Abstract:
:Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C-terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Browning M,Shear DA,Bramlett HM,Dixon CE,Mondello S,Schmid KE,Poloyac SM,Dietrich WD,Hayes RL,Wang KK,Povlishock JT,Tortella FC,Kochanek PMdoi
10.1089/neu.2015.4131subject
Has Abstractpub_date
2016-03-15 00:00:00pages
581-94issue
6eissn
0897-7151issn
1557-9042journal_volume
33pub_type
杂志文章abstract::Spinal cord injury (SCI) can cause physical disability and psychological distress; however, whether SCI is a risk factor for dementia is unclear. This study evaluated the incidence of dementia in patients with SCI. Study participants were recruited from a nationwide cohort during 2004-2007 and categorized into SCI (pa...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4525
更新日期:2017-02-01 00:00:00
abstract::This study characterizes the histological and immunohistochemical changes in the adult rat spinal cord following photochemically induced spinal cord lesions. The spinal cord was exposed by laminectomy (T12-L1 vertebrae) and bathed with 1.5% rose bengal solution for 10 min. The excess dye was removed by saline rinse an...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771503765355559
更新日期:2003-05-01 00:00:00
abstract::Pediatric traumatic brain injury (TBI) research depends on comparisons of profiles and outcomes between brain-injured individuals and groups consisting either of injured controls (e.g., orthopedic injuries, OI) or uninjured, typically developing children recruited from the community (community controls, CC). Children ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4868
更新日期:2017-09-01 00:00:00
abstract::Laser Doppler flowmetry (LDF) was used to study acute ipsilateral and contralateral disturbances of regional cerebral blood flow (rCBF) in a rat model of cerebral cortical contusion trauma. Twelve rats were intubated and artificially ventilated during and after trauma. Injury was produced with a weight drop technique ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1996.13.201
更新日期:1996-04-01 00:00:00
abstract::Outcome following traumatic brain injury (TBI) is not only dependent on the nature and severity of injury and subsequent treatment, but also on constituent characteristics of injured individuals. We aimed to describe and quantify the relationship between demographic characteristics and six month outcome assessed by th...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.0028
更新日期:2007-02-01 00:00:00
abstract::The rat hippocampus is hypersensitive to secondary cerebral ischemia after mild traumatic brain injury (TBI). An unconfirmed assumption in previous studies of mild TBI followed by forebrain ischemia has been that antecedent TBI did not alter cerebral blood flow (CBF) dynamics in response to secondary ischemia. Using l...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1998.15.615
更新日期:1998-08-01 00:00:00
abstract::Clinical studies have documented the importance of secondary brain insults in determining neurologic outcome after head injury. Delayed intracranial hematomas are one of the most easily remediable causes of secondary injury if identified early, but can cause significant disability or death if not promptly recognized a...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.1995.12.591
更新日期:1995-08-01 00:00:00
abstract::The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) m...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1089/neu.2016.4472
更新日期:2018-01-01 00:00:00
abstract::This report is a feasibility study on the utility of gel-free proteomics in identifying peripheral biomarkers of brain injury. The study was performed in six pediatric patients admitted to the intensive care unit for severe traumatic brain injury (TBI). Serum samples collected at admission (less than 8 h after injury)...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.0079
更新日期:2007-01-01 00:00:00
abstract::Studies measuring the volume of infarcted tissue and survival after pharmacologic intervention in stroke are complicated by the potential effect of survival time on infarct volume. In this study, the volume of infarcted tissue as defined by 2,3,5-triphenyltetrazolium chloride staining was determined in rabbits at 28 h...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1996.13.583
更新日期:1996-10-01 00:00:00
abstract::A penetrating traumatic brain injury (pTBI) occurs when an object impacts the head with sufficient force to penetrate the skin, skull, and meninges, and inflict injury directly to the brain parenchyma. This type of injury has been notoriously difficult to model in small laboratory animals such as rats or mice. To this...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.2182
更新日期:2012-04-10 00:00:00
abstract::We investigated the activation of lower limb motor pools by supraspinal and spinal networks after human spinal cord injury (SCI). We compared electromyographic (EMG) activity from six muscles during voluntarily attempted non-weight-bearing single-joint movements, multijoint movements approximating stepping in a supine...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150260338010
更新日期:2002-10-01 00:00:00
abstract::After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4343
更新日期:2017-01-01 00:00:00
abstract::Recovery of fine motor skills after traumatic brain injury (TBI) is variable, with some patients showing progressive improvements over time while others show poor recovery. We therefore studied possible cellular mechanisms accompanying the recovery process in a non-human primate model system, in which the lateral fron...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2009.0966
更新日期:2010-03-01 00:00:00
abstract::Since free radicals play a role in the mechanisms of brain injury after hemorrhagic stroke, the effect of melatonin (a potent antioxidant and free-radical scavenger) on outcomes was investigated after intracerebral hemorrhage (ICH) in rats. ICH was induced by clostridial collagenase infusion into the right caudate put...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2009.1163
更新日期:2010-03-01 00:00:00
abstract::The neuroprotective effects of 17 beta -estradiol have been shown in models of central nervous system injury, including ischemia, brain injury, and more recently, spinal cord injury (SCI). Recent epidemiological trends suggest that SCIs in elderly women are increasing; however, the effects of menopause on estrogen-med...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.830
更新日期:2006-06-01 00:00:00
abstract::Traumatic brain injury (TBI) affects millions of individuals each year and is a leading cause of death and disability worldwide. TBI is heterogeneous and outcome is influenced by a combination of factors that include injury location, severity, genetics, and environmental factors. More recently, sex as a biological var...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2020.7230
更新日期:2020-12-01 00:00:00
abstract::The mechanism by which mechanical impact to brain tissue is transduced to neuronal impairment remains poorly understood. Using an in vitro model of neuronal stretch, we found that mechanical stretch of neurons resulted in a transient plasma membrane permeability increase. Primary cortical neurons, seeded on silicone s...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771503770195885
更新日期:2003-10-01 00:00:00
abstract::Alterations in glutamatergic transmission are thought to contribute to secondary neuronal damage following traumatic brain injury. Using an in vitro cell injury model, we previously demonstrated an apparent reduction in AMPA receptor desensitization and resultant potentiation of AMPA-evoked currents after stretch inju...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/0897715041269704
更新日期:2004-06-01 00:00:00
abstract::Traumatic brain injury (TBI) can trigger disturbances of cerebral pressure autoregulation that can translate into the generation of secondary insults and increased morbidity/mortality. Few therapies have been developed to attenuate the damaging consequences of disturbed autoregulatory control, although some suggest th...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.2278
更新日期:2012-05-01 00:00:00
abstract::Considerable effort and resources have been devoted to preserving life in patients with severe closed traumatic brain injury (TBI). We sought to identify temporal trends in mortality rates of these patients from the late 1800s to the present. We searched the literature for articles on severe TBI, abstracting numbers o...
journal_title:Journal of neurotrauma
pub_type: 历史文章,杂志文章,评审
doi:10.1089/neu.2009.1206
更新日期:2010-07-01 00:00:00
abstract::Persistent post-traumatic headache (PPTH) is often the most common injury after mild traumatic brain injury (mTBI), reported by 47-95% of patients. Progressive muscle relaxation (PMR) has level A evidence in preventing migraine and tension headaches. However, research on this behavioral therapy for PPTH, let alone sma...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6601
更新日期:2021-01-01 00:00:00
abstract::Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumonia, suggesting a sp...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.3060
更新日期:2013-12-15 00:00:00
abstract::After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-th...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2020.7504
更新日期:2021-01-04 00:00:00
abstract::The purpose of this study was to evaluate the effects of posttraumatic hyperglycemia on contusion volume and neutrophil accumulation following moderate traumatic brain injury (TBI) in rats. A parasagittal fluid-percussion (F-P) brain injury (1.8-2.1 atm) was induced in male Sprague-Dawley rats. Rats were then randomiz...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150260139075
更新日期:2002-06-01 00:00:00
abstract::Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organized inflammatory response to injury. Intricate immune cell interactions are triggered, typically co...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.2014.3429
更新日期:2014-11-01 00:00:00
abstract::Acute subdural hemorrhage (ASDH) is common and associated with severe morbidity and mortality. To date, the role of spontaneous cortical spreading depression (sCSD) in exaggerating secondary injury after ASDH, is poorly understood. The present study contains two experimental groups: First, we investigated and characte...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5657
更新日期:2019-01-15 00:00:00
abstract::Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. The study objective was to assess whether biomarkers concentrations obtained at the time of injury are associated with outcome. Serial serum concentrations of neur...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2007.0316
更新日期:2007-12-01 00:00:00
abstract::Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.2916
更新日期:2014-02-15 00:00:00
abstract::Guidelines for patients with severe traumatic brain injury (sTBI) published in 2007 recommend providing early nutrition after trauma. Early enteral nutrition (EN) started within 48 h post-injury reduces clinical malnutrition, prevents bacterial translocation from the gastrointestinal tract, and improves outcome in sTB...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,多中心研究
doi:10.1089/neu.2011.1801
更新日期:2012-01-01 00:00:00