Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice.


:Background and Purpose- The complexity and heterogeneity of stroke, as well as the associated comorbidities, may render neuroprotective drugs less efficacious in clinical practice. Therefore, the development of targeted therapies to specific patient subsets has become a high priority in translational stroke research. Ischemic stroke with type 2 diabetes mellitus has a nearly double mortality rate and worse neurological outcomes. In the present study, we tested our hypothesis that rFGF21 (recombinant human fibroblast growth factor 21) administration is beneficial for improving neurological outcomes of ischemic stroke with type 2 diabetes mellitus. Methods- Type 2 diabetes mellitus db/db and nondiabetic genetic control db/+ mice were subjected into permanent focal ischemia of distal middle cerebral artery occlusion, we examined the effects of poststroke administration with rFGF21 in systemic metabolic disorders, inflammatory gatekeeper PPARγ (peroxisome proliferator-activated receptor γ) activity at 3 days, mRNA expression of inflammatory cytokines and microglia/macrophage activation at 7 days in the perilesion cortex, and last neurological function deficits, ischemic brain infarction, and white matter integrity up to 14 days after stroke of db/db mice. Results- After permanent focal ischemia, diabetic db/db mice presented confounding pathological features, including metabolic dysregulation, more severe brain damage, and neurological impairment, especially aggravated proinflammatory response and white matter integrity loss. However, daily rFGF21 treatment initiated at 6 hours after stroke for 14 days significantly normalized systemic metabolic disorders, rescued PPARγ activity decline, inhibited proinflammatory cytokine mRNA expression, and M1-like microglia/macrophage activation in the brain. Importantly, rFGF21 also significantly reduced white matter integrity loss, ischemic brain infarction, and neurological function deficits up to 14 days after stroke. The potential mechanisms of rFGF21 may in part consist of potent systematic metabolic regulation and PPARγ-activation promotion-associated antiproinflammatory roles in the brain. Conclusions- Taken together, these results suggest rFGF21 might be a novel and potent candidate of the disease-modifying strategy for treating ischemic stroke with type 2 diabetes mellitus.






Jiang Y,Liu N,Wang Q,Yu Z,Lin L,Yuan J,Guo S,Ahn BJ,Wang XJ,Li X,Lo EH,Sun X,Wang X




Has Abstract


2018-12-01 00:00:00














  • Ejection fraction response of the left ventricle of the heart to acute cerebrovascular accident in patients with coronary artery disease.

    abstract::The ejection fraction (EF) of the left ventricle was measured by radionuclide ventriculography in 64 patients during an acute cerebrovascular accident. Sixteen patients (12 with coronary artery disease) died within two weeks of the onset of symptoms and had only one EF measurement. In the remaining 48 patients, the EF...


    pub_type: 杂志文章


    authors: Front D,Frankel A,Israel O,Aharon Y,Satinger A,Linn S

    更新日期:1986-07-01 00:00:00

  • Real-time validation of transcranial Doppler criteria in assessing recanalization during intra-arterial procedures for acute ischemic stroke: an international, multicenter study.

    abstract:BACKGROUND AND PURPOSE:We sought to evaluate the diagnostic accuracy of ultrasound criteria for recanalization during real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures in acute ischemic stroke patients in an international, multicenter study. METHODS:Consecutive acute ischemic stroke pa...


    pub_type: 杂志文章,多中心研究


    authors: Tsivgoulis G,Ribo M,Rubiera M,Vasdekis SN,Barlinn K,Athanasiadis D,Bavarsad Shahripour R,Giannopoulos S,Stamboulis E,Harrigan MR,Molina CA,Alexandrov AV

    更新日期:2013-02-01 00:00:00

  • Experimental regional cerebral ischemia in the middle cerebral artery territory in primates. Part 3: effects on brain water and electrolytes in the late phase of acute MCA stroke.

    abstract::Experimental regional cerebral ischemia was produced in the middle cerebral artery (MCA) territory in primates (M. mulatta) by macrosphere embolization. Determinations of percentage tissue dry weight and tissue sodium and potassium concentrations were obtained in samples from the ischemic and non-ischemic hemispheres ...


    pub_type: 杂志文章


    authors: Bremer AM,Yamada K,West CR

    更新日期:1978-07-01 00:00:00

  • Pharmacologic interventions for stroke: looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch.

    abstract:BACKGROUND AND PURPOSE:The majority of pharmacological agents for stroke were developed based on the assumption that neurological deficits will be reduced upon the successful interruption of biochemical mechanisms leading to neuronal death. Despite significant evidence of preclinical efficacy, none of these agents succ...


    pub_type: 杂志文章,评审


    authors: Chavez JC,Hurko O,Barone FC,Feuerstein GZ

    更新日期:2009-10-01 00:00:00

  • Endovascular Treatment for Acute Ischemic Stroke in Patients on Oral Anticoagulants: Results From the MR CLEAN Registry.

    abstract::Background and Purpose- The use of oral anticoagulants (OAC) is considered a contra-indication for intravenous thrombolytics as acute treatment of ischemic stroke. However, little is known about the risks and benefits of endovascular treatment in patients on prior OAC. We aim to compare outcomes after endovascular tre...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Goldhoorn RB,van de Graaf RA,van Rees JM,Lingsma HF,Dippel DWJ,Hinsenveld WH,Postma A,van den Wijngaard I,van Zwam WH,van Oostenbrugge RJ,Roozenbeek B,MR CLEAN Registry Investigators—Group Authors.

    更新日期:2020-06-01 00:00:00

  • Third European Stroke Science Workshop.

    abstract::Lake Eibsee, Garmisch-Partenkirchen, November 19 to 21, 2015: The European Stroke Organization convened >120 stroke experts from 27 countries to discuss latest results and hot topics in clinical, translational, and basic stroke research. Since its inception in 2011, the European Stroke Science Workshop has become a co...


    pub_type: 杂志文章


    authors: Dichgans M,Planas AM,Biessels GJ,van der Worp B,Sudlow C,Norrving B,Lees K,Mattle HP

    更新日期:2016-07-01 00:00:00

  • Homozygous ALDH2*2 Is an Independent Risk Factor for Ischemic Stroke in Taiwanese Men.

    abstract:BACKGROUND AND PURPOSE:The *2 allele of the aldehyde dehydrogenase 2 gene (ALDH2) is the most common variant in Asian populations. The variant resulting in enzyme dysfunction was highly related to coronary artery disease. Recently, genome-wide association studies also discovered that the 12q24 locus near ALDH2 gene was...


    pub_type: 杂志文章


    authors: Sung YF,Lu CC,Lee JT,Hung YJ,Hu CJ,Jeng JS,Chiou HY,Peng GS

    更新日期:2016-09-01 00:00:00

  • Age Threshold for Ischemic Stroke Risk in Atrial Fibrillation.

    abstract::Background and Purpose- Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), the appropriate age threshold (eg, CHA2DS2-VASc score [congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vas...


    pub_type: 杂志文章


    authors: Kim TH,Yang PS,Yu HT,Jang E,Uhm JS,Kim JY,Pak HN,Lee MH,Joung B,Lip GYH

    更新日期:2018-08-01 00:00:00

  • Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV Autopsy Cohort.

    abstract:BACKGROUND AND PURPOSE:Autopsy series of patients with AIDS have found a 4% to 29% prevalence of cerebral infarction. Little is known of the prevalence of cerebral infarction when not associated with non-HIV central nervous system (CNS) infection, lymphoma, or cardioembolic sources. Clinical correlation has seldom been...


    pub_type: 杂志文章


    authors: Connor MD,Lammie GA,Bell JE,Warlow CP,Simmonds P,Brettle RD

    更新日期:2000-09-01 00:00:00

  • Tissue-Selective Salvage of the White Matter by Successful Endovascular Stroke Therapy.

    abstract:BACKGROUND AND PURPOSE:White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determ...


    pub_type: 杂志文章


    authors: Kleine JF,Kaesmacher M,Wiestler B,Kaesmacher J

    更新日期:2017-10-01 00:00:00

  • Effect of BQ-123 and tissue plasminogen activator on vasospasm after subarachnoid hemorrhage in monkeys.

    abstract:BACKGROUND AND PURPOSE:We aimed to determine the effect of intracisternal administration of an endothelin-A receptor antagonist (BQ-123) against vasospasm in a monkey model and to determine whether this drug would have adverse interactions with intracisternal tissue plasminogen activator (TPA). METHODS:Thirty-three mo...


    pub_type: 杂志文章


    authors: Kim CJ,Bassiouny M,Macdonald RL,Weir B,Johns LM

    更新日期:1996-09-01 00:00:00

  • Effect of atherosclerosis on cerebral vascular responses to activation of leukocytes and platelets in monkeys.

    abstract::The goal of this study was to test the hypothesis that atherosclerosis alters responses of cerebral arteries and the ocular circulation to the activation in vivo of leukocytes and platelets. We measured blood flow to the brain and eye using microspheres and pressure in the cerebral microvessels of normal and atheroscl...


    pub_type: 杂志文章


    authors: Faraci FM,Lopez AG,Breese K,Armstrong ML,Heistad DD

    更新日期:1991-06-01 00:00:00

  • Does Contralesional Hand Function After Neonatal Stroke Only Depend on Lesion Characteristics?

    abstract:BACKGROUND AND PURPOSE:In children having suffered from neonatal arterial ischemic stroke, the relationship between contralesional hand performance and structural changes in brain areas remote from the infarct site was examined. METHODS:Using voxel-based morphometry, we correlated contralesional gross manual dexterity...


    pub_type: 杂志文章


    authors: Dinomais M,Hertz-Pannier L,Groeschel S,Delion M,Husson B,Kossorotoff M,Renaud C,Chabrier S,The Tich SN,AVCnn Study Group.

    更新日期:2016-06-01 00:00:00

  • Cerebral blood flow immediately following brief circulatory stasis.

    abstract::Cerebral blood flow was studied in rabbits immediately following complete circulatory stasis of varying duration. Systemic arterial pressure was measured continuously. The postischemic circulation was examined both by an infusion of carbon black and, in separate experiments, by injection of 14C-antipyrine into the blo...


    pub_type: 杂志文章


    authors: Fischer EG,Ames A 3rd,Lorenzo AV

    更新日期:1979-07-01 00:00:00

  • Impaired endothelial function of forearm resistance arteries in CADASIL patients.

    abstract:BACKGROUND AND PURPOSE:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy, which mainly involves the brain causing stroke and dementia. Mice expressing the mutated protein display early dysfunction in vasoreactivity in resistance arteries, b...


    pub_type: 杂志文章


    authors: Stenborg A,Kalimo H,Viitanen M,Terent A,Lind L

    更新日期:2007-10-01 00:00:00

  • Endogenous platelet activating factor does not modulate blood flow and metabolism in normal rat brain.

    abstract::Both platelet activating factor and eicosanoids participate in the cerebrovascular response to ischemia. Eicosanoids also modulate cerebrovascular tone under normal physiologic circumstances, but a similar role for platelet activating factor has not been investigated. Therefore, using 16 rats, we studied the effects o...


    pub_type: 杂志文章


    authors: Kochanek PM,Melick JA,Schoettle RJ,Magargee MJ,Evans RW,Nemoto EM

    更新日期:1990-03-01 00:00:00

  • Mechanisms and timing of deaths from cerebral infarction.

    abstract::Clinicopathologic correlations were reviewed in 100 cases of recent cerebral infarctions in the internal carotid artery distribution. The most frequent cause of death was transtentorial herniation, followed in frequency by pneumonia, cardiac causes, and pulmonary embolism. Thirty-six percent of all patients and 47% of...


    pub_type: 杂志文章


    authors: Bounds JV,Wiebers DO,Whisnant JP,Okazaki H

    更新日期:1981-07-01 00:00:00

  • Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol.

    abstract::Functional assessment of animals following experimental cerebral ischemia is often difficult due to the passive nature of many neurologic exams. We attempted to increase the objectivity of motor function evaluation by adapting quantifiable behavioral tests and actively testing rats' motor capability following a cerebr...


    pub_type: 杂志文章


    authors: Combs DJ,D'Alecy LG

    更新日期:1987-03-01 00:00:00

  • Cerebral thromboembolism among young women and men in Denmark 1977-1982.

    abstract::In the period 1977-1982, the Danish National Patient Register recorded 1000 cases of cerebral thromboembolic attacks among women 15-44 years of age, and 971 cases among men of the same age. Cerebral infarction accounted for 70% of cases and transient ischemic attacks (TIA) for the remaining 30%. By analysing this mate...


    pub_type: 杂志文章


    authors: Lidegaard O,Soe M,Andersen MV

    更新日期:1986-07-01 00:00:00

  • Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage: Randomized Controlled Trial.

    abstract:BACKGROUND AND PURPOSE:Delayed cerebral ischemia (DCI) is the most important cause for a poor clinical outcome after a subarachnoid hemorrhage. The aim of this study was to assess whether goal-directed hemodynamic therapy (GDHT), as compared to standard clinical care, reduces the rate of DCI after subarachnoid hemorrha...


    pub_type: 杂志文章,随机对照试验


    authors: Anetsberger A,Gempt J,Blobner M,Ringel F,Bogdanski R,Heim M,Schneider G,Meyer B,Schmid S,Ryang YM,Wostrack M,Schneider J,Martin J,Ehrhardt M,Jungwirth B

    更新日期:2020-08-01 00:00:00

  • Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation.

    abstract:BACKGROUND AND PURPOSE:Mild hypothermia is possibly the single most effective method of cerebroprotection developed to date. However, many questions regarding mild hypothermia remain to be addressed before its potential implementation in the treatment of human stroke. Here we report the results of 2 studies designed to...


    pub_type: 杂志文章


    authors: Maier CM,Ahern Kv,Cheng ML,Lee JE,Yenari MA,Steinberg GK

    更新日期:1998-10-01 00:00:00

  • Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats.

    abstract:BACKGROUND AND PURPOSE:Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated ...


    pub_type: 杂志文章


    authors: Aoki T,Kataoka H,Morimoto M,Nozaki K,Hashimoto N

    更新日期:2007-01-01 00:00:00

  • Anxiety and the Risk of Stroke: The Rotterdam Study.

    abstract:BACKGROUND AND PURPOSE:It is unclear whether anxiety is a risk factor for stroke. We assessed the association between anxiety and the risk of incident stroke. METHODS:This population-based cohort study was based on 2 rounds of the Rotterdam Study. Each round was taken separately as baseline. In 1993 to 1995, anxiety s...


    pub_type: 杂志文章


    authors: Portegies ML,Bos MJ,Koudstaal PJ,Hofman A,Tiemeier HW,Ikram MA

    更新日期:2016-04-01 00:00:00

  • Ultrasonic demonstration of external and internal carotid patency with common carotid occlusion: a preliminary report.

    abstract::Non-invasive ultrasonic imaging of the carotid bifurcation by duplex scanning and ultrasonic arteriography combined with pulsed Doppler spectrum analysis demonstrated patency of the external and internal carotid arteries distal to a common carotid occlusion in 3 patients. Common carotid occlusion is not invariably ass...


    pub_type: 杂志文章


    authors: Blackshear WM Jr,Phillips DJ,Bodily KC,Strandness DE Jr

    更新日期:1980-05-01 00:00:00

  • A systematic review of the risks of stroke and death due to endarterectomy for symptomatic carotid stenosis.

    abstract:BACKGROUND AND PURPOSE:Carotid endarterectomy reduces the risk of carotid territory ischemic stroke ipsilateral to a recently symptomatic severe carotid stenosis. However, the benefit is limited by the risks of stroke and death associated with the operation. Although reported surgical risks vary enormously, there has b...


    pub_type: 杂志文章,评审


    authors: Rothwell PM,Slattery J,Warlow CP

    更新日期:1996-02-01 00:00:00

  • Effects of global cerebral ischemia in the pregnant rat.

    abstract:BACKGROUND AND PURPOSE:Stroke during pregnancy is an emerging concern. Although females undergo many physiological, endocrine, and neurological alterations during pregnancy, the consequences of such changes on outcome after stroke are unclear. It is predicted that increases in steroid hormones observed during pregnancy...


    pub_type: 杂志文章


    authors: Spencer SJ,Galic MA,Tsutsui M,Pittman QJ,Mouihate A

    更新日期:2008-03-01 00:00:00

  • Functional and motor outcome 5 years after stroke is equivalent to outcome at 2 months: follow-up of the collaborative evaluation of rehabilitation in stroke across Europe.

    abstract:BACKGROUND AND PURPOSE:Recovery of patients within the first 6 months after stroke is well documented, but there has been little research on long-term recovery. The aim of this study was to analyze functional and motor recovery between admission to rehabilitation centres and 5 years after stroke. METHODS:This follow-u...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Meyer S,Verheyden G,Brinkmann N,Dejaeger E,De Weerdt W,Feys H,Gantenbein AR,Jenni W,Laenen A,Lincoln N,Putman K,Schuback B,Schupp W,Thijs V,De Wit L

    更新日期:2015-06-01 00:00:00

  • Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.

    abstract:BACKGROUND AND PURPOSE:White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when pro...


    pub_type: 杂志文章


    authors: van Leijsen EMC,Bergkamp MI,van Uden IWM,Ghafoorian M,van der Holst HM,Norris DG,Platel B,Tuladhar AM,de Leeuw FE

    更新日期:2018-06-01 00:00:00

  • The effect of a stroke unit: reductions in mortality, discharge rate to nursing home, length of hospital stay, and cost. A community-based study.

    abstract:BACKGROUND AND PURPOSE:Treatment of stroke patients in specialized stroke units has become more frequent, yet the effect of this treatment has not been determined. METHODS:In a community-based, prospective, and consecutive study of 1241 unselected acute stroke patients, we compared outcome of stroke treatment between ...


    pub_type: 杂志文章


    authors: Jørgensen HS,Nakayama H,Raaschou HO,Larsen K,Hübbe P,Olsen TS

    更新日期:1995-07-01 00:00:00

  • Outcome in patients with acute basilar artery occlusion requiring mechanical ventilation.

    abstract:BACKGROUND AND PURPOSE:Many patients with acute basilar artery occlusion may require endotracheal intubation and mechanical ventilation. The circumstances and predictive value for outcome in these patients are not well documented. METHODS:We reviewed the medical records of 25 patients admitted into the intensive care ...


    pub_type: 杂志文章


    authors: Wijdicks EF,Scott JP

    更新日期:1996-08-01 00:00:00