Abstract:
:Although mechanisms involved in progression of cell death in spinal cord injury (SCI) have been studied extensively, few are clear targets for translation to clinical application. One of the best-understood mechanisms of cell survival in SCI is phosphatidylinositol-3-kinase (PI3K)/Akt and associated downstream signaling. Clear therapeutic efficacy of a phosphatase and tensin homologue (PTEN) inhibitor called bisperoxovanadium (bpV) has been shown in SCI, traumatic brain injury, stroke, and other neurological disease models in both neuroprotection and functional recovery. The present study aimed to elucidate mechanistic influences of bpV activity in neuronal survival in in vitro and in vivo models of SCI. Treatment with 100 nM bpV(pic) reduced cell death in a primary spinal neuron injury model (p < 0.05) in vitro, and upregulated both Akt and ribosomal protein S6 (pS6) activity (p < 0.05) compared with non-treated injured neurons. Pre-treatment of spinal neurons with a PI3K inhibitor, LY294002 or mammalian target of rapamycin (mTOR) inhibitor, rapamycin blocked bpV activation of Akt and ribosomal protein S6 activity, respectively. Treatment with bpV increased extracellular signal-related kinase (Erk) activity after scratch injury in vitro, and rapamycin reduced influence by bpV on Erk phosphorylation. After a cervical hemicontusive SCI, Akt phosphorylation decreased in total tissue via Western blot analysis (p < 0.01) as well as in penumbral ventral horn motor neurons throughout the first week post-injury (p < 0.05). Conversely, PTEN activity appeared to increase over this period. As observed in vitro, bpV also increased Erk activity post-SCI (p < 0.05). Our results suggest that PI3K/Akt signaling is the likely primary mechanism of bpV action in mediating neuroprotection in injured spinal neurons.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Walker CL,Wu X,Liu NK,Xu XMdoi
10.1089/neu.2018.6294subject
Has Abstractpub_date
2019-09-15 00:00:00pages
2676-2687issue
18eissn
0897-7151issn
1557-9042journal_volume
36pub_type
杂志文章abstract::The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoi...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.3887
更新日期:2016-01-15 00:00:00
abstract::Risk factors for head injury are also risk factors for becoming homeless but there is little research on this vulnerable group, who can be neglected by health services that specialize in acquired brain injury. This study investigates the prevalence of admissions to hospital with a head injury in the homeless and assoc...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2014.3387
更新日期:2015-01-15 00:00:00
abstract::There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6471
更新日期:2020-01-01 00:00:00
abstract::The canine double hemorrhage model is an established model to study cerebral vasospasm, the late sequelae of subarachnoid hemorrhage (SAH). The present study uses magnetic resonance imaging (MRI) to examine the recently reported early brain injury after SAH. Double hemorrhage SAH modeling was obtained by injecting 0.5...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2008.0518
更新日期:2008-09-01 00:00:00
abstract::Mild traumatic brain injury (mTBI) accounts for the majority of head trauma cases. Despite some lasting cognitive, emotional, and behavioral deficits, there are frequently no overt morphological defects, suggesting that changes may result from alterations in the physiology of individual neurons. We investigated hippoc...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.2192
更新日期:2012-04-10 00:00:00
abstract::Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umeå, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The pri...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2005.356E
更新日期:2007-06-01 00:00:00
abstract::The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a cont...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2020.7300
更新日期:2020-12-14 00:00:00
abstract::. ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6059
更新日期:2018-08-04 00:00:00
abstract::A retrospective case-control study was undertaken to determine the best technique to measure neural canal encroachment at each lumbar level following burst fracture and its relationship to the presence of neurologic deficit. Only patients with postinjury CT scans demonstrating a disrupted posterior body with a retropu...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1994.11.711
更新日期:1994-12-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is commonly observed in military service members with mild traumatic brain injury (mTBI); however, the relationship between mTBI and PTSD is complex and not well understood. The present study aims to elucidate a link between the degree of alteration in limbic system-related white ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5541
更新日期:2019-04-01 00:00:00
abstract::It is now generally accepted that excitotoxic cell death involves bioenergetic failure resulting from the cycling of Ca2+ and the generation of reactive oxygen species (ROS) by mitochondria. Both Ca2+ cycling and ROS formation by mitochondria are dependent on the mitochondrial membrane potential (Deltapsi(m)) that res...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2005.22.1142
更新日期:2005-10-01 00:00:00
abstract::Axon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regenerati...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5966
更新日期:2019-06-15 00:00:00
abstract::Delirium is a commonly reported acute care adverse event in patients with traumatic spinal cord injury (TSCI), but studies specifically investigating it in this population are lacking. The purpose of this study was to characterize the onset, risk factors, and impact of delirium in patients with TSCI. Patients discharg...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.2975
更新日期:2013-11-01 00:00:00
abstract::Anatomical studies of spinal cord injury (SCI) using magnetic resonance imaging (MRI) report diverging observations, from "no changes" to "tissue atrophy in motor and non-motor regions." These discrepancies among studies can be attributed to heterogeneity in extent, level, and post-injury duration observed within the ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6040
更新日期:2019-06-15 00:00:00
abstract::This study created a framework incorporating provider perspectives of best practices for early psychosocial intervention to improve caregiver experiences and outcomes after severe pediatric traumatic brain injury (TBI). A purposive sample of 23 healthcare providers from the emergency, intensive care, and acute care de...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2020.7323
更新日期:2020-11-09 00:00:00
abstract::There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would ...
journal_title:Journal of neurotrauma
pub_type: 临床试验,杂志文章
doi:10.1089/neu.2009.1080
更新日期:2010-04-01 00:00:00
abstract::Post-traumatic epilepsy (PTE) is a consequence of traumatic brain injury (TBI), occurring in 10-25% of patients with moderate to severe injuries. The development of animal models for testing antiepileptogenic therapies and validation of biomarkers to follow epileptogenesis in humans necessitates sophisticated understa...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.3221
更新日期:2014-08-15 00:00:00
abstract::Spinal cord injury (SCI) is a devastating condition affecting young, healthy individuals worldwide. Existing agents have inadequate therapeutic efficacy, and some are associated with side effects. Our objective is to summarize and critically assess the neurological recovery and antioxidant effects of curcumin for trea...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,meta分析,评审
doi:10.1089/neu.2014.3520
更新日期:2015-03-15 00:00:00
abstract::Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inh...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5049
更新日期:2018-02-15 00:00:00
abstract::Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. Previously published studies evaluating the ability of serum biomarkers to predict outcome after pediatric TBI have focused on three markers: neuron-specific enola...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.1989
更新日期:2012-01-01 00:00:00
abstract::Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150152693728
更新日期:2001-10-01 00:00:00
abstract::Rodent models of spinal cord injury are critical for the development of treatments for upper limb motor impairment in humans, but there are few methods for measuring forelimb strength of rodents, an important outcome measure. We developed a novel robotic device--the Robotic Rehabilitator of the Rodent Upper Extremity ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.3987
更新日期:2016-03-01 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::Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutr...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2009.1255
更新日期:2010-07-01 00:00:00
abstract::The aim of this study is to assess the utility and effectiveness of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) of the entire pediatric cervical and thoracic spinal cord toward discrimination of typically developing (TD) controls and subjects with spinal cord injury (SCI). A total of 43 pedi...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5174
更新日期:2018-02-01 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::It remains unclear whether the benefits of early surgical timing are significant in neurologically complete spinal cord injury (SCI). We wanted to compare the effects of early and late surgical timing on non-neurological outcomes in persons with traumatic complete SCI. All cases of traumatic complete SCI referred to a...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.2957
更新日期:2013-09-15 00:00:00
abstract::Over the last decade, biomarker research has identified potential biomarkers for the diagnosis, prognosis, and management of traumatic brain injury (TBI). Several cerebrospinal fluid (CSF) and serum biomarkers have shown promise in predicting long-term outcome after severe TBI. Despite this increased focus on identify...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2012.2578
更新日期:2013-06-01 00:00:00
abstract::Optic nerve crush injury leads to death of retinal ganglion cells (RGCs), both as a direct result of the primary injury and via secondary degeneration induced by neurotoxins secreted by dying RGCs. Studies have shown that, if optic nerve crush is preceded by an unrelated injury to another part of the central nervous s...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.1072
更新日期:2006-07-01 00:00:00
abstract::4-Aminopyridine (4AP), a potassium channel antagonist, can improve hindlimb motor function in dogs with chronic thoracolumbar spinal cord injury (SCI); however, individual response is variable. We hypothesized that injury characteristics would differ between dogs that do and do not respond to 4AP. Our objective was to...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5975
更新日期:2019-05-01 00:00:00