively assuming an upright posture.
  Journal of Neurotrauma 02/2009; 25(12):1467-75.
• Article: Pathology dynamics predict spinal cord injury therapeutic success.

  Cassie S Mitchell, Robert H Lee
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  ABSTRACT: Secondary injury, the complex cascade of cellular events following spinal cord injury (SCI), is a major source of post-insult neuron death. Experimental work has focused on the details of individual factors or mechanisms that contribute to secondary injury, but little is known about the interactions among factors leading to the overall pathology dynamics that underlie its propagation. Prior hypotheses suggest that the pathology is dominated by interactions, with therapeutic success lying in combinations of neuroprotective treatments. In this study, we provide the first comprehensive, system-level characterization of the entire secondary injury process using a novel relational model methodology that aggregates the findings of approximately 250 experimental studies. Our quantitative examination of the overall pathology dynamics suggests that, while the pathology is initially dominated by "fire-like", rate-dependent interactions, it quickly switches to a "flood-like", accumulation-dependent process with contributing factors being largely independent. Our evaluation of approximately 20,000 potential single and combinatorial treatments indicates this flood-like pathology results in few highly influential factors at clinically realistic treatment time frames, with multi-factor treatments being merely additive rather than synergistic in reducing neuron death. Our findings give new fundamental insight into the understanding of the secondary injury pathology as a whole, provide direction for alternative therapeutic strategies, and suggest that ultimate success in treating SCI lies in the pursuit of pathology dynamics in addition to individually involved factors.
  Journal of Neurotrauma 02/2009; 25(12):1483-97.
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  Available from: csccm.org.cn

  Article: Hypermetabolism following moderate to severe traumatic acute brain injury: a systematic review.

  Norine Foley, Shawn Marshall, Jill Pikul, Katherine Salter, Robert Teasell
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  ABSTRACT: Elevations of metabolic rate following traumatic brain injury (TBI) have been reported previously, with estimates ranging from 32% to 200% above normal values. The aim of this systematic review was to describe the pattern of energy expenditure during the first 30 days following TBI. We searched six databases for trials that measured the energy expenditure at least once during the first 30 days post-injury and compared that value to one that would be predicted in the non-injured state. We identified 24 studies, three of which were randomized controlled trials (RCTs). The sample sizes of the included studies ranged from 6 to 80 (mean, 24.7), and the mean Glasgow Coma Scale (GCS) score of subjects was 4.8. Mean energy expenditure, expressed as a percentage of a predicted value, ranged from 75% to 200%. The lowest values were reported in patients admitted in brain death. Several factors were found to have modulating effects on energy expenditure. The administration of paralyzing agents, sedatives, or barbiturates reduced metabolic rate by approximately 12-32%. Propranolol and morphine were associated with smaller decreases in energy expenditure. Factors that do not appear to augment the hypermetabolic response included the administration of steroids and method of feeding (enteral vs. parenteral). Based on our results, it was unclear if elevated temperature, the presence of extracranial injury, or the severity of injury further exacerbate hypermetabolism. We conclude that energy expenditure following TBI is highly variable, and the use of standard factors to estimate the energy needs of individual patients are inappropriate and should be discouraged.
  Journal of Neurotrauma 02/2009; 25(12):1415-31.
• Article: Neuropathology and pressure in the pig brain resulting from low-impulse noise exposure.

  Annette Säljö, Fredrik Arrhén, Hayde Bolouri, Maria Mayorga, Anders Hamberger
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  ABSTRACT: Military personnel are exposed to occupational levels of blast overpressure during training. This study characterizes the pressure-time histories of air, underwater, and localized blast, and correlates blast parameters with neuropathology. Blast overpressure was produced by a howitzer, a bazooka, an automatic rifle, underwater explosives, or a shock tube. Anesthetized pigs were exposed in positions that simulated real training scenarios. Underwater exposures were performed using explosives at distances recommended by safety requirements. In other experiments, rats were exposed via a shock tube. The pressure changes were recorded with a hydrophone sensor in the brain of the pig and in rats with an optical fiber sensor. Histological examination of porcine brains revealed small parenchymal and subarachnoid hemorrhages, predominately in the occipital lobe, cerebellum, and medulla oblongata. Relative to the peak pressure in air, that in porcine brain (Pmax brain/air) was 0.7 for the bazooka and 0.5 and 0.7, respectively, for the 9- and 30-kPa howitzer. The attenuation was stronger in water: the detonation pulse had a brain/water ratio of 0.1, and the secondary pulses had ratios of 0.3-0.4. The results indicate that low-frequency spectra penetrate easily from air or water into the brain, but high-frequency spectra appear to be filtered by body structures. In addition, blast waves were recorded in the brain and abdomen of pigs after local exposure via shock tube to either the abdomen or the top of the skull. When the abdomen was exposed, the maximal peak value in the brain was only 3% of that in the abdomen. Moreover, part of this pressure could have been derived from the air outside the head. The results gave little support to significant transmission of pressure within the body.
  Journal of Neurotrauma 02/2009; 25(12):1397-406.
• Article: GDNF plasma levels in spina bifida: correlation with severity of spinal damage and motor function.

  Antonio Chiaretti, Claudia Rendeli, Alessia Antonelli, Giuseppe Barone, Benedetta Focarelli, Fabrizia Tabacco, Luca Massimi, Emanuele Ausili
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  ABSTRACT: Glial-derived neurotrophic factor (GDNF) is one of several powerful survival factors for spinal motoneurons that play a key role in sprouting, synaptic plasticity, and reorganization after spinal cord damage. The aim of this study was to investigate the expression of GDNF in plasma of children with spina bifida (SB) and to determine its correlation with both the severity of spinal cord damage and the motor function of these patients. To measure the GDNF expression, we collected plasma samples from 152 children with SB and in 149 matched controls. Endogenous GDNF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. In children with SB the mean levels of GDNF (131.2 +/- 69.6 pg/mL) were significantly higher (p < 0.001) with respect to the mean levels of the control group (102.7 +/- 6.8 pg/mL). Moreover, in open SB, the GDNF levels (139.2 +/- 81.1 pg/mL) were significantly higher (p < 0.05) with respect to closed SB (117.2 +/- 41.3 pg/mL). In terms of the motor function of patients, we found that in children with poorer motor function, the GDNF levels (134.5 +/- 67.4 pg/mL) were higher, but not statistically significant (p < 0.1), than in patients with better motor outcome (122.3 +/- 72.2 pg/mL). Our study demonstrates GDNF over-expression in children with SB. This upregulation is significantly associated with the severity of spinal cord damage in SB patients and appears to correlate with poor motor function of children, representing an important biochemical marker of the severity of spine injury.
  Journal of Neurotrauma 01/2009; 25(12):1477-81.
• Conference Proceeding: NEURAL CORRELATES OF IMPAIRED PERFORMANCE IN A WORKING MEMORY TASK IN SURVIVORS OF TRAUMATIC BRAIN INJURY

  M Kasahara, DK Menon, CH Salmond, JG Outtrim, JVT Tavares, TA Carpenter, BJ Sahakian, EA Stamatakis
  JOURNAL OF NEUROTRAUMA; 01/2009