Activating Transcription Factor-6α Deletion Modulates the Endoplasmic Reticulum Stress Response after Spinal Cord Injury but Does Not Affect Locomotor Recovery.

Abstract:

:The endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases. We recently demonstrated improvements in hindlimb locomotion after thoracic spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism using genetic and pharmacological inhibition of the protein kinase ribonucleic acid-like ER kinase- CCAAT/enhancer binding homologous protein (PERK-CHOP) arm of the ERSR. Here, we investigated the contribution of activating transcription factor-6 (ATF6), an ERSR signaling effector comprising the second arm of ERSR, in the pathogenesis of SCI. In contrast to what was seen after attenuation of PERK-CHOP signaling, genetic ablation of ATF6 results in modulation of ERSR and decreased survival in oligodendrocyte precursor cells against ER stress. Further, ATF6 loss delays the ERSR after SCI, potentiates PERK-ATF4-CHOP signaling and fails to improve locomotor deficits. These data suggest that deleting ATF6 levels is unlikely to be a viable therapeutic target to improve functional recovery after SCI.

journal_name

J Neurotrauma

journal_title

Journal of neurotrauma

authors

Saraswat Ohri S,Mullins A,Hetman M,Whittemore SR

doi

10.1089/neu.2015.3993

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

486-491

issue

3

eissn

0897-7151

issn

1557-9042

journal_volume

35

pub_type

杂志文章
  • Glucocorticoid receptor and mitogen-activated protein kinase activity after restraint stress and acoustic trauma.

    abstract::Restraint stress (RS) protects auditory function against acoustic trauma by activating glucocorticoid receptors (GR) in the cochlea. In a search for the signaling pathways downstream to GR that may be involved in RS-induced protection we report here (1) a downregulation of phosphorylated extracellular signal-regulated...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2008.0874

    authors: Meltser I,Tahera Y,Canlon B

    更新日期:2009-10-01 00:00:00

  • Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head.

    abstract::Rotational acceleration of the head, as occurs in falls, car crashes, and sport injuries, may result in diffuse brain damage, with acute and chronic neurological and psychiatric symptoms. The present study addresses the effects of rotational trauma on the neuronal cytoskeleton, which stabilizes perikaryal, dendritic a...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/08977150360547080

    authors: Hamberger A,Huang YL,Zhu H,Bao F,Ding M,Blennow K,Olsson A,Hansson HA,Viano D,Haglid KG

    更新日期:2003-02-01 00:00:00

  • Spectral analyses of cardiovascular control in rodents with spinal cord injury.

    abstract::The severity of injury to cardiovascular autonomic pathways following clinical spinal cord injury (SCI) can be evaluated with spectral analyses. Whether this technique provides a translatable assessment of cardiovascular autonomic function in rodent SCI is unknown. Beat-to-beat blood pressure and pulse interval were m...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2011.2145

    authors: Inskip JA,Ramer LM,Ramer MS,Krassioukov AV,Claydon VE

    更新日期:2012-05-20 00:00:00

  • Standardizing data collection in traumatic brain injury.

    abstract::Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we "speak the same language." Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons betwe...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2010.1617

    authors: Maas AI,Harrison-Felix CL,Menon D,Adelson PD,Balkin T,Bullock R,Engel DC,Gordon W,Langlois-Orman J,Lew HL,Robertson C,Temkin N,Valadka A,Verfaellie M,Wainwright M,Wright DW,Schwab K

    更新日期:2011-02-01 00:00:00

  • Differential Gene Expression Associated with Meningeal Injury in Acute Mild Traumatic Brain Injury.

    abstract::Injury to the meninges is not uncommon after traumatic brain injury (TBI), yet minimal research has been directed toward understanding the relevant biology. After a concussive event, the meninges are observed to abnormally enhance on post-contrast magnetic resonance imaging (MRI) in some patients, but not all. The aim...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2016.4479

    authors: Livingston WS,Gill JM,Cota MR,Olivera A,O'Keefe JL,Martin C,Latour LL

    更新日期:2017-02-15 00:00:00

  • Uncontrollable stimulation undermines recovery after spinal cord injury.

    abstract::Prior studies have shown that neurons within the spinal cord are sensitive to response-outcome relations, a form of instrumental learning. Spinally transected rats that receive shock to one hind leg learn to maintain the leg in a flexed position that minimizes net shock exposure (controllable shock). Prior exposure to...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2004.21.1795

    authors: Grau JW,Washburn SN,Hook MA,Ferguson AR,Crown ED,Garcia G,Bolding KA,Miranda RC

    更新日期:2004-12-01 00:00:00

  • Protective effect of melatonin upon neuropathology, striatal function, and memory ability after intracerebral hemorrhage in rats.

    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

    authors: Lekic T,Hartman R,Rojas H,Manaenko A,Chen W,Ayer R,Tang J,Zhang JH

    更新日期:2010-03-01 00:00:00

  • The Evolution of Post-Traumatic Stress Disorder following Moderate-to-Severe Traumatic Brain Injury.

    abstract::Increasing evidence indicates that post-traumatic stress disorder (PTSD) may develop following traumatic brain injury (TBI), despite most patients having no conscious memory of their accident. This prospective study examined the frequency, timing of onset, symptom profile, and trajectory of PTSD and its psychiatric co...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2015.3992

    authors: Alway Y,Gould KR,McKay A,Johnston L,Ponsford J

    更新日期:2016-05-01 00:00:00

  • Modeling of Community Integration Trajectories in the First Five Years after Traumatic Brain Injury.

    abstract::The aims of this study were to assess the trajectories of community integration in individuals with traumatic brain injury (TBI) through one, two, and five years post-injury and to examine whether those trajectories could be predicted by demographic and injury characteristics. A longitudinal cohort study was conducted...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2014.3844

    authors: Andelic N,Arango-Lasprilla JC,Perrin PB,Sigurdardottir S,Lu J,Landa LO,Forslund MV,Roe C

    更新日期:2016-01-01 00:00:00

  • A novel animal model of closed-head concussive-induced mild traumatic brain injury: development, implementation, and characterization.

    abstract::Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). While single concussions result in short-term neurologic dysfunction, multiple concussions can result in cumulative damage and increased risk for neurodegenerative disease. Despite the prevalence of concussion, knowledge ab...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2011.2057

    authors: Chen Z,Leung LY,Mountney A,Liao Z,Yang W,Lu XC,Dave J,Deng-Bryant Y,Wei G,Schmid K,Shear DA,Tortella FC

    更新日期:2012-01-20 00:00:00

  • Neutrophils do not mediate blood-brain barrier permeability early after controlled cortical impact in rats.

    abstract::Controlled cortical impact (CCI) produces blood-brain barrier (BBB) permeability and an acute inflammatory response in injured brain, associated with upregulation of cell adhesion molecules and accumulation of neutrophils. Nevertheless, the role of acute inflammation in the pathogenesis of BBB permeability after traum...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1999.16.583

    authors: Whalen MJ,Carlos TM,Kochanek PM,Clark RS,Heineman S,Schiding JK,Franicola D,Memarzadeh F,Lo W,Marion DW,Dekosky ST

    更新日期:1999-07-01 00:00:00

  • An oligomeric diet limits the response to injury in traumatic brain-injured rats.

    abstract::Adequate nutritional support is a major challenge in brain injury patients, because malnutrition cannot be reversed by standard enteral nutrition. We hypothesized that an oligomeric formula could improve nutritional status by restoring intestinal trophicity. Eighteen male Sprague-Dawley rats (300-330 g) underwent gast...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2012.2707

    authors: Moinard C,Delpierre E,Loï C,Neveux N,Butel MJ,Cynober L,Charrueau C

    更新日期:2013-06-01 00:00:00

  • Altered NO function contributes to impairment of uPA and tPA cerebrovasodilation after brain injury.

    abstract::Urokinase (uPA) and tissue plasminogen activator (tPA) are serine proteases implicated in fibrinolysis, but their role in the regulation of the cerebrovascular response to brain trauma has not been investigated. This study was designed to (1) characterize the cerebrovascular activity of uPA and tPA, (2) investigate th...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2004.21.1204

    authors: Armstead WM,Cines DB,Al-Roof Higazi A

    更新日期:2004-09-01 00:00:00

  • Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions.

    abstract::Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1998.15.199

    authors: Lindner MD,Plone MA,Cain CK,Frydel B,Francis JM,Emerich DF,Sutton RL

    更新日期:1998-03-01 00:00:00

  • Head injury and mortality in the homeless.

    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

    authors: McMillan TM,Laurie M,Oddy M,Menzies M,Stewart E,Wainman-Lefley J

    更新日期:2015-01-15 00:00:00

  • Effect of blast exposure on the brain structure and cognition in Macaca fascicularis.

    abstract::Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated th...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2010.1591

    authors: Lu J,Ng KC,Ling G,Wu J,Poon DJ,Kan EM,Tan MH,Wu YJ,Li P,Moochhala S,Yap E,Lee LK,Teo M,Yeh IB,Sergio DM,Chua F,Kumar SD,Ling EA

    更新日期:2012-05-01 00:00:00

  • Time- and dose-dependent neuroprotective effects of sex steroid hormones on inflammatory cytokines after a traumatic brain injury.

    abstract::Following a traumatic brain injury (TBI), excessive release of proinflammatory cytokines is the major cause of cerebral edema and neuronal loss. This study was designed to examine changes in concentrations of some proinflammatory cytokines-including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis fact...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2010.1686

    authors: Sarkaki AR,Khaksari Haddad M,Soltani Z,Shahrokhi N,Mahmoodi M

    更新日期:2013-01-01 00:00:00

  • The effect of postinjury administration of polyethylene glycol-conjugated superoxide dismutase (pegorgotein, Dismutec) or lidocaine on behavioral function following fluid-percussion brain injury in rats.

    abstract::Previous studies in our laboratory have shown that polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) or lidocaine treatment before experimental fluid-percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to ...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1996.13.325

    authors: Hamm RJ,Temple MD,Pike BR,Ellis EF

    更新日期:1996-06-01 00:00:00

  • Transcriptional Changes in the Mouse Retina after Ocular Blast Injury: A Role for the Immune System.

    abstract::Ocular blast injury is a major medical concern for soldiers and explosion victims due to poor visual outcomes. To define the changes in gene expression following a blast injury to the eye, we examined retinal ribonucleic acid (RNA) expression in 54 mouse strains 5 days after a single 50-psi overpressure air wave blast...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2017.5104

    authors: Struebing FL,King R,Li Y,Chrenek MA,Lyuboslavsky PN,Sidhu CS,Iuvone PM,Geisert EE

    更新日期:2018-01-01 00:00:00

  • White Matter Changes and Confrontation Naming in Retired Aging National Football League Athletes.

    abstract::Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores i...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2016.4446

    authors: Strain JF,Didehbani N,Spence J,Conover H,Bartz EK,Mansinghani S,Jeroudi MK,Rao NK,Fields LM,Kraut MA,Cullum CM,Hart J Jr,Womack KB

    更新日期:2017-01-15 00:00:00

  • Urinary bladder irritation alters efficacy of vagal stimulation on rostral medullary neurons in chronic T8 spinalized rats.

    abstract::The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2007.0276

    authors: Kaddumi EG,Hubscher CH

    更新日期:2007-07-01 00:00:00

  • Safety versus efficacy of spinal cord stimulation for the generation of motor-evoked potentials in the rat.

    abstract::The relative safety and efficacy of direct versus indirect methods of spinal cord stimulation for the production of descending motor-evoked responses was studied in pentobarbital-anesthetized rats (n = 39). Electrical stimuli were delivered for 1 h, either directly to the cord dorsum using silver ball electrodes or in...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1991.8.27

    authors: Sabato S,Agresta CA,Freeman GM,Salzman SK

    更新日期:1991-04-01 00:00:00

  • Metabolic levels in the corpus callosum and their structural and behavioral correlates after moderate to severe pediatric TBI.

    abstract::Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (ante...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2009.1058

    authors: Babikian T,Marion SD,Copeland S,Alger JR,O'Neill J,Cazalis F,Mink R,Giza CC,Vu JA,Hilleary SM,Kernan CL,Newman N,Asarnow RF

    更新日期:2010-03-01 00:00:00

  • Alpha-melanocyte stimulating hormone promotes regrowth of injured axons in the adult rat spinal cord.

    abstract::Peptides related to melanotropin (alphaMSH) and corticotropin (ACTH), collectively termed melanocortins, are known to improve the postlesion repair of injured peripheral nerves. In addition, melanocortins exert trophic effects on the outgrowth of neurites from central nervous system neurons in vitro. Here we report, f...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1999.16.543

    authors: Joosten EA,Majewska B,Houweling DA,Bär PR,Gispen WH

    更新日期:1999-06-01 00:00:00

  • Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat.

    abstract::The present study evaluated the effects of two novel N-methyl-D-aspartate (NMDA) receptor blockers and ifenprodil derivatives, CP-101,606 and CP-101,581, and their racemic mixture CP-98,113, on spatial memory and regional cerebral edema following experimental fluid-percussion (FP) brain injury in the rat (n = 66). Fif...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1997.14.211

    authors: Okiyama K,Smith DH,White WF,Richter K,McIntosh TK

    更新日期:1997-04-01 00:00:00

  • Profound differences in spontaneous long-term functional recovery after defined spinal tract lesions in the rat.

    abstract::The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or the complete dorsal...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2006.23.18

    authors: Hendriks WT,Eggers R,Ruitenberg MJ,Blits B,Hamers FP,Verhaagen J,Boer GJ

    更新日期:2006-01-01 00:00:00

  • Mild traumatic brain injury does not modify the cerebral blood flow profile of secondary forebrain ischemia in Wistar rats.

    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

    authors: Davis KL,Jenkins LW,DeWitt DS,Prough DS

    更新日期:1998-08-01 00:00:00

  • Neuroproteomics: a biochemical means to discriminate the extent and modality of brain injury.

    abstract::Diagnosis and treatment of stroke and traumatic brain injury remain significant health care challenges to society. Patient care stands to benefit from an improved understanding of the interactive biochemistry underlying neurotrauma pathobiology. In this study, we assessed the power of neuroproteomics to contrast bioch...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2010.1374

    authors: Ottens AK,Bustamante L,Golden EC,Yao C,Hayes RL,Wang KK,Tortella FC,Dave JR

    更新日期:2010-10-01 00:00:00

  • Voluntary muscle weakness and co-activation after chronic cervical spinal cord injury.

    abstract::Muscle strength was assessed from the maximum force that could be exerted voluntarily by triceps brachii muscles of 72 people with chronic cervical spinal cord injury (SCI) at or above C7, and 18 able-bodied (A-B) subjects. The magnitude of co-activation was estimated from the ratio of biceps brachii surface EMG to tr...

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.1998.15.149

    authors: Thomas CK,Tucker ME,Bigland-Ritchie B

    更新日期:1998-02-01 00:00:00

  • A Novel Method for Quantifying Human In Situ Whole Brain Deformation under Rotational Loading Using Sonomicrometry.

    abstract::Traumatic brain injuries (TBI) are one of the least understood injuries to the body. Finite element (FE) models of the brain have been crucial for understanding concussion and for developing injury mitigation systems; however, the experimental brain deformation data currently used to validate these models are limited....

    journal_title:Journal of neurotrauma

    pub_type: 杂志文章

    doi:10.1089/neu.2017.5362

    authors: Alshareef A,Giudice JS,Forman J,Salzar RS,Panzer MB

    更新日期:2018-03-01 00:00:00