FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke.

Abstract:

:CD8+ T cells are recognized as key players in exacerbation of ischemic stroke; however, the underlying mechanism in modulating the function of CD8+ T cells has not been completely elucidated. Here, we uncovered that FasL enhanced the cytotoxicity of CD8+ T cells to neurons after ischemic stroke. Inactivation of FasL specific on CD8+ T cells protected against brain damage and neuron loss. Proteomic analysis identified that PDPK1 functioned downstream of FasL signaling and inhibition of PDPK1 effectively reduced cytotoxicity of CD8+ T cells and improved ischemic neurological deficits. Taken together, these results highlight an intrinsic FasL-PDPK1 pathway regulating the cytotoxicity of CD8+ T cells in ischemic stroke.

journal_name

Transl Stroke Res

authors

Fan L,Zhang CJ,Zhu L,Chen J,Zhang Z,Liu P,Cao X,Meng H,Xu Y

doi

10.1007/s12975-019-00749-0

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

747-761

issue

4

eissn

1868-4483

issn

1868-601X

pii

10.1007/s12975-019-00749-0

journal_volume

11

pub_type

杂志文章
  • Tissue plasminogen activator induced delayed edema in experimental porcine intracranial hemorrhage: reduction with plasminogen activator inhibitor-1 administration.

    abstract::Hematoma puncture and subsequent clot lysis with recombinant tissue plasminogen activator (rtPA) emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH) and is associated with delayed edema possibly counteracting the beneficial effects of hematoma volume reduction. We hypothesized that immedia...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-012-0188-3

    authors: Keric N,Maier GS,Samadani U,Kallenberg K,Dechent P,Brueck W,Heuer J,Rohde V

    更新日期:2012-07-01 00:00:00

  • Biomarkers Related to Carotid Intima-Media Thickness and Plaques in Long-Term Survivors of Ischemic Stroke.

    abstract::Lifestyle risk factors, inflammation and genetics play a role in the development of atherosclerosis. We therefore studied Fc gamma receptor (FcγR) polymorphisms, interleukin (IL)-10 polymorphisms and other biomarkers related to carotid intima-media thickness (cIMT) in patients with ischemic stroke at a young age. Pati...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-015-0403-0

    authors: Waje-Andreassen U,Naess H,Thomassen L,Maroy TH,Mazengia KY,Eide GE,Vedeler CA

    更新日期:2015-08-01 00:00:00

  • Shifts in Leukocyte Counts Drive the Differential Expression of Transcriptional Stroke Biomarkers in Whole Blood.

    abstract::Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-018-0623-1

    authors: O'Connell GC,Treadway MB,Tennant CS,Lucke-Wold N,Chantler PD,Barr TL

    更新日期:2019-02-01 00:00:00

  • Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage.

    abstract::Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement ex...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-019-00757-0

    authors: van Dijk BJ,Meijers JCM,Kloek AT,Knaup VL,Rinkel GJE,Morgan BP,van der Kamp MJ,Osuka K,Aronica E,Ruigrok YM,van de Beek D,Brouwer M,Pekna M,Hol EM,Vergouwen MDI

    更新日期:2020-08-01 00:00:00

  • Neuroimaging of stroke and ischemia in animal models.

    abstract::Magnetic resonance imaging (MRI) has dramatically changed our ability to diagnose and treat stroke as well as follow its evolution and response to treatment. Early stroke and ischemia can be visualized using diffusion-weighted imaging that utilizes water diffusion within tissues as a reporter for evolving neuropatholo...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0139-4

    authors: Obenaus A,Ashwal S

    更新日期:2012-03-01 00:00:00

  • Experimental subarachnoid hemorrhage: double cisterna magna injection rat model--assessment of delayed pathological effects of cerebral vasospasm.

    abstract::Aneurysmal subarachnoid hemorrhage comprises of an early phase after the bleeding and a late phase of delayed consequences of the bleeding. The development of delayed injury mechanisms, like the reduction of cerebral blood flow (CBF) due to cerebral vasospasm (CVS), seems mainly to depend on the amount and the duratio...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-015-0392-z

    authors: Güresir E,Schuss P,Borger V,Vatter H

    更新日期:2015-06-01 00:00:00

  • Beneficial Effects of Delayed P7C3-A20 Treatment After Transient MCAO in Rats.

    abstract::Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0565-z

    authors: Loris ZB,Hynton JR,Pieper AA,Dietrich WD

    更新日期:2018-04-01 00:00:00

  • Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit.

    abstract::Increasingly, experimental research in subarachnoid hemorrhage (SAH) has investigated early brain injury and the microcirculation. A number of pathophysiological changes occur in the cerebral microvessels after SAH including altered vasoreactivity, vasoconstriction, inflammation, blood-brain barrier impairment, increa...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-014-0323-4

    authors: Tso MK,Macdonald RL

    更新日期:2014-04-01 00:00:00

  • Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia.

    abstract::Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury i...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-016-0509-z

    authors: Yigitkanli K,Zheng Y,Pekcec A,Lo EH,van Leyen K

    更新日期:2017-04-01 00:00:00

  • Translational strategies for neuroprotection in ischemic stroke--focusing on acid-sensing ion channel 1a.

    abstract::Ischemic stroke contributes to the majority of brain injuries and remains to be a leading cause of death and long-term disability. Despite the devastating pathology and high incidence of disease, there remain only few treatment options (TPA and endovascular procedures), which may be hampered by time-dependent administ...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-013-0319-5

    authors: O'Bryant Z,Vann KT,Xiong ZG

    更新日期:2014-02-01 00:00:00

  • Healthcare Economics of Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage in the United States.

    abstract::Hydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition's high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health syste...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-019-00697-9

    authors: Adil SM,Liu B,Charalambous LT,Kiyani M,Gramer R,Swisher CB,Verbick LZ,McCabe A,Parente BA,Pagadala P,Lad SP

    更新日期:2019-12-01 00:00:00

  • Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage.

    abstract::Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-018-0647-6

    authors: Neulen A,Meyer S,Kramer A,Pantel T,Kosterhon M,Kunzelmann S,Goetz H,Thal SC

    更新日期:2018-07-12 00:00:00

  • Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

    abstract::Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular disease...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0585-8

    authors: Conzen C,Albanna W,Weiss M,Kürten D,Vilser W,Kotliar K,Zäske C,Clusmann H,Schubert GA

    更新日期:2018-06-01 00:00:00

  • Neurovascular injury in acute hyperglycemia and diabetes: A comparative analysis in experimental stroke.

    abstract:BACKGROUND:Admission hyperglycemia impacts ischemic stroke deleteriously but the relative role of acute hyperglycemia (HG) versus diabetes in the pathogenesis of this poor outcome is not clear. PURPOSE:To determine the effect of acute HG on neurovascular outcomes of stroke under control and diabetic conditions. METHO...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0083-3

    authors: Elgebaly MM,Ogbi S,Li W,Mezzetti EM,Prakash R,Johnson MH,Bruno A,Fagan SC,Ergul A

    更新日期:2011-09-01 00:00:00

  • Correction to: Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion.

    abstract::There was an error in Fig. 2d. The correct Fig. 2d is shown below. ...

    journal_title:Translational stroke research

    pub_type: 已发布勘误

    doi:10.1007/s12975-020-00871-4

    authors: Yoshimura S,Uchida K,Sakai N,Imamura H,Yamagami H,Tanaka K,Ezura M,Nonaka T,Matsumoto Y,Shibata M,Ohta H,Morimoto M,Fukawa N,Hatano T,Enomoto Y,Takeuchi M,Ota T,Shimizu F,Kimura N,Kamiya Y,Shimamura N,Morimoto T

    更新日期:2020-10-22 00:00:00

  • Positron Emission Tomography After Ischemic Brain Injury: Current Challenges and Future Developments.

    abstract::Positron emission tomography (PET) is widely used in clinical and animal studies, along with the development of diverse tracers. The biochemical characteristics of PET tracers may help uncover the pathophysiological consequences of cardiac arrest (CA) and ischemic stroke, which include cerebral ischemia and reperfusio...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-019-00765-0

    authors: Wang Z,Mascarenhas C,Jia X

    更新日期:2020-08-01 00:00:00

  • Biological sex and mechanisms of ischemic brain injury.

    abstract::Cerebrovascular disease is a leading cause of death-from-disease and of disability worldwide, affecting some 15 million people. The incidence of stroke or "brain attack" is unlikely to recede for a decade at minimum by most predictions, despite large public health initiatives in stroke prevention. It has been well est...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-012-0238-x

    authors: Herson PS,Palmateer J,Hurn PD

    更新日期:2013-08-01 00:00:00

  • Distal occlusion of the middle cerebral artery in mice: are we ready to assess long-term functional outcome?

    abstract::Rodent animal models of stroke are widely used with brain ischemia inducible by various occlusion methods. Permanent or transient occlusion of the distal portion of the middle cerebral artery (MCAO) offers a reproducible model with low mortality rates, and it is the most likely model of choice for mid- and long-term s...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-012-0234-1

    authors: Rosell A,Agin V,Rahman M,Morancho A,Ali C,Koistinaho J,Wang X,Vivien D,Schwaninger M,Montaner J

    更新日期:2013-06-01 00:00:00

  • Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO.

    abstract::An argument for preclinical stroke research to make more use of the permanent middle cerebral artery occlusion (MCAO) model, rather than transient MCAO, is presented. Despite STAIR recommending permanent MCAO as the primary model, preclinical stroke research has not been listened. In 2012, Hossmann reported that 64% o...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0554-2

    authors: McBride DW,Zhang JH

    更新日期:2017-07-17 00:00:00

  • A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease.

    abstract::Cavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1, CCM2, and CCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to e...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-019-00725-8

    authors: McKerracher L,Shenkar R,Abbinanti M,Cao Y,Peiper A,Liao JK,Lightle R,Moore T,Hobson N,Gallione C,Ruschel J,Koskimäki J,Girard R,Rosen K,Marchuk DA,Awad IA

    更新日期:2020-06-01 00:00:00

  • Intracerebral hemorrhage: clinical overview and pathophysiologic concepts.

    abstract::Intracerebral hemorrhage is by far the most destructive form of stroke. Apart from the management in a specialized stroke or neurological intensive care unit (NICU), no specific therapies have been shown to consistently improve outcomes after ICH. Current guidelines endorse early aggressive optimization of physiologic...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-012-0175-8

    authors: Rincon F,Mayer SA

    更新日期:2012-07-01 00:00:00

  • Tumor necrosis factor-α modulates cerebral aneurysm formation and rupture.

    abstract::Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-013-0287-9

    authors: Starke RM,Raper DM,Ding D,Chalouhi N,Owens GK,Hasan DM,Medel R,Dumont AS

    更新日期:2014-04-01 00:00:00

  • Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage.

    abstract::Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for ...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-020-00796-y

    authors: van Lieshout JH,Marbacher S,Muhammad S,Boogaarts HD,Bartels RHMA,Dibué M,Steiger HJ,Hänggi D,Kamp MA

    更新日期:2020-10-01 00:00:00

  • Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Diabetic Rats via Enhanced Post-Ischemic Mitochondrial Dysfunction.

    abstract::Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-018-0622-2

    authors: Shukla V,Fuchs P,Liu A,Cohan CH,Dong C,Wright CB,Perez-Pinzon MA,Dave KR

    更新日期:2019-02-01 00:00:00

  • Validity of bone marrow stromal cell expansion by animal serum-free medium for cell transplantation therapy of cerebral infarct in rats-a serial MRI study.

    abstract::This study was aimed to test the hypothesis that human bone marrow stromal cells (hBMSC) expanded in fetal calf serum (FCS)-free, platelet lysate (PL)-containing medium would retain their capacity of migration, survival, and neural differentiation when transplanted into the infarct brain, using serial in vivo magnetic...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0098-9

    authors: Ito M,Kuroda S,Sugiyama T,Shichinohe H,Takeda Y,Nishio M,Koike T,Houkin K

    更新日期:2011-09-01 00:00:00

  • Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

    abstract::Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related gene...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0577-8

    authors: Kinouchi T,Kitazato KT,Shimada K,Yagi K,Tada Y,Matsushita N,Kurashiki Y,Satomi J,Sata M,Nagahiro S

    更新日期:2018-06-01 00:00:00

  • Role of Exosomes as a Treatment and Potential Biomarker for Stroke.

    abstract::Approximately, 16 million strokes occur worldwide each year, causing 6 million deaths and considerable disability, implying an enormous social, individual health, and economic burden. Due to this high incidence, strategies to promote stroke recovery are urgently needed. Research into new therapeutic approaches for str...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-018-0654-7

    authors: Otero-Ortega L,Laso-García F,Gómez-de Frutos M,Fuentes B,Diekhorst L,Díez-Tejedor E,Gutiérrez-Fernández M

    更新日期:2019-06-01 00:00:00

  • Velocity Curvature Index: a Novel Diagnostic Biomarker for Large Vessel Occlusion.

    abstract::Despite being a conveniently portable technology for stroke assessment, Transcranial Doppler ultrasound (TCD) remains widely underutilized due to complex training requirements necessary to reliably obtain and interpret cerebral blood flow velocity (CBFV) waveforms. The validation of objective TCD metrics for large ves...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-018-0667-2

    authors: Thorpe SG,Thibeault CM,Wilk SJ,O'Brien M,Canac N,Ranjbaran M,Devlin C,Devlin T,Hamilton RB

    更新日期:2019-10-01 00:00:00

  • Author Correction: Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.

    abstract::In the original publication of the article, there was a switched order of author names. ...

    journal_title:Translational stroke research

    pub_type: 杂志文章,已发布勘误

    doi:10.1007/s12975-018-0618-y

    authors: Dorňák T,Král M,Sedláčková Z,Šaňák D,Čecháková E,Divišová P,Zapletalová J,Kaňovský P

    更新日期:2018-12-01 00:00:00

  • An Endovascular Perforation Model of Subarachnoid Haemorrhage in Rat Produces Heterogeneous Infarcts that Increase with Blood Load.

    abstract::Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on society. Despite this, pharmacological treatment options are limited. Appropriate animal modelling of SAH is essential for the development of neuroprotective drugs, but experimental SAH often fails to produce widespread neuronal loss, as fre...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0124-y

    authors: Greenhalgh AD,Rothwell NJ,Allan SM

    更新日期:2012-03-01 00:00:00