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Sample records for ischemic myocardiopathy trasplante

  1. Clinical effects of carvedilol and trimetazidine for the treatmentof alcoholic myocardiopathy

    PubMed Central

    Li, Hui; Liu, Fu-Yuan; Li, Xiao-Lan; Li, Xiao-Mei; Zhu, Lei

    2016-01-01

    The aim of the study was to compare the clinical effects of carvedilol and trimetazidine for the treatment of alcoholic cardiomyopathy. A total of 60 patients diagnosed with alcoholic cardiomyopathy were enrolled in the study. The patients were randomly divided into the carvedilol (n=20), trimetazidine (n=20) and control (n=20) groups. The patients in the control, carvedilol and trimetazidine groups were treated with conventional drugs, conventional drugs + carvedil and conventional drugs + trimetazidine respectively, for 12 weeks. The patients were compared for their heart functions [left ventricular ejection fraction (LVEF), C-reactive protein (CRP) and 6 min walking], heart rate, blood pressure and heart enlargement (cardiothoracic proportion and left ventricular diameter) before and after treatment. The parameters studied for heart functions, heart rate, blood pressure, heart enlargement, clinical effects before and after treatment were statistically insignificant (p>0.05). After treatment, the carvedilol and trimetazidine groups showed higher LVEF and CRP, longer walking distance in 6 min, as well as lower heart rate and blood pressure (both systolic and diastolic) compared to the control group. Similarly, the cardiothoracic proportion and left ventricular internal diameter for the carvedilol and trimetazidine groups was lower than those of the control group, with better clinical effects (p<0.05). In conclusion, the curative effects of the carvedilol and trimetazidine groups of alcoholic myocardiopathy similar. Both are safe agents that may improve the cardiac function and heart expansion of patients. PMID:27446307

  2. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  3. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  4. Ischemic preconditioning protects against ischemic brain injury.

    PubMed

    Ma, Xiao-Meng; Liu, Mei; Liu, Ying-Ying; Ma, Li-Li; Jiang, Ying; Chen, Xiao-Hong

    2016-05-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  5. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  6. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Jul 12,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  7. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

  8. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  9. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  10. [Effect of liver trasplantation on familial amyloidotic polyneuropathy (FAP) and its limt].

    PubMed

    Ando, Yukio

    2011-11-01

    Familial amyloidotic polyneuropathy (FAP) is a hereditary intractable disease induced by mutated transthyretin (TTR). Since TTR is predominantly synthesized by liver, liver transplantation has been performed to halt the clinical symptoms of FAP in the worldwide. It has been well documented that liver transplantation could halt the progression of FAP manifestations. However, the surgery could not prevent ocular symptoms and in some cases, cardiopathy and neuroparthy progressed even after liver trasplantation. Quantitative analyses for changes in the amount of amyloid deposition and ratio of wild type and variant type of TTR for autopsy transplanted FAP cases revealed that the amount of amyloid deposition decreased in most of the organs, but in heart and lung, the amount increased even after liver transplantation. In those organs, the ratio of wild type to variant TTR increased. Since liver transplantation has several problems, we are now performing several new therapeutic researches for FAP, such as development of drug stabilizing tetrameric form of TTR, siRNA therapy to stop TTR production, and low molecular compounds for preventing misfolding of TTR. PMID:22277510

  11. Adenosine and Ischemic Preconditioning

    PubMed Central

    Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

    2012-01-01

    Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

  12. Ischemic tissue injury.

    PubMed Central

    Jennings, R. B.; Ganote, C. E.; Reimer, K. A.

    1975-01-01

    The subendocardial to subepicardial gradient in the severity of ischemia following acute coronary occlusion is described. The effects of mild, moderate, and severe ischemia on cell structure and function are compared in summary form, and special attention is given to the effects of severe ischemia on myocardial cells. The characteristics of reversible and irreversible ischemic injury are defined in biologic terms. The failure of cell volume regulation in cells which have entered an irreversible state of ischemic injury is demonstrated by the use of free-hand slices in vitro. Irreversibility is associated with structural defects in the plasma membrane and is reflected in an increased slice inulin-diffusible space, increased slice H2O and Na+ content, and failure of the tissue to maintain the high K+ and Mg2+ levels characteristic of normal left ventricular myocardium. Defective cell membrane function is an early feature of irreversible ischemic injury and may be a primary event in the genesis of the irreversible state. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1180331

  13. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  14. Acute Ischemic Stroke Intervention.

    PubMed

    Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L

    2016-06-01

    Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835

  15. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  16. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke. PMID:23805635

  17. Ischemic ulcers - self-care

    MedlinePlus

    ... restrict blood flow. Certain lifestyle changes can help prevent ischemic ulcers. If you have a wound, taking these steps can improve blood flow and aid healing. Quit smoking. Smoking can lead to clogged arteries. ...

  18. Ischemic Stroke after Heart Transplantation.

    PubMed

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-05-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  19. Ischemic Stroke after Heart Transplantation

    PubMed Central

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-01-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  20. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  1. [Phenomenon of heart ischemic postconditioning].

    PubMed

    Maslov, L N; Mrochek, A G; Hanus, L; Pei, J -M; Zhang, Y; Wang, H; Naryzhnaia, N V

    2012-08-01

    Authors of review analyzed papers on problem of heart ischemic postconditioning. In the review, it was demonstrated that postconditioning decreased an infarct size, prevented cardiomyocytes apoptosis, improved cardiac contractility in reperfusion period, augmented cardiac tolerance to arrhythmogenic impact ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress in myocardium. PMID:23155619

  2. Microglia in ischemic brain injury

    PubMed Central

    Weinstein, Jonathan R; Koerner, Ines P; Möller, Thomas

    2010-01-01

    Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity. PMID:20401171

  3. Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness.

    PubMed

    Pan, Jingrui; Li, Xiangpen; Peng, Ying

    2016-07-01

    Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future. PMID:26812782

  4. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  5. [Ischemic cerebrovascular accidents in childhood].

    PubMed

    Pascual Pascual, S I; Pascual Castroviejo, I; Vélez, A

    1988-04-01

    Authors review 53 children, aged 0 to 14 years, affected with cerebrovascular ischemic strokes. Largest aetiological groups were: a) congenital heart disease, 16 patients; b) arteritis of unknown cause, 11; c) idiopathic arterial occlusion without arteritis images on angiography, 7; d) moyamoya disease, 6; and d) local or systemic infections, 5. The mode of onset was as completed stroke in 72% and stroke in evolution in 24%. After acute stage 17.6% of patients presented other definitive strokes, 11.7% suffered only transient ischemic strokes (TIA), and 4% reversible ischemic neurologic deficits (RIND). Mean follow-up was 4.36 years, 9.8% of patients died, 11.8% recovered completely and 52.9% improved after initial stroke. Poor global evolution was associated with heart disease (p less than 0.05) and with onset of strokes before age 2 (p less than 0.05). Most important sequelae, besides motor impairment, were epilepsy (49%) and mental retardation (50% got less than IQ 80). Late epilepsy was associated with seizures at onset (p less than 0.05). Clinical factors of adverse mental development were: a) seizures at onset, b) late epilepsy and c) stroke before age 2. 66% of cases had two or more arterial lesions in the same or in different arterial trees. Therefore, embolic and arteritic factors probably play an important role in infancy and childhood stroke. PMID:3400936

  6. Intravenous thrombolytics for ischemic stroke.

    PubMed

    Barreto, Andrew D

    2011-07-01

    For many decades, intravenous (IV) thrombolytics have been delivered to treat acute thrombosis. Although these medications were originally effective for coronary thrombosis, their mechanisms have proven beneficial for many other disease processes, including ischemic stroke. Treatment paradigms for acute ischemic stroke have largely followed those of cardiology. Specifically, the aim has been to recanalize the occluded artery and to restore perfusion to the brain that remains salvageable. To that end, rapid clot lysis was sought using thrombolytic medicines already proven effective in the coronary arteries. IV-thrombolysis for ischemic stroke began its widespread adoption in the late 1990s after the publication of the National Institute of Neurological Disorders and Stroke study. Since that time, other promising IV-thrombolytics have been developed and tested in human trials, but as of yet, none have been proven better than a placebo. Adjunctive treatments are also being evaluated. The challenge remains balancing reperfusion and salvaging brain tissue with the potential risks of brain hemorrhage. PMID:21638138

  7. Management of ischemic optic neuropathies

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

  8. Peroxisomal Biogenesis in Ischemic Brain

    PubMed Central

    Young, Jennifer M.; Nelson, Jonathan W.; Cheng, Jian; Zhang, Wenri; Mader, Sarah; Davis, Catherine M.; Morrison, Richard S.

    2015-01-01

    Abstract Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109–120. PMID:25226217

  9. Symptoms of transient ischemic attack.

    PubMed

    Kim, Jong S

    2014-01-01

    Transient ischemic attack (TIA) is a cerebrovascular disease with temporary (<24 h) neurological symptoms. The symptoms of TIA patients are largely similar to those of ischemic stroke patients and include unilateral limb weakness, speech disturbances, sensory symptoms, visual disturbances, and gait difficulties. As these symptoms are transient, they are frequently evaluated based on patients' subjective reports, which are less precise than those of patients with stroke whose longer-lasting symptoms and signs can be reliably assessed by physicians. Some symptoms, such as monocular blindness, are much more common in TIA than in stroke, and limb shaking occurs almost exclusively in TIA patients. On the other hand, symptoms like hemivisual field defects or limb ataxia are underappreciated in TIA patients. These transient neurological symptoms are not necessarily caused by cerebrovascular diseases, but can be produced by a variety of non-vascular diseases. Careful history taking, examination, and appropriate imaging tests are needed to differentiate these TIA mimics from TIA. Each TIA symptom has a different specificity and sensitivity, and there has been an effort to assess the outcome of the patients through the use of specific clinical features. On top of this, recent developments in imaging techniques have greatly enhanced our ability to predict the outcomes of TIA patients. Perception or recognition of TIA symptoms may differ according to the race, sex, education, and specialty of physicians. Appropriate education of both the general population and physicians with regard to TIA symptoms is important as TIAs need emergent evaluation and treatment. PMID:24157558

  10. Stem cell therapy in ischemic stroke

    PubMed Central

    Misra, Vivek; Ritchie, Michael M.; Stone, Laura L.; Low, Walter C.

    2012-01-01

    Objective: Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. Method: We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. Result: The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Conclusions: Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke. PMID:23008400

  11. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

    PubMed Central

    Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.

    2015-01-01

    Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. Materials and Methods This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Results Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. Conclusion For all patients a considerable region of the CTP ischemic core

  12. Growth factors in ischemic stroke

    PubMed Central

    Lanfranconi, S; Locatelli, F; Corti, S; Candelise, L; Comi, G P; Baron, P L; Strazzer, S; Bresolin, N; Bersano, A

    2011-01-01

    Abstract Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects. PMID:20015202

  13. In-Hospital Ischemic Stroke

    PubMed Central

    2015-01-01

    Between 2.2% and 17% of all strokes have symptom onset during hospitalization in a patient originally admitted for another diagnosis or procedure. These in-hospital strokes represent a unique population with different risk factors, more mimics, and substantially worsened outcomes compared to community-onset strokes. The fact that these strokes manifest during the acute care hospitalization, in patients with higher rates of thrombolytic contraindications, creates distinct challenges for treatment. However, the best evidence suggests benefit to treating appropriately selected in-hospital ischemic strokes with thrombolysis. Evidence points toward a “quality gap” for in-hospital stroke with longer in-hospital delays to evaluation and treatment, lower rates of evaluation for etiology, and decreased adherence to consensus quality process measures of care. This quality gap for in-hospital stroke represents a focused opportunity for quality improvement. PMID:26288675

  14. Ischemic perinatal stroke: challenge and opportunities.

    PubMed

    Raju, Tonse N K

    2008-08-01

    The second highest risk group for developing a cerebral stroke is the perinatal period, generally defined as 20 weeks of gestation through 28th postnatal day of age. In this commentary, a brief overview of ischemic perinatal strokes is presented. Ischemic perinatal stroke (IPS) occurs at a rate of 1 : 2300 to 1 : 5000 births, accounting for 30% of children with hemiplegic cerebral palsy (CP). Thus, IPS is the most common known cause for CP [1-3]. Although they occur frequently, much remains to be studied about perinatal strokes in general and the ischemic variety in particular. PMID:18705894

  15. Post-ischemic diastolic dysfunction.

    PubMed

    Marsch, S C; Dalmas, S; Philbin, D M; Wanigasekera, V A; Ryder, W A; Wong, L S; Foëx, P

    1994-12-01

    Though a sustained post-ischemic decrease in contractile function has been clearly established, post-ischemic diastolic function has not been thoroughly investigated. Accordingly, 11 anesthetized (isoflurane 1%) open-chest beagles were instrumented to measure left ventricular pressure and dimensions (circumferential length and wall thickness) in an apicoanterior area supplied by the left anterior descending coronary artery (LAD). Pressure-dimension relations were modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 minutes partial occlusion of the LAD (systolic bulging), and 60 minutes after the onset of reperfusion. Stiffness constants were derived from the end-diastolic pressure-length and stress-strain relations, respectively. Myocardial ischemia was associated with significant (P < 0.05) alterations of the following parameters of diastolic function: (1) 47% increase in end-diastolic pressure; (2) 22% decrease in peak negative dP/dt; (3) 9% increase in the time constant of isovolumic relaxation (tau); (4) postcystolic contraction; (5) 6% increase in end-diastolic length and 10% decrease in end-diastolic thickness; (6) 12% increase in unstressed length (creep) and 13% decrease in unstressed thickness; (7) 51% increase in chamber stiffness and a 63% increase in myocardial stiffness; and (8) 40% decrease in the peak lengthening rate. After 60 minutes of reperfusion, only end-diastolic pressure and tau had returned to baseline values whereas systolic shortening fraction, postsystolic contraction, and end-diastolic and unstressed dimensions had only partially recovered. No recovery occurred in peak negative dP/dt, chamber stiffness, myocardial stiffness, and peak lengthening rate. Thus, both myocardial ischemia and reperfusion are associated with complex changes in global and regional left ventricular diastolic function. PMID:7880987

  16. Neuroprotective Mechanisms of Taurine against Ischemic Stroke

    PubMed Central

    Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

    2013-01-01

    Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429

  17. Molecular Mechanisms of Renal Ischemic Conditioning Strategies.

    PubMed

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J; Krogstrup, Nicoline V; Oltean, Mihai; Jespersen, Bente; Dor, Frank J M F

    2015-01-01

    Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized. PMID:26330099

  18. Neuroimaging in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Krishnan, Pradeep; Shroff, Manohar

    2016-09-01

    Magnetic resonance (MR) imaging is emerging as one of the most important tools in identifying the etiology of neonatal encephalopathy as well as in predicting long-term outcomes. This makes it imperative to have a broader understanding of normal myelination of the neonatal brain on MR imaging and to be familiar with the spectrum of imaging features in ischemic and non-ischemic neonatal encephalopathy. Hypoxic ischemic injury (HIE) is one of the most common causes of neonatal encephalopathy and imaging appearances are influenced by factors such as the stage of maturation of the neonatal brain and severity as well as duration of ischemic insult. Other common causes of neonatal encephalopathy include infectious diseases, congenital disorders and inborn errors of metabolism. PMID:26909496

  19. Ischemic Conditioning: Implications for Emergency Medicine.

    PubMed

    Frumkin, Kenneth; Bloom, Adam S

    2016-09-01

    Ischemic conditioning refers to the ability of brief episodes of controlled hypoperfusion around the time of an acute ischemic event to protect the target organ from reperfusion injury. A considerable body of literature suggests that interventions as simple and safe as repetitively inflating a blood pressure cuff could reduce the size and long-term morbidity of myocardial and cerebral infarction. This review introduces and summarizes the body of evidence contributing to these impressions. PMID:26973174

  20. Transient central diabetes insipidus following ischemic stroke.

    PubMed

    Jayaraman, Muthukrishnan; Kumar, Sandeep; Ahmad, F M H

    2013-10-01

    Central Diabetes Insipidus (CDI) following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery. PMID:24251140

  1. Chinese Herbal Products for Ischemic Stroke.

    PubMed

    Hung, I-Ling; Hung, Yu-Chiang; Wang, Lin-Yi; Hsu, Sheng-Feng; Chen, Hsuan-Ju; Tseng, Ying-Jung; Kuo, Chun-En; Hu, Wen-Long; Li, Tsai-Chung

    2015-01-01

    Traditional Chinese herbal products (CHPs) have been described in ancient medicine systems as treatments for various stroke-associated ailments. This study is aimed to investigate the prescription patterns and combinations of CHPs for ischemic stroke in Taiwan. Prescriptions of CHPs for ischemic stroke were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan. Every prescription with a leading diagnosis of ischemic stroke made during 2000-2010 was analyzed. Descriptive statistics were applied to the pattern of co-prescriptions. Multiple logistic regression models were used to assess demographic and risk factors that are correlated with CHP use. The dataset of inpatient claims data contained information on 15,896 subjects who experienced ischemic stroke from 2000 to 2010. There was an average of 5.82 CHPs in a single prescription for subjects with ischemic stroke. Bu-yang-huan-wu-tang (BYHWT) (40.32%) was by far the most frequently prescribed formula CHP for ischemic stroke, and the most commonly used combination of two-formula-CHP was BYHWT with Shu-jin-huo-xue-tang (SJHXT) (4.40%). Dan Shen (16.50%) was the most commonly used single CHP for ischemic stroke, and the most commonly used combination of two single CHPs was Shi Chang Pua with Yuan Zhi (4.79%). We found that BYHWT and Dan Shen were the most frequently prescribed formula and single CHP for ischemic stroke, respectively. These results provide information about individualized therapy and may contribute to further pharmacologic experiments and clinical trials. PMID:26477801

  2. Therapeutic hypothermia for acute ischemic stroke.

    PubMed

    Froehler, Michael T; Ovbiagele, Bruce

    2010-04-01

    Intravenous recombinant tissue plasminogen activator remains the only US FDA-approved treatment for acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for stroke patients. Although no clinical trials have yet investigated the efficacy of therapeutic hypothermia in focal cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of cardiac arrest and newborns with hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of hypothermia in the treatment of acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of hypothermia, methodologies employed for the induction of hypothermia, results from animal models of cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of hypothermia is key and is best accomplished with a combination of ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including meperidine, buspirone and surface warming. We await the results of clinical trials to determine the utility of therapeutic hypothermia in acute ischemic stroke. If proven efficacious, hypothermia would be a welcome complement to established reperfusion therapies for ischemic stroke patients. PMID:20397832

  3. The Ischemic Stroke Genetics Study (ISGS) Protocol

    PubMed Central

    Meschia, James F; Brott, Thomas G; Brown, Robert D; Crook, Richard JP; Frankel, Michael; Hardy, John; Merino, José G; Rich, Stephen S; Silliman, Scott; Worrall, Bradford Burke

    2003-01-01

    Background The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. Methods/Design The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. Discussion The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes. PMID:12848902

  4. Angiotensinogen polymorphism and ischemic stroke risk

    PubMed Central

    Bao, Huan; Hao, Jun-Jie; Yang, Yu-Mei; Xu, Xia-Hong; Wang, Yue; Zuo, Lian; Lu, Jing; Zhang, Jing; Zhang, Yue; Xu, Si-Yi; Wang, Xuan; Li, Ying; Li, Gang

    2015-01-01

    The angiotensinogen M235T polymorphism was associated with ischemic stroke risk. However, the results were controversial. Thus, a meta-analysis was conducted. NCBI, Medline, Web of Science and Embase databases were systematically searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. There was a significant association between angiotensinogen M235T polymorphism and ischemic stroke risk (OR = 1.69; 95% CI, 1.35-2.11; P < 0.001). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with ischemic stroke in Asian (OR = 1.85; 95% CI, 1.45-2.35; P < 0.001). In the age subgroup, we found that angiotensinogen M235T polymorphism could increase both early-onset ischemic stroke risk (OR = 1.88; 95% CI, 1.33-2.43; P < 0.001) and late-onset ischemic stroke risk (OR = 1.20; 95% CI, 1.01-1.39; P = 0.04). This meta-analysis suggested that angiotensinogen M235T polymorphism was associated with ischemic stroke. PMID:26550208

  5. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  6. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  7. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

    PubMed Central

    Wan Ahmad Kamal, Wan Syazli Rodzaia; Noor, Norizal Mohd; Abdullah, Shafie

    2013-01-01

    Background Ischemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published. Methods Sixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed. Results The results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups. Conclusions In conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts. PMID:24286040

  8. Local and remote ischemic preconditioning protect against intestinal ischemic/reperfusion injury after supraceliac aortic clamping

    PubMed Central

    Erling, Nilon; de Souza Montero, Edna Frasson; Sannomiya, Paulina; Poli-de-Figueiredo (in memoriam), Luiz Francisco

    2013-01-01

    OBJECTIVES: This study tests the hypothesis that local or remote ischemic preconditioning may protect the intestinal mucosa against ischemia and reperfusion injuries resulting from temporary supraceliac aortic clamping. METHODS: Twenty-eight Wistar rats were divided into four groups: the sham surgery group, the supraceliac aortic occlusion group, the local ischemic preconditioning prior to supraceliac aortic occlusion group, and the remote ischemic preconditioning prior to supraceliac aortic occlusion group. Tissue samples from the small bowel were used for quantitative morphometric analysis of mucosal injury, and blood samples were collected for laboratory analyses. RESULTS: Supraceliac aortic occlusion decreased intestinal mucosal length by reducing villous height and elevated serum lactic dehydrogenase and lactate levels. Both local and remote ischemic preconditioning mitigated these histopathological and laboratory changes. CONCLUSIONS: Both local and remote ischemic preconditioning protect intestinal mucosa against ischemia and reperfusion injury following supraceliac aortic clamping. PMID:24473514

  9. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  10. Resveratrol and ischemic preconditioning in the brain.

    PubMed

    Raval, Ami P; Lin, Hung Wen; Dave, Kunjan R; Defazio, R Anthony; Della Morte, David; Kim, Eun Joo; Perez-Pinzon, Miguel A

    2008-01-01

    Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense research both in the cardiovascular system and the brain. Current research suggests resveratrol may enhance prognosis of neurological disorders such as, Parkinson's, Huntington's, Alzheimer's diseases and stroke. The beneficial effects of resveratrol include: antioxidation, free radical scavenger, and modulation of neuronal energy homeostasis and glutamatergic receptors/ion channels. Resveratrol directly increases sirtuin 1 (SIRT1) activity, a NAD(+) (oxidized form of nicotinamide adenine dinucleotide)-dependent histone deacetylase related to increased lifespan in various species similar to calorie restriction. We recently demonstrated that brief resveratrol pretreatment conferred neuroprotection against cerebral ischemia via SIRT1 activation. This neuroprotective effect produced by resveratrol was similar to ischemic preconditioning-induced neuroprotection, which protects against lethal ischemic insults in the brain and other organ systems. Inhibition of SIRT1 abolished ischemic preconditioning-induced neuroprotection in CA1 region of the hippocampus. Since resveratrol and ischemic preconditioning-induced neuroprotection require activation of SIRT1, this common signaling pathway may provide targeted therapeutic treatment modalities as it relates to stroke and other brain pathologies. In this review, we will examine common signaling pathways, cellular targets of resveratrol, and ischemic preconditioning-induced neuroprotection as it relates to the brain. PMID:18537630

  11. [Experimental model of ocular ischemic diseases].

    PubMed

    Kiseleva, T N; Chudin, A V

    2014-01-01

    The review presents the most common methods of modeling of retinal ischemia in vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo (a model with increased intraocular pressure, cerebral artery occlusion, chronic ligation of the carotid arteries, photocoagulation of the retinal vessels, occlusion of the central retinal artery, endothelin-1 administration). Modeling ischemic injury in rats is the most frequently used method in studies, because the blood supply of their eyes is similar to blood flow in the human eyes. Each method has its own advantages and disadvantages. Application of methods depends on the purpose of the experimental study. Currently model of ocular ischemic disease can be obtained easily by injecting vasoconstrictive drug endothelin-1. It is the most widely used method of high intraocular pressure induced ocular ischemic damage similar to glaucoma, occlusion of central retinal artery or ophthalmic artery in human. The development of experimental models of ocular ischemic diseases and detailed investigation of mechanisms of impairment of microcirculation are useful for improve the efficiency of diagnostic and treatment of ischemic diseases of retina and optic nerve. PMID:25971134

  12. Small vessel hematocrit in ischemic myocardium

    SciTech Connect

    Gumm, D.C.; Cooper, S.M.; Marcus, M.L.; Chilian, W.M.; Harrison, D.G.

    1986-03-01

    As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement of retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.

  13. Pre-ischemic exercise alleviates oxidative damage following ischemic stroke in rats.

    PubMed

    Feng, Rui; Zhang, Min; Wang, Xiao; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2014-10-01

    Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. PMID:25187848

  14. Magnetic Resonance Characterization of Ischemic Tissue Metabolism

    PubMed Central

    Cheung, Jerry S; Wang, Xiaoying; Zhe Sun, Phillip

    2011-01-01

    Magnetic resonance imaging (MRI) and spectroscopy (MRS) are versatile diagnostic techniques capable of characterizing the complex stroke pathophysiology, and hold great promise for guiding stroke treatment. Particularly, tissue viability and salvageability are closely associated with its metabolic status. Upon ischemia, ischemic tissue metabolism is disrupted including altered metabolism of glucose and oxygen, elevated lactate production/accumulation, tissue acidification and eventually, adenosine triphosphate (ATP) depletion and energy failure. Whereas metabolism impairment during ischemic stroke is complex, it may be monitored non-invasively with magnetic resonance (MR)-based techniques. Our current article provides a concise overview of stroke pathology, conventional and emerging imaging and spectroscopy techniques, and data analysis tools for characterizing ischemic tissue damage. PMID:22216079

  15. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  16. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  17. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  18. Flow Augmentation in Acute Ischemic Stroke.

    PubMed

    Yadollahikhales, Golnaz; Borhani-Haghighi, Afshin; Torabi-Nami, Mohammad; Edgell, Randall; Cruz-Flores, Salvador

    2016-01-01

    There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection. PMID:25475112

  19. Ischemic Gastropathic Ulcer Mimics Gastric Cancer

    PubMed Central

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk. PMID:27579191

  20. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    PubMed Central

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole K.

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis. PMID:26798523

  1. Obesity Exacerbates Rat Cerebral Ischemic Injury through Enhancing Ischemic Adiponectin-Containing Neuronal Apoptosis.

    PubMed

    Wu, Ming-Hsiu; Chio, Chung-Ching; Tsai, Kuen-Jer; Chang, Ching-Ping; Lin, Nan-Kai; Huang, Chao-Ching; Lin, Mao-Tsun

    2016-08-01

    A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity. Long-term exposure to high fat, "Western diet" (WD), is detrimental to ischemic brain injury. Adiponectin receptor 1 (ADR-1) activation is also shown to exacerbate ischemic neuronal death. However, it is not known whether increasing percentages of adiponectin (APN)-containing neurons attenuates ischemic neuronal apoptosis by modulating ADRS. To explore the role of APN and its ADRs in the development of acute cerebral injury, we subjected WD and control diet (CD) rats to 1 h of middle cerebral artery occlusion followed by 23 h of reperfusion. Compared with CD rats, WD rats exhibited higher levels of brain infarct, neurologic deficits, brain edema, and apoptosis of APN-containing neurons; upregulation of both ADR-1 and P38 mitogen-activated protein kinase (P38MAPK); and downregulation of ADR-2 in ischemic brain tissues including frontal cortex, striatum, and hippocampus. Increasing percentages of APN-containing neurons by baculovirus-mediated administration of APN, in addition to reducing apoptosis of APN-containing neurons in ischemic brain tissues, significantly attenuated brain infarct and edema, neurologic deficits, and altered expression of ADR-1, P38MAPK, and ADR-2 in both WD and CD group rats. These data suggest a negative correlation between percentages of APN-containing neurons and cerebral ischemic injury. Obesity could exacerbate rat cerebral ischemic injury by enhancing apoptosis of APN-containing neurons in ischemic brain tissues probably via modulating ADRs and P38MAPK. PMID:26126515

  2. Cerebral Ischemic Preconditioning: the Road So Far….

    PubMed

    Thushara Vijayakumar, N; Sangwan, Amit; Sharma, Bhargy; Majid, Arshad; Rajanikant, G K

    2016-05-01

    Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain. PMID:26081149

  3. An overview of antithrombotics in ischemic stroke.

    PubMed

    Schweickert, Patricia A; Gaughen, John R; Kreitel, Elizabeth M; Shephard, Timothy J; Solenski, Nina J; Jensen, Mary E

    2016-06-19

    The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke. PMID:27153001

  4. Ischemic Stroke during Pregnancy and Puerperium

    PubMed Central

    Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Padovani, Alessandro; Pezzini, Alessandro

    2011-01-01

    Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy. PMID:21331336

  5. Cerebrovascular ischemic events in wind instrument players.

    PubMed

    Evers, S; Altenmüller, E; Ringelstein, E B

    2000-09-26

    Two cases of ischemic stroke due to carotid artery dissection occurring during wind instrument playing, probably caused by increased intrathoracic and subsequent intrapharyngeal pressure, are presented. A review of the literature revealed three similar patients with other types of cerebrovascular events, such as paradoxical cerebral embolism due to a patent foramen ovale and spinal epidural hematoma during trumpet playing. PMID:10994010

  6. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    PubMed Central

    Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.

    2013-01-01

    Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730

  7. Systemic corticosteroids in nonarteritic ischemic optic neuropathy

    PubMed Central

    Al-Zubidi, Nagham; Zhang, Jason; Spitze, Arielle; Lee, Andrew G

    2014-01-01

    Nonarteritic ischemic optic neuropathy (NAION) is one of the most prevalent optic nerve disorders seen in ophthalmic practice. The role of corticosteroid therapy in NAION remains a highly controversial area of debate in ophthalmology. This brief review will provide an overview of the current clinical evidence on this topic as well as some comment on the medical debate. PMID:25449939

  8. Ischemic tolerance: the mechanisms of neuroprotective strategy.

    PubMed

    Lehotský, Jan; Burda, Jozef; Danielisová, Viera; Gottlieb, Miroslav; Kaplán, Peter; Saniová, Beata

    2009-12-01

    The phenomenon of ischemic tolerance perfectly describes this quote "What does not kill you makes you stronger." Ischemic pre- or postconditioning is actually the strongest known procedure to prevent or reverse neurodegeneration. It works specifically in sensitive vulnerable neuronal populations, which are represented by pyramidal neurons in the hippocampal CA1 region. However, tolerance is effective in other brain cell populations as well. Although, its nomenclature is "ischemic" tolerance, the tolerant phenotype can also be induced by other stimuli that lead to delayed neuronal death (intoxication). Moreover, the recent data have proven that this phenomenon is not limited to application of sublethal stimuli before the lethal stress but reversed arrangement of events, sublethal stress after lethal insult, is rather equally effective. A very important term is called "cross conditioning." Cross conditioning is the capability of one stressor to induce tolerance against another. So, since pre- or post-conditioners can be used plenty of harmful stimuli, hypo- or hyperthermia and some physiological compounds, such as norepinephrine, bradykinin. Delayed neuronal death is the slow development of postischemic neurodegeneration. This allows an opportunity for a great therapeutic window of 2-3 days to reverse the cellular death process. Moreover, it seems that the mechanisms of ischemic tolerance-delayed postconditioning could be used not only after ischemia but also in some other processes leading to apoptosis. PMID:19943353

  9. Gene Therapy For Ischemic Heart Disease

    PubMed Central

    Lavu, Madhav; Gundewar, Susheel; Lefer, David J.

    2010-01-01

    Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. PMID:20600100

  10. Role of thioredoxin-1 in ischemic preconditioning, postconditioning and aged ischemic hearts.

    PubMed

    D'Annunzio, Veronica; Perez, Virginia; Boveris, Alberto; Gelpi, Ricardo J; Poderoso, Juan J

    2016-07-01

    Thioredoxin is one of the most important cellular antioxidant systems known to date, and is responsible of maintaining the reduced state of the intracellular space. Trx-1 is a small cytosolic protein whose transcription is induced by stress. Therefore it is possible that this antioxidant plays a protective role against the oxidative stress caused by an increase of reactive oxygen species concentration, as occurs during the reperfusion after an ischemic episode. However, in addition to its antioxidant properties, it is able to activate other cytoplasmic and nuclear mediators that confer cardioprotection. It is remarkable that Trx-1 also participates in myocardial protection mechanisms such as ischemic preconditioning and postconditioning, activating proteins related to cellular survival. In this sense, it has been shown that Trx-1 inhibition abolished the preconditioning cardioprotective effect, evidenced through apoptosis and infarct size. Furthermore, ischemic postconditioning preserves Trx-1 content at reperfusion, after ischemia. However, comorbidities such as aging can modify this powerful cellular defense leading to decrease cardioprotection. Even ischemic preconditioning and postconditioning protocols performed in aged animal models failed to decrease infarct size. Therefore, the lack of success of antioxidants therapies to treat ischemic heart disease could be solved, at least in part, avoiding the damage of Trx system. PMID:26987940

  11. Ischemic stroke: carotid and vertebral artery disease.

    PubMed

    Vilela, P; Goulão, A

    2005-03-01

    Ischemic strokes may have distinct aetiologies, including several different intrinsic arterial pathological disorders. The diagnosis and understanding of these arterial diseases is critical for the correct management of stroke as different treatment approaches are undertaken according to the aetiology. Atherosclerosis is by far the most common arterial disease among adults, and other pathological processes include arterial dissection, small vessel disease, inflammatory and non-inflammatory vasculopathy and vasomotor disorders. In children, there are several vasculopathies responsible for vaso-occlusive disease such as sickle-cell anemia, acute regressive angiopathy and Moya-Moya disease, neurofibromatosis, dissections, vasculitis associated with intracranial and systemic infections. An overview of the major carotid and vertebral pathological diseases responsible for ischemic stroke in adults and children, highlighting the accuracy of the different imaging modalities for its diagnosis and the imaging appearance of these diseases, is given. PMID:15657789

  12. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments

    PubMed Central

    Allen, Kimberly A.; Brandon, Debra H.

    2011-01-01

    Hypoxic ischemic encephalopathy (HIE) is a serious birth complication affecting full term infants: 40–60% of affected infants die by 2 years of age or have severe disabilities. The majority of the underlying pathologic events of HIE are a result of impaired cerebral blood flow and oxygen delivery to the brain with resulting primary and secondary energy failure. In the past, treatment options were limited to supportive medical therapy. Currently, several experimental treatments are being explored in neonates and animal models to ameliorate the effects of secondary energy failure. This review discusses the underlying pathophysiologic effects of a hypoxic-ischemic event and experimental treatment modalities being explored to manage infants with HIE. Further research is needed to better understand if the long-term impact of the experimental treatments and whether the combinations of experimental treatments can improve outcomes in infants with HIE. PMID:21927583

  13. [Nuclear magnetic resonance in ischemic cardiopathy].

    PubMed

    Meave, Aloha

    2007-01-01

    Nuclear magnetic resonance is the "gold standard" technique to quantify the ventricular volume, the ejection fraction, and the myocardial mass. In patients suffering from ischemic cardiopathy, the ejection fraction is the most important prognostic parameter, even above from lessoned arteries index. An adequate diagnose between a non-viable and a viable myocardium is of great importance in the therapeutic approach for ischemic cardiopathy. By administrating a paramagnetic contrast media named gadolinium, fist pass and late-reinforcement techniques, are applied. With these, it is possible to evaluate the perfusion as well as necrotic areas. In order to identify sub-endocardium ischemia, drugs such as adenosine and dipiridamol, are employed as vasodilators. This technique allows the definition of reinforcement extension, being sub-endocardiac, which is an ailment which affects 50% of the myocardium depth, or even, transmural compromise. PMID:18938717

  14. Evolving Treatments for Acute Ischemic Stroke.

    PubMed

    Zerna, Charlotte; Hegedus, Janka; Hill, Michael D

    2016-04-29

    The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. PMID:27126651

  15. [Serious jaundice and thyrotoxic myocardiopathy with atrial thrombus].

    PubMed

    Souza, Marcus V Leitão de; Novaes, Fernanda Satake

    2012-10-01

    Jaundice related to thyrotoxicosis and not as an effect of antithyroid drugs is a rare complication that usually occurs in the presence of heart failure (HF) or hepatitis. We report a case of a 54-year-old white woman with hyperthyroidism caused by Graves's disease and jaundice despite methimazole suspension. Bilirubin fluctuated at high values, between 30.0 and 52.3 mg/dL, transaminases were slightly increased, on admission ALT = 46 U/L and AST = 87 U/L; coagulation indices and serum proteins were on the lower limit of the normal range with PT 68% and albumin = 2.5 g/dL. Serology for hepatitis was negative. After the first radioiodine therapy (RT), bilirubin reached its maximum, which coincided with the worst period of HF exacerbation. Bilirubin normalized 4 weeks after the second RT, with the stabilization of HF and normalization of thyroid hormones. We discuss the possible etiologies of severe jaundice in hyperthyroid patients, as well as the difficult anticoagulant therapy with warfarin. PMID:23108751

  16. [Pathogenetic interpretation of left ventricle obstruction in hypertrophic obstructive myocardiopathy].

    PubMed

    D'Annunzio, E; Mobilji, A; Falcone, A; D'Orazio, G; Rasetti, G; Olivieri, N; Griffi, E; Pontono, O

    1982-09-15

    Nine patients affected from IHSS have been studied by 2D-echocardiography examination. Following detected pictures the Authors try to explain the pathogenesis of the dynamic obstruction of the L.V. The Authors conclude ascribing it to the postero-medial papillary muscle that move abnormally towards the IVS. Instead the SAM could be ascribed to the chordee of the mitral value, but these are considered unable to obstruct L.V. The differences between SAM and L.V. obstruction are underlined and discussed. PMID:6213883

  17. [Peripartum myocardiopathy. A case report, diagnostic and therapeutic considerations].

    PubMed

    Camarero García, A; Chang Córdova, E; Márquez García, A; Martínez Vivas, A; Carranza Lira, S

    1998-01-01

    A case of periobstetric cardiomyopathy is presented, it was identified at 32 weeks, because of congestive cardiac failure, the obstetric event was resolved by cesarean section due to low fetal reserve, clinical and hemodynamical criteria for diagnosis are reviewed and also therapeutic alternatives are discussed. PMID:9528212

  18. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options. PMID:23091744

  19. Remote ischemic conditioning: a clinical trial's update.

    PubMed

    Candilio, Luciano; Hausenloy, Derek J; Yellon, Derek M

    2011-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. This process can, however, induce further myocardial damage, namely acute myocardial ischemia-reperfusion injury (IRI) and worsen clinical outcome. Therefore, novel therapeutic strategies are required to protect the myocardium against IRI in patients with CAD. In this regard, the endogenous cardioprotective phenomenon of "ischemic conditioning," in which the heart is put into a protected state by subjecting it to one or more brief nonlethal episodes of ischemia and reperfusion, has the potential to attenuate myocardial injury during acute IRI. Intriguingly, the heart can be protected in this manner by applying the "ischemic conditioning" stimulus to an organ or tissue remote from the heart (termed remote ischemic conditioning or RIC). Furthermore, the discovery that RIC can be noninvasively applied using a blood pressure cuff on the upper arm to induce brief episodes of nonlethal ischemia and reperfusion in the forearm has greatly facilitated the translation of RIC into the clinical arena. Several recently published proof-of-concept clinical studies have reported encouraging results with RIC, and large multicenter randomized clinical trials are now underway to investigate whether this simple noninvasive and virtually cost-free intervention has the potential to improve clinical outcomes in patients with CAD. In this review article, we provide an update of recently published and ongoing clinical trials in the field of RIC. PMID:21821533

  20. Endothelial progenitor cells in acute ischemic stroke

    PubMed Central

    Martí-Fàbregas, Joan; Crespo, Javier; Delgado-Mederos, Raquel; Martínez-Ramírez, Sergi; Peña, Esther; Marín, Rebeca; Dinia, Lavinia; Jiménez-Xarrié, Elena; Fernández-Arcos, Ana; Pérez-Pérez, Jesús; Querol, Luis; Suárez-Calvet, Marc; Badimon, Lina

    2013-01-01

    Objectives The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points. Material and methods We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0–2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry. Results We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes. Conclusions After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months. PMID:24363968

  1. Biomarkers for ischemic preconditioning: finding the responders

    PubMed Central

    Koch, Sebastian; Della-Morte, David; Dave, Kunjan R; Sacco, Ralph L; Perez-Pinzon, Miguel A

    2014-01-01

    Ischemic preconditioning is emerging as an innovative and novel cytoprotective strategy to counter ischemic vascular disease. At the root of the preconditioning response is the upregulation of endogenous defense systems to achieve ischemic tolerance. Identifying suitable biomarkers to show that a preconditioning response has been induced remains a translational research priority. Preconditioning leads to a widespread genomic and proteonomic response with important effects on hemostatic, endothelial, and inflammatory systems. The present article summarizes the relevant preclinical studies defining the mechanisms of preconditioning, reviews how the human preconditioning response has been investigated, and which of these bioresponses could serve as a suitable biomarker. Human preconditioning studies have investigated the effects of preconditioning on coagulation, endothelial factors, and inflammatory mediators as well as on genetic expression and tissue blood flow imaging. A biomarker for preconditioning would significantly contribute to define the optimal preconditioning stimulus and the extent to which such a response can be elicited in humans and greatly aid in dose selection in the design of phase II trials. Given the manifold biologic effects of preconditioning a panel of multiple serum biomarkers or genomic assessments of upstream regulators may most accurately reflect the full spectrum of a preconditioning response. PMID:24643082

  2. Immune mechanisms in cerebral ischemic tolerance

    PubMed Central

    Garcia-Bonilla, Lidia; Benakis, Corinne; Moore, Jamie; Iadecola, Costantino; Anrather, Josef

    2014-01-01

    Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies. PMID:24624056

  3. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469

  4. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions. PMID:27090751

  5. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences.

    PubMed

    Aimo, Alberto; Borrelli, Chiara; Giannoni, Alberto; Pastormerlo, Luigi Emilio; Barison, Andrea; Mirizzi, Gianluca; Emdin, Michele; Passino, Claudio

    2015-10-26

    In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy. PMID:26516416

  6. Cellular Basis of Anoxic-Ischemic Brain Injury

    PubMed Central

    Bronshvag, Michael M.

    1978-01-01

    Anoxic-ischemic cerebral disease is an important primary cause of morbidity and mortality, and also complicates a number of systemic diseases. Its clinical manifestations, such as hemiparesis and coma, represent cellular injury sustained by the complex, inhomogeneous brain. An understanding of the nature and pattern of anoxic-ischemic cerebral injury, and of the logical basis for avenues of therapy, is necessary to the management of patients with the various anoxic-ischemic disorders. PMID:685270

  7. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    PubMed Central

    Duanmu, Wang-sheng; Cao, Liu; Chen, Jing-yu; Ge, Hong-fei; Hu, Rong; Feng, Hua

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury. PMID:27212927

  8. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke

    PubMed Central

    Marsh, Elisabeth B.; Llinas, Rafael H.; Schneider, Andrea L.C.; Hillis, Argye E.; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F.

    2016-01-01

    Abstract Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe. The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation. PMID:26765425

  9. Transient ischemic attack as a medical emergency.

    PubMed

    Okada, Yasushi

    2014-01-01

    Since transient ischemic attack (TIA) is regarded as a medical emergency with high risk for early stroke recurrence, the underlying mechanisms should be immediately clarified to conclude a definitive diagnosis and provide early treatment. Early risk stratification using ABCD(2) scores can predict the risk of ischemic stroke occurring after TIA. Carotid ultrasonography (US) can evaluate the degree of stenosis, plaque properties and flow velocity of ICA lesions. High-risk mobile plaques can be classified by carotid US, and aortogenic sources of emboli can be detected by transesophageal echocardiography. Cardiac monitoring and blood findings are thought to play a key role in a diagnosis of cardioembolic TIA. Diffusion-weighted imaging (DWI)-MRI and MR angiography are also indispensable to understand the mechanism of TIA and cerebral circulation. To prevent subsequent stroke arising from TIA, antiplatelet and anticoagulant therapies should be started immediately along with comprehensive management of life-style, hypertension, diabetes mellitus, dyslipidemia and other atherosclerotic diseases. Carotid endarterectomy and endovascular intervention are critical for treating symptomatic patients with significant stenosis of ICA. A novel concept of acute cerebrovascular syndrome (ACVS) has recently been advocated to increase awareness of TIA among citizens, patients and medical professionals. TIA should be recognized as the last opportunity to avoid irreversible ischemic stroke and its sequelae. The clinical relevance of the new concept of ACVS is advocated by early recurrence after TIA, analysis of high-risk TIA, treatment strategies and the optimal management of TIA. Raising TIA awareness should also proceed across many population sectors. PMID:24157554

  10. Ischemic exercise and the muscle metaboreflex.

    PubMed

    Cornett, J A; Herr, M D; Gray, K S; Smith, M B; Yang, Q X; Sinoway, L I

    2000-10-01

    In exercising muscle, interstitial metabolites accumulate and stimulate muscle afferents. This evokes the muscle metaboreflex and raises arterial blood pressure (BP). In this report, we examined the effects of tension generation on muscle metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR), BP, P(i), H(2)PO(4)(-), and pH ((31)P-NMR spectroscopy) data were collected in 10 normal healthy men (age 23 +/- 1 yr) during rhythmic handgrip exercise. After baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2 min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was continued until near fatigue (Borg 19). Measurements were continued for an additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60% of the subjects' maximum voluntary contraction (MVC) in random order. As tension increased, the time to fatigue decreased. In addition, mean arterial pressure and HR were higher at 60% MVC than at any of the other lower tensions. The NMR data showed significantly greater increases in H(2)PO(4)(-), P(i), and H(+) at 60% than at 15 and 30% MVC. Therefore, despite the subjects working to the same perceived effort level, a greater reflex response (represented by BP and HR data) was elicited at 60% MVC than at any of the other ischemic tensions. These data are consistent with the hypothesis that, as tension increases, factors aside from insufficient blood flow contribute to the work effect on muscle metabolites and the magnitude of the reflex response. PMID:11007579

  11. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    PubMed Central

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

    2012-01-01

    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  12. [Secondary prevention of ischemic non cardioembolic stroke].

    PubMed

    Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere

    2015-01-01

    Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. PMID:25771074

  13. [Ischemic optic neuropathy after lumbar spine surgery].

    PubMed

    Bermejo-Alvarez, M A; Carpintero, M; García-Carro, G; Acebal, G; Fervienza, P; Cosío, F

    2007-12-01

    Ischemic optic neuropathy is the most common cause of visual complications after non-ophthalmic surgery. The incidence has varied in different case series, but prone-position spine surgery appears to be involved in most of the reports. We present the case of a 47-year-old woman who developed near total blindness in the left eye following lumbar spine fusion surgery involving the loss of 900 mL of blood. An ophthalmic examination including inspection of the ocular fundus, fluorescein angiography, and visual evoked potentials returned a diagnosis of retrolaminar optic neuropathy. Outcome was poor. PMID:18200998

  14. Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat.

    PubMed

    Cochrane, J; Williams, B T; Banerjee, A; Harken, A H; Burke, T J; Cairns, C B; Shapiro, J I

    1999-03-01

    Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study. PMID:10088174

  15. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells

    PubMed Central

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219

  16. Oxidative stress--assassin behind the ischemic stroke.

    PubMed

    Pradeep, Hanumanthappa; Diya, Joseph B; Shashikumar, Shivaiah; Rajanikant, Golgodu K

    2012-01-01

    Ischemic stroke is the second leading cause of death and disability worldwide and is associated with significant clinical and socioeconomic implications, emphasizing the need for effective therapies. Several neuroprotective strategies have failed in clinical trials because of poor knowledge of the molecular processes flanked with ischemic stroke. Therefore, uncovering the molecular processes involved in ischemic brain injury is of critical importance. Therapeutic strategies for ischemic stroke remain ineffective, though rapid advances occur in understanding the pathophysiology of the disease. The oxidative stress is one such high-potential phenomenon, the precise role of which needs to be understood during ischemic events. Nevertheless, the studies carried out in preclinical models of ischemic stroke have pointed to the major role of oxidative stress in exacerbating the ischemic injury. Oxidative stress leading to cell death requires generation of free radicals through multiple mechanisms, such as respiratory inhibition, Ca(2+) imbalance, excitotoxicity, reperfusion injury and inflammation. Free radicals are highly reactive to all the molecular targets: lipids, proteins and nucleic acids, modifying their chemical structure and generating oxidation-derived products. This review discusses molecular aspects of oxidative stress in ischemic stroke and catastrophes that set up as an aftermath of the trauma. PMID:23023336

  17. REMOTE ISCHEMIC CONDITIONING INFLUENCES MITOCHONDRIAL DYNAMICS

    PubMed Central

    Cellier, Laura; Tamareille, Sophie; Kalakech, Hussein; Guillou, Sophie; Lenaers, Guy; Prunier, Fabrice; Mirebeau-Prunier, Delphine

    2016-01-01

    ABSTRACT Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission. Interventions that decrease mitochondrial fission or increase mitochondrial fusion have been associated with reduced I/R injury. However, whether RIPC influences mitochondrial dynamics or not has yet to be ascertained. We sought to determine the role played by mitochondrial dynamics in RIPC-induced cardioprotection. Male adult rats exposed in vivo to myocardial I/R were assigned to one of two groups, either undergoing 40 min of myocardial ischemia followed by 120 min of reperfusion (MI group) or four 5-min cycles of limb ischemia interspersed by 5 min of limb reperfusion, immediately prior to myocardial ischemia and 120 min of reperfusion (MI+RIPC group). After reperfusion, infarct size was assessed and myocardial tissue was analyzed by Western blot and electron microscopy. RIPC induced smaller infarct size (−28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology. These findings suggest that mitochondrial dynamics play a role in the mechanisms of RIPC-induced cardioprotection. PMID:26555744

  18. Metabolic Prosthesis for Oxygenation of Ischemic Tissue

    SciTech Connect

    Greenbaum, Elias

    2009-01-01

    This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer, suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.

  19. Creatine kinase in ischemic and inflammatory disorders.

    PubMed

    Kitzenberg, David; Colgan, Sean P; Glover, Louise E

    2016-12-01

    The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies. PMID:27527620

  20. Atypical and ischemic features of embolized meningiomas.

    PubMed

    Matsuda, Ken; Takeuchi, Hiroaki; Arai, Yoshikazu; Kitai, Ryuhei; Hosoda, Tetsuya; Tsunetoshi, Kenzo; Arishima, Hidetaka; Sato, Kazufumi; Kikuta, Ken-Ichiro

    2012-01-01

    Preoperative embolization (POE) of meningiomas is widely used to facilitate surgical removal and to reduce intraoperative blood loss. The resulting necrosis and enhanced proliferation have been reported to affect subsequent histologic grading. However, there was little concern about ischemic features, for example small cells resembling atypical meningiomas, cytoplasmic vacuoles resembling clear cell meningioma, intercellular discohesion resembling rhabdoid meningioma, and perivascular cuffs resembling papillary meningioma. Therefore, the extent of these ischemic features was scored and Ki-67 staining indices were investigated in a POE group composed of 29 specimens of meningiomas treated with POE and compared with equivalent results for a non-POE group composed of 29 meningiomas that were not treated with POE. Small cells with high N/C ratios, cytoplasmic vacuoles, intercellular discohesion, and perivascular cuffs were significantly increased in the POE group (versus the non-POE group, p < 0.05). There were no significant differences of the Ki-67 index between the POE group (2.2%) and the non-POE group (1.9%) (p = 0.49). Our results suggest that small cell change resulting in necrosis may be followed by POE, and that clear cell-like, rhabdoid cell-like, or pseudopapillary pattern identified in meningiomas may also be induced by POE. Therefore, histological findings and determination of grading should be evaluated cautiously in cases of embolized meningiomas. PMID:21789536

  1. Ischemic nephropathy: detection and therapeutic intervention.

    PubMed

    García-Donaire, José A; Alcázar, José M

    2005-12-01

    Although the real prevalence of ischemic nephropathy as a cause of end-stage renal disease is unknown, its incidence has increased in past years. The diagnosis of this pathology requires that a number of functional and anatomic tests be carried out. The initial approach should be to perform duplex Doppler ultrasonography which, besides providing data on the size and extent of the stenosis, enables the intrarenal resistive index to be estimated to determine the pattern of renal parenchyma injury and the expected progression if revascularized. The most frequently used morphologic techniques are magnetic resonance angiography and computer tomography angiography. In the event of ischemic neuropathy, it is necessary to perform a renal arteriography regardless of the inherent risks of contrast toxicity or atheroembolism. Various therapeutic options are reviewed, with emphasis on percutaneous transluminal renal angiography plus stent as the first indication. Even though initial reports were contradictory, several meta-analyses have concluded that better blood pressure control and renal function improvement are achieved with percutaneous transluminal renal angiography plus stent than with conventional medical therapy. Surgical revascularization is preferable in patients with severe aorto-iliac pathology and renal artery ostium complete thrombosis. The risks and benefits of these procedures must be evaluated on an individual basis. PMID:16336566

  2. Mitral valve function following ischemic cardiomyopathy: a biomechanical perspective

    PubMed Central

    Rim, Yonghoon; McPherson, David D.; Kim, Hyunggun

    2014-01-01

    Ischemic mitral valve (MV) is a common complication of pathologic remodeling of the left ventricle due to acute and chronic coronary artery diseases. It frequently represents the pathologic consequences of increased tethering forces and reduced coaptation of the MV leaflets. Ischemic MV function has been investigated from a biomechanical perspective using finite element-based computational MV evaluation techniques. A virtual 3D MV model was created utilizing 3D echocardiographic data in a patient with normal MV. Two types of ischemic MVs containing asymmetric medial-dominant or symmetric leaflet tenting were modeled by altering the configuration of the normal papillary muscle (PM) locations. Computational simulations of MV function were performed using dynamic finite element methods, and biomechanical information across the MV apparatus was evaluated. The ischemic MV with medial-dominant leaflet tenting demonstrated distinct large stress distributions in the posteromedial commissural region due to the medial PM displacement toward the apical-medial direction resulting in a lack of leaflet coaptation. In the ischemic MV with balanced leaflet tenting, mitral incompetency with incomplete leaflet coaptation was clearly identified all around the paracommissural regions. This computational MV evaluation strategy has the potential for improving diagnosis of ischemic mitral regurgitation and treatment of ischemic MVs. PMID:24211876

  3. Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice

    PubMed Central

    Zou, Dingquan; Zhan, Lei; Li, Zhengxi; Zhu, Wan; Su, Hua

    2016-01-01

    Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2RFP/+Cx3cr1GFP/+ mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene. Behavior was tested 3 days after pMCAO. Infarct volume, the number of CD68+ cells, apoptotic neurons, bone marrow-derived macrophages (RFP+), and microgila (GFP+) in the peri-infarct region were quantified. Compared to mice subjected to pMCAO only, bone fracture 6 or 24 hours before pMCAO increased behavioral deficits, the infarct volume, and the number of CD68+ cells and apoptotic neurons in the peri-infarct area. Both bone marrow-derived macrophages (CCR2+) and microglia (CX3CR1+) increased in the peri-infarct regions of mice subjected to bone fracture before pMCAO compared to stroke-only mice. The mice subjected to bone fracture 6 hours before pMCAO had more severe injury than mice that had bone fracture 24 hours before pMCAO. Our data showed that bone fracture shortly before stroke also increases neuroinflammation and exacerbates ischemic cerebral injury. Our findings suggest that inhibition of neuroinflammation or management of stroke risk factors before major bone surgery would be beneficial for patients who are likely to suffer from stroke. PMID:27089041

  4. Irradiation-related ischemic heart disease

    SciTech Connect

    Corn, B.W.; Trock, B.J.; Goodman, R.L. )

    1990-04-01

    An expectation for long-term survival has emerged among several groups of cancer patients treated with therapeutic irradiation (eg, Hodgkin's disease, early stage breast cancer). Therefore, the cardiovascular sequelae of thoracic irradiation have recently come under scrutiny. Animal models have demonstrated that cardiac irradiation can directly damage the myocardial microvasculature and can indirectly damage the coronary macrovasculature when coupled with cholesterol feeding. A clear association between thoracic radiotherapy and ischemic heart disease was observed among older clinical studies using radiotherapeutic techniques that are no longer optimal by today's standards. Such a relationship could not be confirmed in modern studies in which treatment factors (such as dose and volume of heart irradiated) were more carefully controlled. 56 references.

  5. [Ischemic stroke following a scorpion sting].

    PubMed

    Elkhayari, M; Hachimi, A; Ziadi, A; Abdenasser Samkaoui, M

    2013-01-01

    Scorpion envenomation is caused by an accidental scorpion sting. In its severe form, it involves life-threatening respiratory or cardiac damage; it may also cause the neurological severity of systemic manifestations. We report the case of a young 35-year-old woman stung by an Androctonus mauretanicus scorpion, who developed impaired consciousness, hemiplegia and respiratory distress. At admission, the brain computed tomography showed a hypodense area in the right parietal region; the chest radiograph revealed a bilateral alveolar syndrome. Troponin was elevated and hemostasis disorders were present. The clinical course was remarkable: cardiogenic shock with multiple organ failure followed by death on day 3. This case illustrates a rare complication of scorpion envenomation: ischemic stroke due to an undetermined mechanism, which in addition to the cardiac and respiratory injuries, led to the serious complications and fatal outcome. PMID:23648127

  6. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

  7. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  8. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Dixon, Brandon J; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  9. PAD in women: the ischemic continuum.

    PubMed

    Pollak, Amy West

    2015-06-01

    Lower extremity peripheral arterial disease (PAD) is part of the ischemic continuum of atherosclerotic vascular disease and is associated with an increased risk of myocardial infarction, stroke, and cardiovascular death. Compared to men, women with PAD are more likely to have asymptomatic disease or atypical symptoms. PAD in women is associated with decreased exercise capacity, reduced quality of life, increased risk of depression, as well as a greater risk of acute cardiovascular events and cardiovascular mortality than male counterparts. Ensuring an appropriate diagnosis of women with PAD offers an opportunity to begin risk factor modification therapy, improve walking capacity and make a timely referral for revascularization if needed. It is critical to highlight the sex-based disparities in lower extremity PAD so that we may work to improve outcomes for women with PAD. PMID:25939674

  10. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    PubMed Central

    Shaafi, Sheyda; Mahmoudi, Javad; Pashapour, Ali; Farhoudi, Mehdi; Sadigh-eteghad, Saeed; Akbari, Hossein

    2014-01-01

    Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries. PMID:25671178

  11. Leukocyte Recruitment and Ischemic Brain Injury

    PubMed Central

    Yilmaz, Gokhan

    2010-01-01

    Leukocytes are recruited into the cerebral microcirculation following an ischemic insult. The leukocyte–endothelial cell adhesion manifested within a few hours after ischemia (followed by reperfusion, I/R) largely reflects an infiltration of neutrophils, while other leukocyte populations appear to dominate the adhesive interactions with the vessel wall at 24 h of reperfusion. The influx of rolling and adherent leukocytes is accompanied by the recruitment of adherent platelets, which likely enhances the cytotoxic potential of the leukocytes to which they are attached. The recruitment of leukocytes and platelets in the postischemic brain is mediated by specific adhesion glycoproteins expressed by the activated blood cells and on cerebral microvascular endothelial cells. This process is also modulated by different signaling pathways (e.g., CD40/CD40L, Notch) and cytokines (e.g., RANTES) that are activated/released following I/R. Some of the known risk factors for cardiovascular disease, including hypercholesterolemia and obesity appear to exacerbate the leukocyte and platelet recruitment elicited by brain I/R. Although lymphocyte–endothelial cell and –platelet interactions in the postischemic cerebral microcirculation have not been evaluated to date, recent evidence in experimental animals implicate both CD4+ and CD8+ T-lymphocytes in the cerebral microvascular dysfunction, inflammation, and tissue injury associated with brain I/R. Evidence implicating regulatory T-cells as cerebroprotective modulators of the inflammatory and tissue injury responses to brain I/R support a continued focus on leukocytes as a target for therapeutic intervention in ischemic stroke. PMID:19579016

  12. Green Space and Mortality Following Ischemic Stroke

    PubMed Central

    Wilker, Elissa H.; Wu, Chih-Da; McNeely, Eileen; Mostofsky, Elizabeth; Spengler, John; Wellenius, Gregory A.; Mittleman, Murray A.

    2014-01-01

    Background Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival has not been studied. Methods Patients ≥21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and 2008 with acute ischemic stroke were identified. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. Addresses were linked to average Normalized Difference Vegetation Index, distance to roadways with more than 10,000 cars/day, and US census block group. Deaths were identified through June 2012 using the Social Security Death Index. Results There were 929 deaths among 1,645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history, demographic and socioeconomic factors, the hazard ratio for patients living in locations in the highest quartile of green space compared to the lowest quartile was 0.78 (95% Confidence Interval: 0.63 to 0.97) (p-trend=0.009). This association remained statistically significant after adjustment for residential proximity to a high traffic road. Conclusions Residential proximity to green space is associated with higher survival rates after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association, and to better understand the exposure-response relationships and susceptibility factors that may contribute to higher mortality in low green space areas. PMID:24906067

  13. Pre-ischemic treadmill training for prevention of ischemic brain injury via regulation of glutamate and its transporter GLT-1.

    PubMed

    Yang, Xiaojiao; He, Zhijie; Zhang, Qi; Wu, Yi; Hu, Yongshan; Wang, Xiaolou; Li, Mingfen; Wu, Zhiyuan; Guo, Zhenzhen; Guo, Jingchun; Jia, Jie

    2012-01-01

    Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC)-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1) protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate. PMID:22949807

  14. Sexual dimorphism in ischemic stroke: lessons from the laboratory

    PubMed Central

    Manwani, Bharti; McCullough, Louise D

    2011-01-01

    Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms. PMID:21612353

  15. The Migraine-Ischemic Stroke Relation in Young Adults

    PubMed Central

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2011-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

  16. Fatty acids, membrane viscosity, serotonin and ischemic heart disease

    PubMed Central

    2010-01-01

    Novel markers for ischemic heart disease are under investigation by the scientific community at international level. This work focuses on a specific platelet membrane fatty acid condition of viscosity which is linked to molecular aspects such as serotonin and G proteins, factors involved in vascular biology. A suggestive hypothesis is considered about the possibility to use platelet membrane viscosity, in relation to serotonin or, indirectly, the fatty acid profile, as indicator of ischemic risk. PMID:20825633

  17. Inhibition of HDAC2 Protects the Retina From Ischemic Injury

    PubMed Central

    Fan, Jie; Alsarraf, Oday; Dahrouj, Mohammad; Platt, Kenneth A.; Chou, C. James; Rice, Dennis S.; Crosson, Craig E.

    2013-01-01

    Purpose. Protein acetylation is an essential mechanism in regulating transcriptional and inflammatory events. Studies have shown that nonselective histone deacetylase (HDAC) inhibitors can protect the retina from ischemic injury in rats. However, the role of specific HDAC isoforms in retinal degenerative processes remains obscure. The purpose of this study was to investigate the role of HDAC2 isoform in a mouse model of ischemic retinal injury. Methods. Localization of HDAC2 in mice retinas was evaluated by immunohistochemical analyses. To investigate whether selective reduction in HDAC2 activity can protect the retina from ischemic injury, Hdac2+/− mice were utilized. Electroretinographic (ERG) and morphometric analyses were used to assess retinal function and morphology. Results. Our results demonstrated that HDAC2 is primarily localized in nuclei in inner nuclear and retinal ganglion cell layers, and HDAC2 activity accounted for approximately 35% of the total activities of HDAC1, 2, 3, and 6 in the retina. In wild-type mice, ERG a- and b-waves from ischemic eyes were significantly reduced when compared to pre-ischemia baseline values. Morphometric examination of these eyes revealed significant degeneration of inner retinal layers. In Hdac2+/− mice, ERG a- and b-waves from ischemic eyes were significantly greater than those measured in ischemic eyes from wild-type mice. Morphologic measurements demonstrated that Hdac2+/− mice exhibit significantly less retinal degeneration than wild-type mice. Conclusions. This study demonstrated that suppressing HDAC2 expression can effectively reduce ischemic retinal injury. Our results support the idea that the development of selective HDAC2 inhibitors may provide an efficacious treatment for ischemic retinal injury. PMID:23696608

  18. Trans Fat, Aspirin, and Ischemic Stroke in Postmenopausal Women

    PubMed Central

    Yaemsiri, Sirin; Sen, Souvik; Tinker, Lesley; Rosamond, Wayne; Wassertheil-Smoller, Sylvia; He, Ka

    2012-01-01

    Objective To examine the associations between dietary fat intake and ischemic stroke among postmenopausal women. Methods We conducted a prospective cohort study of 87,025 generally healthy postmenopausal women (age 50–79 years) enrolled in the Women’s Health Initiative Observational Study. Repeated and validated dietary assessments were done using a self-administered food frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HR) of ischemic stroke based on quintiles of the cumulative average of fat intake. Results We documented 1,049 incident cases of ischemic stroke over 663,041 person-years of follow-up. Women in the highest quintile of trans fat intake had a significantly higher incidence of ischemic stroke (HR 1.39, 95% confidence interval [CI] 1.08–1.79, P-trend = 0.048) compared with women in the lowest quintile, while controlling for multiple covariates. The observed association was modified by aspirin use (P-interaction=0.02). The HR was 1.66 (95% CI 1.21–2.36, P-trend<0.01) among baseline non-aspirin users (n=67,288) and 0.95 (95% CI 0.60–1.48, P-trend=0.43) among aspirin users (n=19,736). No significant associations were found between intakes of saturated, monounsaturated, or polyunsaturated fat and ischemic stroke or any ischemic stroke subtypes. Interpretation In this large cohort of postmenopausal women, higher intake of trans fat was associated with incident ischemic stroke independent of major lifestyle/dietary factors. Aspirin use may attenuate the potential adverse effect of trans fat intake on ischemic stroke. PMID:22383309

  19. Systemic chemokine levels, coronary heart disease, and ischemic stroke events

    PubMed Central

    Canouï-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.

    2011-01-01

    Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors. PMID:21849651

  20. Progressive "vascular" corticobasal syndrome due to bilateral ischemic hemispheric lesions.

    PubMed

    Kim, Young-Do; Kim, Joong-Seok; Lee, Eek-Sung; Yang, Dong-Won; Lee, Kwang-Soo; Kim, Yeong-In

    2009-01-01

    We report a patient that presented with the corticobasal syndrome (CBS), including progressive dementia, asymmetric parkinsonism associated with constructional and ideomotor apraxia, action myoclonus and focal hand dystonia. Magnetic resonance imaging of the brain revealed extensive ischemic lesions in both fronto-temporo-parieto-occipital lobes and steno-occlusion of the middle cerebral arteries, bilaterally. This case illustrates that extensive cortical vascular-ischemic lesions may present with symptoms mimicking the corticobasal syndrome. PMID:19755778

  1. In vivo characterization of ischemic small intestine using bioimpedance measurements.

    PubMed

    Strand-Amundsen, R J; Tronstad, C; Kalvøy, H; Gundersen, Y; Krohn, C D; Aasen, A O; Holhjem, L; Reims, H M; Martinsen, Ø G; Høgetveit, J O; Ruud, T E; Tønnessen, T I

    2016-02-01

    The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia. PMID:26805916

  2. Polygenic risk of ischemic stroke is associated with cognitive ability

    PubMed Central

    Malik, Rainer; Marioni, Riccardo; Campbell, Archie; Seshadri, Sudha; Worrall, Bradford B.; Sudlow, Cathie L.M.; Hayward, Caroline; Bastin, Mark E.; Starr, John M.; Porteous, David J.; Wardlaw, Joanna M.; Deary, Ian J.

    2016-01-01

    Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. Results: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = −0.070, p = 1.95 × 10−8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. Conclusions: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability. PMID:26695942

  3. The Many Roles of Statins in Ischemic Stroke

    PubMed Central

    Zhao, Jingru; Zhang, Xiangjian; Dong, Lipeng; Wen, Ya; Cui, Lili

    2014-01-01

    Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke. PMID:25977681

  4. Clinical and morphological correlations in acute ischemic stroke.

    PubMed

    Slujitoru, Anca Stefania; Enache, Andreea Lorena; Pintea, Irina Lavinia; Rolea, Elisabeta; Stocheci, Cristina Mariana; Pop, O T; Predescu, Anca

    2012-01-01

    We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made. PMID:23303014

  5. The Paradox Role of Regulatory T Cells in Ischemic Stroke

    PubMed Central

    Li, Min; Jiang, Yongjun

    2013-01-01

    The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke. PMID:24288462

  6. Relationship Between Ischemic Heart Disease and Sexual Satisfaction

    PubMed Central

    Afra, Leila Ghanbari; Taghadosi, Mohsen; Gilasi, Hamid Reza

    2016-01-01

    Aim: Ischemic heart disease is a life-threatening condition. Considerable doubts exist over the effects of this disease on patients’ sexual activity and satisfaction. The aim of this study was to evaluate the relationship between ischemic heart disease and sexual satisfaction. Methods: In a retrospective cohort study, the convenience sample of 150 patients exposure with ischemic heart disease and 150 people without exposure it was drawn from Shahid Beheshti hospital, Kashan, Iran. Sampling was performed from March to September 2014. We employed the Larson’s Sexual Satisfaction Questionnaire for gathering the data. Data were analyzed using descriptive statistics and Chi-square, t-test and linear regression analysis. Results: The means of sexual satisfaction in patients exposure with ischemic heart disease and among the subjects without exposure it were 101.47±13.42 and 100.91±16.52, respectively. There was no significant difference between the two groups regarding sexual satisfaction. However, sexual satisfaction was significantly correlated with gender and the use of cardiac medications (P value < 0.05). Conclusion: The level of sexual satisfaction in patients with exposure ischemic heart disease is similar to the people without exposure it. Moreover, the men and the patients who do not receive cardiac medications have higher levels of sexual satisfaction. Nurses who are providing care to patients with ischemic heart disease need to pay closer attention to patient education about sexual issues. PMID:26234982

  7. Therapeutic hypothermia and ischemic stroke: A literature review

    PubMed Central

    Tahir, Rizwan A.; Pabaney, Aqueel H.

    2016-01-01

    Background: Ischemic stroke is the fifth leading cause of death in the US. Clinical techniques aimed at helping to reduce the morbidity associated with stroke have been studied extensively, including therapeutic hypothermia. In this study, the authors review the literature regarding the role of therapeutic hypothermia in ischemic stroke to appreciate the evolution of hypothermia technology over several decades and to critically analyze several early clinical studies to validate its use in ischemic stroke. Methods: A comprehensive literature search was performed using PubMed and Google Scholar databases. Search terms included “hypothermia and ischemic stroke” and “therapeutic hypothermia.” A comprehensive search of the current clinical trials using clinicaltrials.gov was conducted using the keywords “stroke and hypothermia” to evaluate early and ongoing clinical trials utilizing hypothermia in ischemic stroke. Results: A comprehensive review of the evolution of hypothermia in stroke and the current status of this treatment was performed. Clinical studies were critically analyzed to appreciate their strengths and pitfalls. Ongoing and future registered clinical studies were highlighted and analyzed compared to the reported results of previous trials. Conclusion: Although hypothermia has been used for various purposes over several decades, its efficacy in the treatment of ischemic stroke is debatable. Several trials have proven its safety and feasibility; however, more robust, randomized clinical trials with large volumes of patients are needed to fully establish its utility in the clinical setting. PMID:27313963

  8. Surgical Treatment of Moderate Ischemic Mitral Regurgitation

    PubMed Central

    Smith, P.K.; Puskas, J.D.; Ascheim, D.D.; Voisine, P.; Gelijns, A.C.; Moskowitz, A.J.; Hung, J.W.; Parides, M.K.; Ailawadi, G.; Perrault, L.P.; Acker, M.A.; Argenziano, M.; Thourani, V.; Gammie, J.S.; Miller, M.A.; Pagé, P.; Overbey, J.R.; Bagiella, E.; Dagenais, F.; Blackstone, E.H.; Kron, I.L.; J., D.; Rose, E.A.; Moquete, E.G.; Jeffries, N.; Gardner, T.J.; O’Gara, P.T.; Alexander, J.H.; Michler, R.E.

    2015-01-01

    BACKGROUND Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, −9.4 and −9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P = 0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P = 0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P = 0.002), and more neurologic events (P = 0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was

  9. Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Guo, Yan; Johnson, Mary A.; Mehrabian, Zara; Mishra, Manoj K.; Kannan, Rangaramanujam; Miller, Neil R.; Bernstein, Steven L.

    2016-01-01

    Introduction Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment. Methods NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION. Results Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats. Conclusions Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia. PMID:27128315

  10. Perfusion Angiography in Acute Ischemic Stroke.

    PubMed

    Scalzo, Fabien; Liebeskind, David S

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and T max, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  11. The Apexcardiogram in Ischemic Heart Disease

    PubMed Central

    Wayne, Howard H.

    1972-01-01

    The apexcardiogram (acg), when recorded serially in patients with acute myocardial infarction (ami), preinfarction angina (pia) and stable ischemic heart disease (ihd), appeared to reflect the abnormal patterns of contraction of the left ventricle in these conditions. Thus, paradoxical bulging (dyskinesis) of the systolic wave or increased “a” wave amplitude with gradual recovery over several weeks was found in all 60 patients with documented ami and in 18 of 20 patients with pia. Electrocardiogram changes were noted, however, in only eight of the pia patients. Changes in the acg frequently antedated ischemia in the ecg. Paradoxical bulging of the systolic wave of the acg was additionally noted in patients during the pain of angina pectoris but this promptly disappeared after the administration of nitroglycerine. Patients with classic angina often had normal resting ecg's but abnormal resting acg's. In contrast to the relatively transient abnormalities noted above, the acg remained unchanged in most patients with stable ihd during follow-up of three months to two years. Patients undergoing coronary bypass operations, however, showed immediate improvement in the acg in the postoperative period. These results suggest the acg reflects the contractile pattern of the left ventricle, and may be an indirectly recorded ventriculogram. Its enhanced sensitivity and the earlier development of changes in comparison to the ecg make this a valuable tool in the study of patients with heart disease. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:5008498

  12. Stem Cell Therapy for Ischemic Heart Disease

    PubMed Central

    Jameel, Mohammad Nurulqadr

    2010-01-01

    Abstract Stem cell transplantation has emerged as a novel treatment option for ischemic heart disease. Different cell types have been utilized and the recent development of induced pluripotent stem cells has generated tremendous excitement in the regenerative field. Bone marrow-derived multipotent progenitor cell transplantation in preclinical large animal models of postinfarction left ventricular remodeling has demonstrated long-term functional and bioenergetic improvement. These beneficial effects are observed despite no significant engraftment of bone marrow cells in the myocardium and even lower differentiation of these cells into cardiomyocytes. It is thought to be related to the paracrine effect of these stem cells, which secrete factors that lead to long-term gene expression changes in the host myocardium, thereby promoting neovascularization, inhibiting apoptosis, and stimulating resident cardiac progenitor cells. Future studies are warranted to examine the changes in the recipient myocardium after stem cell transplantation and to investigate the signaling pathways involved in these effects. Antioxid. Redox Signal. 13, 1879–1897. PMID:20687781

  13. Human Data Supporting Glyburide in Ischemic Stroke.

    PubMed

    Sheth, Kevin N; Simard, J Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W Taylor

    2016-01-01

    The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916

  14. [Acute postop ischemic hepatitis and hypotension].

    PubMed

    Uzhva, V P

    2000-01-01

    The significance of the pronounced durable systemic arterial hypotension (SAH) in the origin of an acute postoperative ischemic hepatitis (APIH) was established, basing on the analysis of 40 clinical observations. Its occurrence is promoted by hemorrhage with 30% and more the circulating blood volume (CBV) deficiency, chronic cardiovascular system and pulmonary diseases, liver cirrhosis, shock, massive infusions of the blood and its components, the abdominal aorta atherosclerosis with stenosis of tr. coeliacus, a. hepatica. Forgoing SAH, the presence of promoting factors, jaundice, the transpherase activity raising in 3-5 times, the level of blood coagulating factors reduction, stable intestinal paresis were diagnostically significant symptoms. Experimental model of an APIH was elaborated in dogs, which occurs due to hypotension, caused by CBV reduction by 40% during two hours. The refractoriness of a. hepatica propria to the blood reinfusion was established. In the APIH occurrence threat the perftoran application in the 20 ml/kg dosage is the prophylaxis method as well as the method of the curative tactics choice. PMID:10857279

  15. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  16. Ischemic and hemorrhagic moyamoya disease in adults: CT findings

    PubMed Central

    Xie, Anming; Luo, Li; Ding, Yaojun; Li, Gongjie

    2015-01-01

    Objective: To investigate the findings of adult moyamoya disease (MD) of different types on plain CT, brain perfusion CT (CTP) and brain CT angiography (CTA). Materials and methods: A total of 48 patients with ischemic MD and hemorrhagic MD were recruited into present study, and findings were collected from plain CT, CTP and CTA. Results: The incidence of watershed or cortex stroke in ischemic MD (55.6% and 38.9%) was higher than in hemorrhagic MD (0%). The incidence of ventricle or basal ganglia stroke in hemorrhagic MD (40.0%, 43.3%) was higher than in ischemic MD (0%, 5.6%). CTP showed hypoperfusion in 11 patients, hyperperfusion in 12 and normal perfusion in 25. Ischemic MD patients were more likely to present hypoperfusion (61.1%; normal perfusion: 22.2%; hyperperfusion: 16.7%). Hemorrhagic MD patients were more likely to present normal perfusion (70%; hyperperfusion: 30%; hypoperfusion: 0%). The incidence of grade II MD in ischemic MD (27.8%) was higher than in hemorrhagic MD (6.7%). The incidences of grade IV and V MD in hemorrhagic MD (33.3% and 16.7%) were higher than in ischemic MD (16.7% and 11.0%). Conclusion: Hemorrhagic MD is dominant in adults with MD and stroke of these patients mainly occurs at the intraventricular space and basal ganglia. Ischemic MD in adults is characterized by hypoperfusion and hemorrhagic MD by normal perfusion on CTP. MD in adults is usually classified as grade II, III or IV on CTA. PMID:26885076

  17. Sensitivity of the neuroimaging techniques in ischemic stroke.

    PubMed

    Smajlović, Dzevdet; Sinanović, Osman

    2004-01-01

    The aim of this study was to investigate and compare the sensitivity and effectiveness of neuroimaging techniques in 190 patients with acute ischemic stroke. The first computed tomography (CT) scan for all patients was performed within the first 12 hours of the stroke symptoms onset. For each patient, between the third and fifth day of the hospitalization, at least one more neuroimaging procedure (CT and/or magnetic resonance imaging--MRI, and/or diffusion weighted imaging--DWI) was done. The CT scan in the first 12 hours of the stroke onset was positive in 32% of the patients; the highest number of the positive findings was in the patients with total anterior circulation infarct (52%). After 48 hours of the stroke onset second CT was positive in 85% (75/89), MRI in 93.5% (115/123), and DWI in 98.8% (79/80) patients. MRI was significantly more sensitive than CT in detection of ischemic lesion (88% vs. 72%, P=0.01), particularly in the patients with lacunar infarcts (75% vs. 50%, P=0.005). In detection of ischemic stroke 48 hours of the stroke onset the slightly higher number of strokes were detected on DWI in comparison with MRI (98.6% vs. 88.7%). According to our results, within the first 12 hours after the stroke onset, CT is reliable only for detection of considerable number of cortical ischemic strokes of the anterior cerebral circulation. After 48 hours from the stroke onset CT, MRI and DWI show high sensitivity in the detection of ischemic lesion of all clinical stroke subtypes. MRI is more sensitive in comparison with CT in detection of ischemic lesion, while DWI does not show dominance in comparison with MRI in identification of ischemic stroke after 48 hours of the symptoms onset. PMID:15628251

  18. Defining the Ischemic Penumbra using Magnetic Resonance Oxygen Metabolic Index

    PubMed Central

    An, Hongyu; Ford, Andria L.; Chen, Yasheng; Zhu, Hongtu; Ponisio, Rosana; Kumar, Gyanendra; Shanechi, Amirali Modir; Khoury, Naim; Vo, Katie D.; Williams, Jennifer; Derdeyn, Colin P.; Diringer, Michael N.; Panagos, Peter; Powers, William J.; Lee, Jin-Moo; Lin, Weili

    2015-01-01

    Background and Purpose Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel MRI approach which measures oxygen metabolic index (OMI), a parameter closely related to PET-derived cerebral metabolic rate of oxygen utilization, to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold which differentiates ischemic core from penumbra and (2) a reversible-injury threshold which differentiates penumbra from tissue not-at-risk for infarction. Methods Forty acute ischemic stroke patients underwent MRI at three time-points after stroke onset: < 4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured CBF, and an asymmetric spin echo sequence measured OEF, to derive OMI (OMI=CBF*OEF). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in three tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict: infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. Results The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for non-reperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. Conclusions OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample. PMID:25721017

  19. Premature Cardiac Contractions and Risk of Incident Ischemic Stroke

    PubMed Central

    Ofoma, Uchenna; He, Fan; Shaffer, Michele L.; Naccarelli, Gerard V.; Liao, Duanping

    2012-01-01

    Background The etiologies of ischemic stroke remain undetermined in 15% to 40% of patients. Apart from atrial fibrillation, other arrhythmias are less well-characterized as risk factors. Premature cardiac contractions are known to confer long-term cardiovascular risks, like myocardial infarction. Ischemic stroke as cardiovascular risk outcome remains a topic of interest. We examined the prospective relationships in the Atherosclerosis Risk in Communities (ARIC) study, to determine whether premature atrial (PAC) or ventricular (PVC) contractions are associated with increased risk for incident ischemic stroke. Methods and Results We analyzed 14 493 baseline stroke-free middle-aged individuals in the ARIC public-use data. The presence of PAC or PVC at baseline was assessed from 2-minute electrocardiogram. A physician-panel confirmed and classified all stroke cases. Average follow-up time was 13 years. Proportional hazards models assessed associations between premature contractions and incident stroke. PACs and PVCs were identified in 717 (4.9%) and 793 (5.5%) participants, respectively. In all, 509(3.5%) participants developed ischemic stroke. The hazard ratio (HR) (95% confidence interval [CI]) associated with PVC was 1.77 (1.30, 2.41), attenuated to 1.25 (0.91, 1.71) after adjusting for baseline stroke risk factors. The interaction between PVC and baseline hypertension was marginally significant (P=0.08). Among normotensives, having PVCs was associated with nearly 2-fold increase in the rate of incident ischemic stroke (HR 1.69; 95% CI 1.02, 2.78), adjusting for stroke risk factors. The adjusted risk of ischemic stroke associated with PACs was 1.30 (95% CI 0.92, 1.83). Conclusions Presence of PVCs may indicate an increased risk of ischemic stroke, especially in normotensives. This risk approximates risk of stroke from being black, male, or obese in normotensives from this cohort. PMID:23316293

  20. Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke

    PubMed Central

    Deng, Yi-hao; He, Hong-yun; Yang, Li-qiang; Zhang, Peng-yue

    2016-01-01

    The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains unclear. Therefore, in this study, we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for stroke. An adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery occlusion. Neuronal autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-II and cleaved caspase-3, respectively. Levels of both LC3-II and cleaved caspase-3 in the penumbra gradually increased within 5 hours post-ischemia. Thereafter, levels of both proteins declined, especially LC3-II. The cerebral infarct volume increased slowly 1–4 hours after ischemia, but subsequently increased rapidly until 5 hours after ischemia. The severity of the neurological deficit was positively correlated with infarct volume. LC3-II and cleaved caspase-3 levels were high in the penumbra within 5 hours after ischemia, and after that, levels of these proteins decreased at different rates. LC3-II levels were reduced to a very low level, but cleaved caspase-3 levels remained high 72 hours after ischemia. These results indicate that there are temporal differences in the activation status of the autophagic and apoptotic pathways. This suggests that therapeutic targeting of these pathways should take into consideration their unique temporal dynamics.

  1. Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: beyond ischemia-reperfusion injury.

    PubMed

    Camara-Lemarroy, Carlos Rodrigo

    2014-04-01

    Common gastrointestinal diseases such as radiation enteritis (RE), acute pancreatitis, inflammatory bowel diseases (IBD) and drug-induced hepatotoxicity share pathophysiological mechanisms at the molecular level, mostly involving the activation of many pathways of the immune response, ultimately leading to tissue injury. Increased oxidative stress, inflammatory cytokine release, inflammatory cell infiltration and activation and the up-regulation of inflammatory transcription factors participate in the pathophysiology of these complex entities. Treatment varies in each specific disease, but at least in the cases of RE and IBD immunosuppressors are effective. However, full therapeutic responses are not always achieved. The pathophysiology of ischemia-reperfusion (IR) injury shares many of these mechanisms. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIP). This procedure has been shown to protect the gut, pancreas and liver by modulating many of the same inflammatory mechanisms. Since RIP is safe and tolerable, and has shown to be effective in some recent clinical trials, I suggest that RIP could be used as a physiologically relevant adjunct treatment for non-ischemic gastrointestinal inflammatory conditions. PMID:24707140

  2. Potential microRNA biomarkers for acute ischemic stroke.

    PubMed

    Zeng, Ye; Liu, Jing-Xia; Yan, Zhi-Ping; Yao, Xing-Hong; Liu, Xiao-Heng

    2015-12-01

    Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT‑qPCR). Four confirmed differentially expressed miRNAs (miR‑9, ‑22, ‑23 and ‑125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR‑9, ‑30, ‑33, ‑124, ‑181, ‑218 and ‑330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA‑targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA‑targeted genes identified serve as potential therapeutic targets for acute ischemic stroke. PMID:26459744

  3. Management of Acute Hypertensive Response in Patients With Ischemic Stroke.

    PubMed

    AlSibai, Ahmad; Qureshi, Adnan I

    2016-07-01

    High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction. PMID:27366297

  4. Transient ischemic attack: Part II. Risk factor modification and treatment.

    PubMed

    Simmons, B Brent; Gadegbeku, Annette B; Cirignano, Barbara

    2012-09-15

    Interventions following a transient ischemic attack are aimed at preventing a future episode or stroke. Hypertension, current smoking, obesity, physical inactivity, diabetes mellitus, and dyslipidemia are all well-known risk factors, and controlling these factors can have dramatic effects on transient ischemic attack and stroke risk. For patients presenting within 48 hours of resolution of transient ischemic attack symptoms, advantages of hospital admission include rapid diagnostic evaluation and early intervention to reduce the risk of stroke. For long-term prevention of future stroke, the American Heart Association/American Stroke Association recommends antiplatelet agents, statins, and carotid artery intervention for advanced stenosis. Aspirin, extended-release dipyridamole/aspirin, and clopidogrel are acceptable first-line antiplatelet agents. Statins have also been shown to reduce the risk of stroke following transient ischemic attack, with maximal benefit occurring with at least a 50 percent reduction in low-density lipoprotein cholesterol level or a target of less than 70 mg per dL (1.81 mmol per L). For those with transient ischemic attack and carotid artery stenosis, carotid endarterectomy is recommended if stenosis is 70 to 99 percent, and perioperative morbidity and mortality are estimated to be less than 6 percent. PMID:23062044

  5. Diagnosis and management of ischemic heart disease.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Cervellin, Gianfranco

    2013-03-01

    Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. An early and accurate diagnosis of IHD is necessary to improve outcomes. According to recent guidelines, the diagnosis of acute myocardial infarction (AMI) is based on increased or decreased value of cardiospecific troponins with one measure exceeding the 99th percentile upper reference limit, associated with symptoms suggestive for myocardial ischemia, indicative electrocardiogram abnormalities, and evidence of recent myocardial functional impairment or intracoronary thrombosis. The recent advent of highly sensitive troponin immunoassays has represented a paradigm shift, wherein the improved analytical sensitivity has increased the negative predictive value, while contextually decreasing the diagnostic specificity of these tests. Although several additional biomarkers have been proposed as surrogate or in combination with troponins, there is little evidence that any of these will substantially improve AMI diagnosis. With regard to therapy, early mechanical (i.e., percutaneous coronary intervention, PCI) or pharmacological reperfusion should be performed early in ST-segment elevation myocardial infarction (STEMI) within 12 h of symptom onset, whereas fibrinolysis may be considered in all other circumstances. Patients undergoing primary PCI should also receive a combination of double antiplatelet therapy (i.e., aspirin and adenosine diphosphate receptor blocker), associated with parenteral anticoagulation, preferably with low-molecular-weight heparin. In analogy with STEMI, a wealth of data shows that primary early invasive strategy (i.e., PCI) and antiplatelet therapy remains the cornerstone of management of patients with non-ST segment elevation acute coronary syndrome. Stem cell-based therapy has also emerged as a potentially therapeutic option, and there are ongoing efforts among several investigators to translate basic research into clinical practice. PMID:23378254

  6. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  7. Sudden cardiac death markers in non-ischemic cardiomyopathy.

    PubMed

    Pimentel, Mauricio; Rohde, Luis Eduardo; Zimerman, André; Zimerman, Leandro Ioschpe

    2016-01-01

    Heart failure is an increasingly prevalent disease associated with high morbidity and mortality. In 30-40% of patients, the etiology is non-ischemic. In this group of patients, the implantable cardioverter-defibrillator (ICD) prevents sudden death and decreases total mortality. However, due to burden of cost, the fact that many ICD patients will never need any therapy, and possible complications involved in implant and follow-up, the device should not be implanted in every patient with non-ischemic heart failure. There is an urgent need to adequately identify patients with highest sudden death risk, in whom the implant is most cost-effective. In the present paper, the authors discuss current available tests for risk stratification of sudden cardiac death in patients with non-ischemic heart failure. PMID:27016256

  8. Perioperative ischemic injury after coronary bypass graft surgery

    SciTech Connect

    Li, W.; Hanelin, L.G.; Riggins, R.C.; Agnew, R.C.; Annest, L.S.; Anderson, R.P.

    1985-07-01

    Two hundred twelve patients who underwent isolated coronary bypass graft surgery were prospectively evaluated for perioperative ischemic injury. All patients underwent preoperative and postoperative testing with technetium 99m pyrophosphate first-pass ventriculography combined with myocardial uptake scans, 12-lead electrocardiography, and serial creatinine phosphokinase MB determination. Fifteen percent of the patients had ischemic injury with at least two test results positive, but only 4 percent had positive results of all three tests. No single test proved adequate. Enzyme levels were highly sensitive and had value as a screening test. The electrocardiogram was specific but only moderately sensitive. The single best test was the radionuclide scan with good sensitivity and no false-positive results. All three tests are required to rigorously diagnose ischemic injury.

  9. Targeting ischemic penumbra: part I - from pathophysiology to therapeutic strategy

    PubMed Central

    Liu, Shimin; Levine, Steven R.; Winn, H. Richard

    2010-01-01

    Penumbra is the viable tissue around the irreversibly damaged ischemic core. The purpose of acute stroke treatment is to salvage penumbral tissue and to improve brain function. However, the majority of acute stroke patients who have treatable penumbra are left untreated. Therefore, developing an effective non-recanalizational therapeutics, such as neuroprotective agents, has significant clinical applications. Part I of this serial review on “targeting penumbra” puts special emphases on penumbral pathophysiology and the development of therapeutic strategies. Bioenergetic intervention by massive metabolic suppression and direct energy delivery would be a promising future direction. An effective drug delivery system for this purpose should be able to penetrate BBB and achieve high local tissue drug levels while non-ischemic region being largely unaffected. Selective drug delivery to ischemic stroke penumbra is feasible and deserves intensive research. PMID:20607107

  10. Autonomic dysfunction in acute ischemic stroke: an underexplored therapeutic area?

    PubMed

    De Raedt, Sylvie; De Vos, Aurelie; De Keyser, Jacques

    2015-01-15

    Impaired autonomic function, characterized by a predominance of sympathetic activity, is common in patients with acute ischemic stroke. This review describes methods to measure autonomic dysfunction in stroke patients. It summarizes a potential relationship between ischemic stroke-associated autonomic dysfunction and factors that have been associated with worse outcome, including cardiac complications, blood pressure variability changes, hyperglycemia, immune depression, sleep disordered breathing, thrombotic effects, and malignant edema. Involvement of the insular cortex has been suspected to play an important role in causing sympathovagal imbalance, but its exact role and that of other brain regions remain unclear. Although sympathetic overactivity in patients with ischemic stroke appears to be a negative prognostic factor, it remains to be seen whether therapeutic strategies that reduce sympathetic activity or increase parasympathetic activity might improve outcome. PMID:25541326

  11. [Ischemic colitis: an uncommon manifestation in systemic lupus erythematosus].

    PubMed

    Medina, Viviana; Bulgach, Valeria; Lagandara, Pamela; Berner, Enrique

    2013-04-01

    We present the case of an adolescent with ischemic colitis, an infrequent pathology in this age group, worsened in the presence of systemic lupus erythematosus (SLE). The patient, aged 20, was diagnosed SLE at 6. She consulted for fever, abdominal pain in the side and right iliac fossa and diarrhea lasting 48 hours. It was assumed as acute gastroenteritis but given the persistent pain, incoercible vomiting and abdominal distension she was hospitalized. The abdominal X-ray showed distended loops, abundant feces, without air-fluid levels. The ultrasound showed erosions and ulcerations, edema and bleeding in the descending colon submucosal layer. The CT scan evidenced an ischemic lesion in the right colon. Ischemic colitis is a severe condition, infrequent in young individuals. Signs, symptoms, abdominal CT scan and colonoscopy are the elements of choice for the diagnosis. PMID:23568076

  12. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. PMID:24805069

  13. Toll-Like Receptors and Ischemic Brain Injury

    PubMed Central

    Gesuete, Raffaella; Kohama, Steven G.; Stenzel-Poore, Mary

    2014-01-01

    Toll-like receptors (TLRs) are master regulators of innate immunity and play an integral role in the activation of the inflammatory response during infections. In addition, TLRs influence the body’s response to numerous forms of injury. Recent data have shown that TLRs play a modulating role in ischemic brain damage after stroke. Interestingly, their stimulation prior to ischemia induces a tolerant state that is neuroprotective. This phenomenon, referred to as TLR preconditioning, is the result of reprogramming of the TLR response to ischemic injury. This review addresses the role of TLRs in brain ischemia and the activation of endogenous neuroprotective pathways in the setting of preconditioning. We highlight the protective role of the interferon-related response and the potential site of action for TLR preconditioning involving the blood-brain-barrier. Pharmacological modulation of TLR activation to promote protection against stroke is a promising approach for the development of prophylactic and acute therapies targeting ischemic brain injury. PMID:24709682

  14. Ischemic retinopathy associated with Crohn’s disease

    PubMed Central

    Siqueira, Rubens Camargo; Kaiser Junior, Roberto Luiz; Ruiz, Lilian Piron; Ruiz, Milton Arthur

    2016-01-01

    Purpose To report a case of a patient with ischemic retinopathy associated with Crohn’s disease. Case report This report presents a case of a 28-year-old female patient with Crohn’s disease and sudden decrease of visual acuity in the right eye. Fluorescein angiography, optical coherence tomography, and multifocal electroretinography confirmed the clinical features of ischemic retinopathy. After systemic corticosteroid treatment, the patient developed epiretinal membrane without significant improvement in visual acuity. Discussion The patient presented with ischemic retinopathy associated with Crohn’s disease with deficiency of central visual acuity. Periodic examination by a retina specialist is recommended for patients being treated for Crohn’s disease. PMID:27524921

  15. Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury

    PubMed Central

    Fan, Jie; Wu, Bill X.; Crosson, Craig E.

    2016-01-01

    Purpose Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. However, the role ASMase plays in ischemic retinal injury has not been investigated. The purpose of this study was to investigate how reduced ASMase expression impacts retinal ischemic injury. Methods Changes in ceramide levels and ASMase activity were determined by high performance liquid chromatography-tandem mass spectrometry analysis and ASMase activity. Retinal function and morphology were assessed by electroretinography (ERG) and morphometric analyses. Levels of TNF-α were determined by ELISA. Activation of p38 MAP kinase was assessed by Western blot analysis. Results In wild-type mice, ischemia produced a significant increase in retinal ASMase activity and ceramide levels. These increases were associated with functional deficits as measured by ERG analysis and significant structural degeneration in most retinal layers. In ASMase+/− mice, retinal ischemia did not significantly alter ASMase activity, and the rise in ceramide levels were significantly reduced compared to levels in retinas from wild-type mice. In ASMase+/− mice, functional and morphometric analyses of ischemic eyes revealed significantly less retinal degeneration than in injured retinas from wild-type mice. The ischemia-induced increase in retinal TNF-α levels was suppressed by the administration of the ASMase inhibitor desipramine, or by reducing ASMase expression. Conclusions Our results demonstrate that reducing ASMase expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators plays a role in the development of ischemic retinal injury. Modulating ASMase may present new opportunities for adjunctive therapies when treating retinal ischemic disorders. PMID:27571014

  16. Genome wide analysis of blood pressure variability and ischemic stroke

    PubMed Central

    Khan, Muhammad S; Nalls, Michael A; Bevan, Steve; Cheng, Yu-Ching; Chen, Wei-Min; Malik, Rainer; McCarthy, Nina S; Holliday, Elizabeth G; Speed, Douglas; Hasan, Nazeeha; Pucek, Mateusz; Rinne, Paul E.; Sever, Peter; Stanton, Alice; Shields, Denis C; Maguire, Jane M; McEvoy, Mark; Scott, Rodney J; Ferrucci, Luigi; Macleod, Mary J; Attia, John; Markus, Hugh S; Sale, Michele M; Worrall, Bradford B; Mitchell, Braxton D; Dichgans, Martin; Sudlow, Cathy; Meschia, James F; Rothwell, Peter M

    2013-01-01

    Background and Purpose Visit-to-visit variability in BP is associated with ischemic stroke. We sought to determine whether such variability has a genetic aetiology and whether genetic variants associated with BP variability are also associated with ischemic stroke. Methods A GWAS for loci influencing BP variability was undertaken in 3,802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study where long-term visit-to-visit and within visit BP measures were available. Since BP variability is strongly associated with ischemic stroke, we genotyped the sentinel SNP in an independent ischemic stroke population comprising of 8,624 cases and 12,722 controls and in 3,900 additional (Scandinavian) participants from the ASCOT study in order to replicate our findings. Results The ASCOT discovery GWAS identified a cluster of 17 correlated SNPs within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (p=1.4×10−8). Conditional analysis on rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in ischemic stroke patients found no association for overall stroke (OR 1.02; 95% CI 0.97-1.07; p=0.52) or its sub-types: CE (OR 1.07; 95% CI 0.97-1.16; p=0.17), LVD (OR 0.98; 95% 0.89-1.07; p=0.60) and SVD (OR 1.07; 95% CI 0.97-1.17; p=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (p=0.18). Conclusions We identified a cluster of SNPs at the NLGN1 locus showing significant association with BP variability. Follow up analyses did not support an association with risk of ischemic stroke and its subtypes. PMID:23929743

  17. IL1RN VNTR Polymorphism in Ischemic Stroke

    PubMed Central

    Worrall, Bradford B.; Brott, Thomas G.; Brown, Robert D.; Brown, W. Mark; Rich, Stephen S.; Arepalli, Sampath; Wavrant-De Vrièze, Fabienne; Duckworth, Jaime; Singleton, Andrew B.; Hardy, John; Meschia, James F.

    2008-01-01

    Background and Purpose Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease. Methods An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. Results After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant. Conclusions Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted. PMID:17332449

  18. Biomarkers Associated with Ischemic Stroke in Diabetes Mellitus Patients.

    PubMed

    Yang, Shuisheng; Zhao, Jingfeng; Chen, Yuxiang; Lei, Minxiang

    2016-07-01

    Diabetes is an established risk factor for ischemic stroke, but the associated molecular mechanisms remain to be fully elucidated. This study investigated the role of plasma and platelet microRNAs and their targeting proteins in the activation of platelets and their association with the occurrence of ischemic stroke in patients with type 2 diabetes mellitus (T2DM). Results showed that the expressions of platelet and plasma miR-144 and miR-223 were significantly altered in T2DM patients with or without ischemic stroke compared to that in healthy controls, but these changes were more significant in T2DM patients with ischemic stroke. The expressions of P2Y12 and IRS-1 as well as phosphorylation levels of IRS-1, PI3K, and Akt in platelets were significantly altered in T2DM patients with or without ischemic stroke. The expression of platelet miR-144 and miR-223 significantly correlated with their plasma levels, P2Y12 and IRS-1 expression, blood glucose concentration, and platelet activation rate. High glucose concentration significantly elevated P-selectin, miR-144 and P2Y12 expression and significantly reduced miR-223 and IRS-1 expression in UT-7 cells. Overexpression of miR-223 and blocking of miR-144 expression significantly normalized the effects of high glucose concentration in UT-7 cells. In conclusion, hyperglycemia may activate platelets through miR-144 and miR-223 to downregulate IRS-1 and upregulate P2Y12 expression in the platelets of T2DM patients through an IRS-1-PI3K-Akt signaling. Low platelet and plasma miR-223 expression in addition to high platelet and plasma miR-144 expression are risk factors for ischemic stroke in T2DM patients. PMID:26175178

  19. LIPID LEVELS AND THE RISK OF ISCHEMIC STROKE IN WOMEN

    PubMed Central

    Kurth, Tobias; Everett, Brendan M.; Buring, Julie E.; Kase, Carlos S.; Ridker, Paul M; Gaziano, J. Michael

    2006-01-01

    Objective To evaluate the association between total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, and non-HDL-C with the risk of ischemic stroke in a large cohort of apparently healthy women. Methods Prospective cohort study among 27,937 US women aged ≥45 years participating in the Women's Health Study who provided baseline blood samples. Stroke occurrence was self-reported and confirmed by medical record review. We categorized plasma lipid measurements into quintiles. We used Cox proportional hazards models to evaluate the association between lipids and risk of ischemic stroke. Results During 11 years of follow-up, 282 ischemic strokes occurred. All lipid levels were strongly associated with increased risk of ischemic stroke in age-adjusted models. The association attenuated particularly for HDL-C after adjustment for potential confounders. For the comparison of the highest to the lowest quintile, the multivariable-adjusted hazard ratios (95% confidence intervals; P for trend across mean quintile values) of ischemic stroke were 2.27 (1.43-3.60; Ptrend<0.001) for total cholesterol; 1.74 (1.14-2.66; Ptrend=0.003) for LDL-C; 0.78 (0.52-1.17; Ptrend=0.27) for HDL-C; 1.65 (1.06-2.58; Ptrend=0.02) for total cholesterol to HDL-C ratio; and 2.45 (1.54-3.91; Ptrend<0.001) for non-HDL-C. Conclusions In this large cohort of apparently healthy women, total cholesterol, low-density lipoprotein cholesterol, the total cholesterol to high-density lipoprotein cholesterol ratio, and non-high-density lipoprotein cholesterol were significantly associated with increased risk of ischemic stroke. PMID:17310025

  20. Personalized approach to primary and secondary prevention of ischemic stroke

    PubMed Central

    2014-01-01

    Primary and secondary prevention of ischemic stroke represents a significant part of stroke management and health care. Although there are official guidelines concerning stroke management, new knowledge are introduced to them with a slight delay. This article provides an overview of current information on primary and secondary prevention of ischemic stroke. It summarizes information especially in the field of cardioembolic stroke, the use of new anticoagulants and the management of carotid stenosis based on the results of recent clinical studies. The optimal approach in stroke management is to follow these recommendations, to know new strategies and to apply an individual personalized approach in our clinical decisions. PMID:24949113

  1. Ischemic colitis after mesotherapy combined with anti-obesity medications.

    PubMed

    Kim, Jong Bin; Moon, Won; Park, Seun Ja; Park, Moo In; Kim, Kyu-Jong; Lee, Jae Nam; Kang, Seong Joo; Jang, Lee La; Chang, Hee Kyung

    2010-03-28

    Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors. PMID:20333798

  2. Factoring in Factor VIII With Acute Ischemic Stroke

    PubMed Central

    Siegler, James E.; Samai, Alyana; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl

    2016-01-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. PMID:25669199

  3. Anesthesia for Endovascular Approaches to Acute Ischemic Stroke.

    PubMed

    Avitsian, Rafi; Machado, Sandra B

    2016-09-01

    Involvement of the Anesthesiologist in the early stages of care for acute ischemic stroke patient undergoing endovascular treatment is essential. Anesthetic management includes the anesthetic technique (general anesthesia vs sedation), a matter of much debate and an area in need of well-designed prospective studies. The large numbers of confounding factors make the design of such studies a difficult process. A universally agreed point in the endovascular management of acute ischemic stroke is the importance of decreasing the time to revascularization. Hemodynamic and ventilatory management and implementation of neuroprotective modalities and treatment of acute procedural complications are important components of the anesthetic plan. PMID:27521194

  4. Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

    PubMed

    Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

    2004-01-01

    Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion. PMID:16247851

  5. New method of posterior scallop augmentation for ischemic mitral regurgitation.

    PubMed

    Aoki, Masakazu; Ito, Toshiaki

    2015-03-01

    We report a new method of posterior middle scallop (P2) augmentation for ischemic mitral regurgitation to achieve deep coaptation. First, P2 was divided straight at the center and partially detached from the annulus in a reverse T shape. A narrow pentagon-shaped section of pericardium was sutured to the divided P2 and annular defect. The tip of the pentagon was attached directly to the papillary muscle, thus creating a very large P2 scallop. A standard-sized ring was placed. We adopted this technique in 2 patients with advanced ischemic cardiomyopathy, and no mitral regurgitation was observed during a 1-year follow-up. PMID:25742844

  6. Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke.

    PubMed

    Glueck, C J; Fontaine, R N; Wang, P

    2001-02-01

    Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband's mother and brother had deep venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband's brother was heterozygous for the G20210A prothrombin gene mutation. The proband's niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband's heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogen-progestin oral contraceptives were given to the proband's niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke. PMID:11246543

  7. Remote limb ischemic conditioning enhances motor learning in healthy humans.

    PubMed

    Cherry-Allen, Kendra M; Gidday, Jeff M; Lee, Jin-Moo; Hershey, Tamara; Lang, Catherine E

    2015-06-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions. PMID:25867743

  8. [Ischemic stroke: A rare complication of liver hydatid cyst].

    PubMed

    Ghadhoune, H; Chaari, A; Baccouche, N; Chelly, H; Bouaziz, M

    2013-10-01

    Hydatid cyst of the liver (HCL) is a widespread disease in North African countries. We report the case of a 39-year-old patient who was admitted in our intensive care unit because of anaphylactic shock due to a cracked HCL fortuitously discovered. This accident was also complicated by an ischemic stroke witch underline mechanisms are discussed. PMID:24075197

  9. Brainstem ischemic stroke after to Bothrops atrox snakebite.

    PubMed

    Cañas, Carlos A

    2016-09-15

    We report case of a 48 years old woman bitten on her right foot by a Bothrops atrox viper. As a result, she developed a severe coagulopathy which improved with application of polyvalent antivenom. Four days after bite she suffered a devastating brainstem ischemic stroke. Possible pathogenetic mechanisms are discussed. PMID:27527269

  10. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  11. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke

    PubMed Central

    Piggott, Damani A.; Carroll, Karen C.; Lim, Michael; Melia, Michael T.

    2016-01-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  12. Glibenclamide for the treatment of ischemic and hemorrhagic stroke.

    PubMed

    Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. PMID:25749474

  13. [Development of Researches on Scalp Acupuncture for Ischemic Stroke].

    PubMed

    Tian, Liang; Wang, Jin-hai; Sun, Run-jie; Zhang, Xing-hua; Yuan, Bo; Du, Xiao-zheng

    2016-02-01

    Ischemic stroke is one of the commonly met diseases in clinical practice nowadays. Acupuncture therapy is widly used in the treatment of sequela of ischemic stroke in China and its mechanisms have been extensively studied in recen years. In the present paper, the authors focus on the development of studies on the mechanism of scalp acupuncture therapy in the treatment of ischemic stroke. Results indicate that scalp acupuncture intervention can 1) improve cerebral blood circulation to promote regional energy metabolism, 2) up-regulate expression of glial cell-line derived neurotrophic factor (GDNF), etc., possibly promoting proliferation and differentiation of neural stem cells in the focal cerebral cortex and hippocampus, 3) reduce contents of excitatory amino acid and increase level of gamma-aminobutyric acid (GABA) to lower neurogenic toxicity, and relieve cerebral injury, 4) ease cerebral vascular immunoinflammatory reactions, 5) regulate blood lipid metabolism to resist cerebral free radical damage, and 6) inhibit cerebral cortical apoptosis. However, these results only revealed very limited intrinsic mechanisms of scalp acupuncture in improving ischemic stroke. Further studies using comprehensive techniques of multi-disciplines as molecular biology, electrophysiology, etc. are definitely needed. PMID:27141629

  14. [Ischemic stroke as reaction to an acute stressful event].

    PubMed

    Ibrahimagić, Omer C; Sinanović, Osman; Cickusić, Amra; Smajlović, Dzevdet

    2005-01-01

    The period following ischemic stroke can be considered as a reaction to a stressful event. Changes in cortisol secretion are one of the indicators of stress reaction. The aim of the study was to determine morning serum levels of cortisol in stroke patients within 48 hours and 15 days of ischemic stroke onset. Study group included 40 patients, 20 of them were females, mean age 65.3 +/- 10.3 years. The patients did not receive any corticosteroid agents or spironolactone, and did not suffer from Cushing's or Addison's syndrome. Ischemic stroke was verified by computed tomography of the brain. The fluorometric method with DELFIA Cortisol immunoassay was used to determine morning serum cortisol levels. Reference values of the measured hormone were 201-681 nmol/l. The mean level of serum cortisol within 48 hours of stroke was 560.9 +/- 318.9 nmol/l, and on day 15 it was 426.2 +/- 159.3 nmol/l, i.e. significantly lower (p < 0.02). On the first measurement, the level of serum cortisol was elevated in 32%, and on the second measurement in only 7.5% patients, which was also significantly lower (p < 0.001). It was concluded that the stress reaction in ischemic stroke patients was more pronounced within the first 48 hours of stroke onset. Judging from the morning cortisol levels, the reaction to stress was considerably less pronounced 15 days after stroke onset. PMID:15875466

  15. The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke.

    PubMed

    Chang, Jason J; Stanfill, Ansley; Pourmotabbed, Tayebeh

    2016-01-01

    Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins. PMID:27529234

  16. Update on the Role of Cannabinoid Receptors after Ischemic Stroke

    PubMed Central

    Capettini, Luciano S. A.; Savergnini, Silvia Q.; da Silva, Rafaela F.; Stergiopulos, Nikos; Santos, Robson A. S.; Mach, François; Montecucco, Fabrizio

    2012-01-01

    Cannabinoids are considered as key mediators in the pathophysiology of inflammatory diseases, including atherosclerosis. In particular, they have been shown to reduce the ischemic injury after acute cardiovascular events, such as acute myocardial infarction and ischemic stroke. These protective and anti-inflammatory properties on peripheral tissues and circulating inflammatory have been demonstrated to involve their binding with both selective cannabinoid type 1 (CB1) and type 2 (CB2) transmembrane receptors. On the other hands, the recent discoveries of novel different classes of cannabinoids and receptors have increased the complexity of this system in atherosclerosis. Although only preliminary data have been reported on the activities of novel cannabinoid receptors, several studies have already investigated the role of CB1 and CB2 receptors in ischemic stroke. While CB1 receptor activation has been shown to directly reduce atherosclerotic plaque inflammation, controversial data have been shown on neurotransmission and neuroprotection after stroke. Given its potent anti-inflammatory activities on circulating leukocytes, the CB2 activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke. PMID:22577257

  17. Medications Used in the Treatment of Ischemic Heart Disease.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on medications used in the treatment of ischemic heart disease is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first.…

  18. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  19. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke.

    PubMed

    Piggott, Damani A; Carroll, Karen C; Lim, Michael; Melia, Michael T

    2016-04-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  20. Association of integrin α2 gene variants with ischemic stroke

    PubMed Central

    Matarin, Mar; Brown, W Mark; Hardy, John A; Rich, Stephen S; Singleton, Andrew B; Brown, Robert D; Brott, Thomas G; Worrall, Bradford B; Meschia, James F

    2008-01-01

    Genetic variants in the gene encoding integrin α2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P = 0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P= 0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes. PMID:17534386

  1. The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke

    PubMed Central

    Chang, Jason J.; Stanfill, Ansley; Pourmotabbed, Tayebeh

    2016-01-01

    Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins. PMID:27529234

  2. The effects of citicoline on acute ischemic stroke: a review.

    PubMed

    Overgaard, Karsten

    2014-08-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit. PMID:24739589

  3. Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism

    PubMed Central

    Bir, Shyamal C.; Pattillo, Christopher B.; Pardue, Sibile; Kolluru, Gopi K.; Docherty, John; Goyette, Dave; Dvorsky, Peter

    2012-01-01

    Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and as such therapies augmenting its bioavailability may be useful for the treatment of ischemic tissue diseases. Here we examine the effect of administering the NO prodrug sodium nitrite on arteriogenesis activity during established tissue ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral artery and vein ligation. Five days postligation; animals were randomized to control PBS or sodium nitrite (165 μg/kg) therapy twice daily. In situ vascular remodeling was measured longitudinally using SPY angiography and Microfil vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb arterial vessel diameter and branching in a NO-dependent manner. SPY imaging angiography over time showed that nitrite therapy enhanced ischemic gracillis collateral vessel formation from the profunda femoris to the saphenous artery. Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug sodium nitrite significantly increases arteriogenesis and reperfusion of established severe chronic tissue ischemia. PMID:22610173

  4. The neuroprotective roles of BDNF in hypoxic ischemic brain injury.

    PubMed

    Chen, Ai; Xiong, Li-Jing; Tong, Yu; Mao, Meng

    2013-03-01

    Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury. PMID:24648914

  5. Therapy Effects of Bone Marrow Stromal Cells on Ischemic Stroke

    PubMed Central

    Ye, Xinchun; Hu, Jinxia; Cui, Guiyun

    2016-01-01

    Stroke is the second most common cause of death and major cause of disability worldwide. Recently, bone marrow stromal cells (BMSCs) have been shown to improve functional outcome after stroke. In this review, we will focus on the protective effects of BMSCs on ischemic brain and the relative molecular mechanisms underlying the protective effects of BMSCs on stroke. PMID:27069533

  6. Risk factors and outcomes of childhood ischemic stroke in Taiwan.

    PubMed

    Lee, Ying-Ying; Lin, Kuang-Lin; Wang, Huei-Shyong; Chou, Min-Liang; Hung, Po-Cheng; Hsieh, Meng-Ying; Lin, Jainn-Jim; Wong, Alex Mun-Ching

    2008-01-01

    In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke. PMID:17573220

  7. Martorell hypertensive ischemic leg ulcer: an underdiagnosed Entity©.

    PubMed

    Alavi, Afsaneh; Mayer, Dieter; Hafner, Jürg; Sibbald, R Gary

    2012-12-01

    Martorell hypertensive ischemic leg ulcer represents rapidly progressive and extremely painful ulcers that are frequently underdiagnosed. These occur most commonly on the lateral-dorsal calf and are associated with hypertension and diabetes. This article will synthesize a review of the literature for the accurate diagnosis and treatment of this painful debilitating condition. PMID:23151767

  8. Remote limb ischemic conditioning enhances motor learning in healthy humans

    PubMed Central

    Cherry-Allen, Kendra M.; Gidday, Jeff M.; Lee, Jin-Moo; Hershey, Tamara

    2015-01-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions. PMID:25867743

  9. [Ischemic insult in the anterior and posterior cerebral circulation].

    PubMed

    Smajlović, Dzevdet; Ibrahimagić, Omer; Dostović, Zikrija

    2003-01-01

    In the everyday practice among clinical and etiological classifications for ischemic stroke, the terms strokes in the anterior and posterior cerebral circulation are also in use. The aim of this study was to analyze the frequency of ischemic strokes in the anterior and posterior circulation, their age and sex distribution, risk factors and hospital mortality. In the study it was analyzed 1772 patients with acute ischemic stroke hospitalized at the Department of Neurology Tuzla, Bosnia and Herzegovina, between January 1st 1996 and December 31st 2000. The mean age was 65.5 years (+9.9), 942 (55%) were females. Ischemic strokes for all patients were confirmed with computed tomography, while other data were collected from the standard patients' history charts. Anterior circulation stroke (ACS) had 1408 patients (81.8%), the rest of 314 (18.2%) had posterior circulation stroke (PCS). In the both types females were slightly overrepresented: 784 (56%) in ACS, and 158 (50.5%) in PCS. Moreover, females were significantly older than males: 67 (+9.8) versus 64 (+10) years in ACS (p < 0.001), 67.5 (+10.3) versus 63.5 (+9.2) in PCS (p < 0.001). Hypertension was the major risk factor occurring in 67% patients with ACS and 71 with PCS; heart diseases 54% in the both types, and diabetes in 23% patients with ACS and 20% with PCS. The cortical ischemic lesion was verified in 46% patients with ACS, 41% with PCS; subcortical in 12.5% and 14.5%; and lacunar in 41.5% and 44.5%, respectively. Hospital mortality was 30% (430 patients) for ACS, and 32% (101 patients) for PCS. Hospital mortality was considerably higher among females: 33% versus 28% for ACS (p = 0.03), 38% versus 27% for PCS (p = 0.03). On the basis of our study we can conclude that ischemic strokes in the anterior cerebral circulation are 4/5 of all ischemic strokes at the Department of Neurology Tuzla. Both, anterior and posterior circulation strokes are more frequent in females, witches were in average older than males

  10. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells.

    PubMed

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  11. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells

    PubMed Central

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  12. Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia- reperfusion injury★

    PubMed Central

    Zhang, Ying; Liu, Xiangrong; Yan, Feng; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2012-01-01

    Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury. PMID:25745448

  13. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury

    PubMed Central

    White, Laura E.; Santora, Rachel J.; Cui, Yan; Moore, Frederick A.

    2012-01-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1−/− mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets. PMID:22728466

  14. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    SciTech Connect

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-12-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  15. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.

    2009-01-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  16. Hemodilution increases cerebral blood flow in acute ischemic stroke

    SciTech Connect

    Vorstrup, S.; Andersen, A.; Juhler, M.; Brun, B.; Boysen, G.

    1989-07-01

    We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc of dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.

  17. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601

  18. Ischemic Preconditioning in White Matter: Magnitude and Mechanism

    PubMed Central

    Hamner, Margaret A.; Ye, Zucheng; Lee, Richard V.; Colman, Jamie R.; Le, Thu; Gong, Davin C.; Weinstein, Jonathan R.

    2015-01-01

    Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon whereby brief ischemic exposure confers tolerance to a subsequent ischemic challenge. IPC has not been studied selectively in CNS white matter (WM), although stroke frequently involves WM. We determined whether IPC is present in WM and, if so, its mechanism. We delivered a brief in vivo preconditioning ischemic insult (unilateral common carotid artery ligation) to 12- to 14-week-old mice and determined WM ischemic vulnerability [oxygen–glucose deprivation (OGD)] 72 h later, using acutely isolated optic nerves (CNS WM tracts) from the preconditioned (ipsilateral) and control (contralateral) hemispheres. Functional and structural recovery was assessed by quantitative measurement of compound action potentials (CAPs) and immunofluorescent microscopy. Preconditioned mouse optic nerves (MONs) showed better functional recovery after OGD than the non-preconditioned MONs (31 ± 3 vs 17 ± 3% normalized CAP area, p < 0.01). Preconditioned MONs also showed improved axon integrity and reduced oligodendrocyte injury compared with non-preconditioned MONs. Toll-like receptor-4 (TLR4) and type 1 interferon receptor (IFNAR1), key receptors in innate immune response, are implicated in gray matter preconditioning. Strikingly, IPC-mediated WM protection was abolished in both TLR4−/− and IFNAR1−/− mice. In addition, IPC-mediated protection in WM was also abolished in IFNAR1fl/fl LysMcre, but not in IFNAR1fl/fl control, mice. These findings demonstrated for the first time that IPC was robust in WM, the phenomenon being intrinsic to WM itself. Furthermore, WM IPC was dependent on innate immune cell signaling pathways. Finally, these data demonstrated that microglial-specific expression of IFNAR1 plays an indispensable role in WM IPC. SIGNIFICANCE STATEMENT Ischemic preconditioning (IPC) has been studied predominantly in gray matter, but stroke in humans frequently involves white matter (WM) as well. Here we

  19. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  20. Ischemic retinopathy and neovascular proliferation secondary to severe head injury.

    PubMed

    Coban-Karatas, Muge; Altan-Yaycioglu, Rana

    2014-01-01

    We report a case with severe head trauma and perforating globe injury in one eye and ischemic retinopathy and neovascular proliferation in the other eye. A 37-year-old male was brought to the emergency department after a motor vehicle accident with severe maxillofacial trauma. Ophthalmic examination revealed hematoma of the left eyelids as well as traumatic rupture and disorganization of the left globe. On the right eye, anterior segment and fundoscopic examination were normal. Primary globe repair was performed. At postoperative one-month visit, the right eye revealed no pathology of the optic disc and macula but severe neovascularization in the temporal peripheral retina. The patient was diagnosed as ischemic retinopathy and neovascular proliferation due to head trauma. PMID:25143848

  1. Melatonin and Ischemic Stroke: Mechanistic Roles and Action

    PubMed Central

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2015-01-01

    Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. PMID:26435711

  2. Drug repurposing for immune modulation in acute ischemic stroke.

    PubMed

    Amantea, Diana; Bagetta, Giacinto

    2016-02-01

    Innate immune cells play a dualistic role in the evolution of ischemic brain damage, with classic phenotypes promoting injury, and alternatively activated M2 microglia/macrophages or N2 neutrophils providing tissue remodelling and repair. Recently, a number of drugs commonly used for other indications (i.e., azithromycin, minocycline, bexarotene, rosiglitazone, metformin) was reported to provide neuroprotection in preclinical stroke models by promoting immune polarization towards non-inflammatory, protective phenotypes. Repurposing drugs with a well-established safety profile should allow a reduction in the risk of clinical trial failure that has dominated the unsuccessful development of neuroprotective drugs in stroke during the last decades. The clinical validation of the proof of concept, followed by the assessment of safety and efficacy of immune-polarizing repurposed drugs will definitively offer new opportunities for the acute treatment of ischemic stroke. PMID:26657075

  3. Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry

    PubMed Central

    Wang, Wei Zhong

    2008-01-01

    Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery. PMID:18946882

  4. The Siblings With Ischemic Stroke Study (SWISS): A Progress Report

    PubMed Central

    Meschia, James F.; Kissela, Brett M.; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Beck, Jeanne; Skarp, Alexa N.

    2006-01-01

    There is increasing evidence that genetic factors are associated with ischemic stroke, including multiple recent reports of association with the gene PDE4D, encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are important but can be logistically difficult to perform. This article reviews the design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems in performing a sibling-based pedigree study where proband-initiated consent is used to enroll pedigree members. Proband-initiated enrollment optimizes privacy protections for family members, but it is associated with a substantial pedigree non-completion rate such that 3 to 4 probands must be identified to obtain one completed sibling pedigree. This report updates the progress of enrollment in the SWISS protocol, discusses barriers to pedigree completion and describes innovative approaches used by the SWISS investigators to enhance enrollment. PMID:16595789

  5. Acute vertebrobasilar ischemic stroke due to electric injury.

    PubMed

    Singh Jain, Rajendra; Kumar, Sunil; Suresh, Desai Tushar; Agarwal, Rakesh

    2015-07-01

    Electrical injuries are most commonly due to household accidents.Various factors determine the severity of electric injury, including type of current, amperage, voltage, tissue resistance, pathway of current,and duration of contact with the body. Various types of neurologic damage due to electrical injury have been described in literature. It may manifest as peripheral nerve injury, spinal cord damage, seizures, cerebellarataxia, hypoxic encephalopathy, and intracerebral hemorrhage. Acute ischemic stroke is an infrequent complication of electrical injury. Herein,we report a case of middle-aged man, who accidentally sustained high voltage electrical injury followed by acute vertebrobasilar ischemic stroke. Magnetic resonance imaging of the brain showed acute infarctin bilateral cerebellar and medial occipital regions. Computed tomographic angiogram of the brain and neck vessels was normal. Possibly,in our patient, the mechanism could be related to direct vascular injury due to electric current. PMID:25684743

  6. Optical-resolution photoacoustic microscopy of ischemic stroke

    NASA Astrophysics Data System (ADS)

    Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

    2011-03-01

    A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

  7. [The Oradea study regarding the epidemiology factors in ischemic cardiopathy].

    PubMed

    Pop, E; Popa, I; Bolcaş, D; Sirca, D; Simon, F; Costin, V; Balaj, V; Micle, T; Săvulescu, I H; Elenes, S; Negru, M; Cazacu, G; Popper, A; Gerhardt, L; Zavornic, E; Anton, N; Erdös, I; Frăţilă, H; Nica, V; Mesaroş, P; Jozsa, P; Lupu, D; David, D; Derecskey, E; Man, C; Palfi, E; Vass, H L

    1981-01-01

    Cholesterolemia in a population of 100482 inhabitants of the Bihor district, subjected to screening for the risk factors in ischemic cardiopathy were studied. Together with hyperlipidemias other risk factors were detected: arterial hypertension, obesity, diabetes mellitus, smoking, ischemic alterations of the electrocardiogram, the influence of the noxious agents present at the working place, of the blood groups and disturbances of the menstrual cycle. The mean cholesteremia is of 205 ± 43.7 mgr% (M = 207 ± 43.7 mgr%; F = 204 ± 43.5 mgr%). The prevalence of cholesterolemia, in comparison with the higher normal limits in each age group over 15 years of age, is in the entire studied series, of 13.5%. The population in whom cholesterolemia exceeds 250 mgr% represents 13.92%. PMID:25528799

  8. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    PubMed Central

    Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C–associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention. PMID:23543984

  9. [Multimodal imaging of ischemic heart diseases: A 2015 update].

    PubMed

    Di Marco, L; Rosset, M; Zhang-Yin, J; Ohana, M

    2016-05-01

    Current realities and future possibilities of imaging in the ischemic heart diseases are very broad and constantly evolving, with the improvement of existing technologies and the introduction of new features such as dual-energy CT, strain ultrasound, multimodality fusion or perfusion MRI. Regular collaboration between prescribing clinicians, cardiologists, radiologists and nuclear radiologists is therefore essential to tailor the examination to the specific clinical question. The indications for each modality will therefore depend on its diagnostic performance, cost, acquisition and post-processing times and eventual radiation exposure. This review will detail principles and applications of current cardiac imaging examinations: echocardiography, nuclear medicine, MRI, CT and coronary angiography, emphasizing their current strengths and weaknesses in the ischemic heart diseases management. PMID:26775644

  10. Review of current and emerging therapies in acute ischemic stroke.

    PubMed

    Novakovic, R; Toth, G; Purdy, P D

    2009-07-01

    The statistics for stroke in the USA reads like a familiar ad slogan cited in most papers pertaining to acute ischemic stroke (AIS). Stroke is the third leading cause of death in the USA. While stroke ranks third among all causes of death, behind diseases of the heart and cancer, it is the leading cause of serious long-term disability in the USA.(1) Approximately 795 000 people, 87% of whom are ischemic, suffer from stroke each year in the USA.(2) That means that on average, every 40 seconds someone within the USA develops a stroke. For 2009 the combined direct and indirect cost of stroke, from hospitalization and rehabilitation to institutionalization, is estimated at $68.9 billion within the USA.(2). PMID:21994100

  11. Nanoparticles-Assisted Stem Cell Therapy for Ischemic Heart Disease

    PubMed Central

    Zhu, Kai; Li, Jun; Wang, Yulin; Lai, Hao; Wang, Chunsheng

    2016-01-01

    Stem cell therapy has attracted increasing attention as a promising treatment strategy for cardiac repair in ischemic heart disease. Nanoparticles (NPs), with their superior physical and chemical properties, have been widely utilized to assist stem cell therapy. With the help of NPs, stem cells can be genetically engineered for enhanced paracrine profile. To further understand the fate and behaviors of stem cells in ischemic myocardium, imaging NPs can label stem cells and be tracked in vivo under multiple modalities. Besides that, NPs can also be used to enhance stem cell retention in myocardium. These facts have raised efforts on the development of more intelligent and multifunctional NPs for cellular application. Herein, an overview of the applications of NPs-assisted stem cell therapy is given. Key issues and future prospects are also critically addressed. PMID:26839552

  12. Brain imaging in transient ischemic attack--redefining TIA.

    PubMed

    Pavlovic, Aleksandra M; Barras, Christen D; Hand, Peter J; Tress, Brian M; Desmond, Patricia M; Davis, Stephen M

    2010-09-01

    Transient ischemic attack (TIA) has recently been redefined to incorporate the latest clinical and neuroimaging information that has shed new light on TIA pathophysiology. Patients suffering from TIA are at a substantial risk of subsequent stroke, but quantifying this risk is difficult as TIA patients are a heterogeneous population and there are multiple TIA mimics. Clinical scores for prediction of stroke risk are principally based on patient history and potentially understate actual risk. Magnetic resonance imaging (MRI), in particular diffusion-weighted imaging (DWI) performed in the first days following TIA, reveals relevant focal ischemic abnormalities in 21-68% of patients. These lesions predict stroke recurrence, functional dependence and subsequent vascular events. Adding imaging information to clinical scores improves prediction of stroke risk following TIA. Alongside clinical judgement, use of MRI has the potential to change the management of TIA patients and is the imaging modality of choice for this condition. PMID:20605469

  13. Antisense oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury.

    PubMed

    Nakamura, Kenji; Kadotani, Yayoi; Ushigome, Hidetaka; Akioka, Kiyokazu; Okamoto, Masahiko; Ohmori, Yoshihiro; Yaoi, Takeshi; Fushiki, Shinji; Yoshimura, Rikio; Yoshimura, Norio

    2002-09-27

    Tissue factor (TF) is an initiation factor for blood coagulation and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury. AS-1/TF was delivered intravenously to Lewis rats. After 10 h, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 min and harvested. TF expression was studied using immunohistochemical staining. One of 10 rats survived in a 5-day survival rate and TF was strongly stained on endothelial cells in non-treatment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells. These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver. PMID:12270110

  14. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke. PMID:27071728

  15. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

    PubMed Central

    Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds. PMID:27028201

  16. Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study

    PubMed Central

    Maier, Oskar; Schröder, Christoph; Forkert, Nils Daniel; Martinetz, Thomas; Handels, Heinz

    2015-01-01

    Motivation Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. Methods In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. Results and Conclusion The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID:26672989

  17. Delayed Postconditioning Protects against Focal Ischemic Brain Injury in Rats

    PubMed Central

    Ren, Chuancheng; Gao, Xuwen; Niu, Gang; Yan, Zhimin; Chen, Xiaoyuan; Zhao, Heng

    2008-01-01

    Background We and others have reported that rapid ischemic postconditioning, interrupting early reperfusion after stroke, reduces infarction in rats. However, its extremely short therapeutic time windows, from a few seconds to minutes after reperfusion, may hinder its clinical translation. Thus, in this study we explored if delayed postconditioning, which is conducted a few hours after reperfusion, offers protection against stroke. Methods and Results Focal ischemia was generated by 30 min occlusion of bilateral common carotid artery (CCA) combined with permanent occlusion of middle cerebral artery (MCA); delayed postconditioning was performed by repetitive, brief occlusion and release of the bilateral CCAs, or of the ipsilateral CCA alone. As a result, delayed postconditioning performed at 3h and 6h after stroke robustly reduced infarct size, with the strongest protection achieved by delayed postconditioning with 6 cycles of 15 min occlusion/15 min release of the ipsilateral CCA executed from 6h. We found that this delayed postconditioning provided long-term protection for up to two months by reducing infarction and improving outcomes of the behavioral tests; it also attenuated reduction in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-uptake therefore improving metabolism, and reduced edema and blood brain barrier leakage. Reperfusion in ischemic stroke patients is usually achieved by tissue plasminogen activator (tPA) application, however, t-PA's side effect may worsen ischemic injury. Thus, we tested whether delayed postconditioning counteracts the exacerbating effect of t-PA. The results showed that delayed postconditioning mitigated the worsening effect of t-PA on infarction. Conclusion Delayed postconditioning reduced ischemic injury after focal ischemia, which opens a new research avenue for stroke therapy and its underlying protective mechanisms. PMID:19066627

  18. Heat shock response for ischemic kidney preservation and transplantation.

    PubMed

    Kaneko, H; Perdrizet, G A; Schweizer, R T

    1993-01-01

    The heat shock response (HSR) is a form of stress conditioning during which reversible changes in cellular metabolism are rapidly induced by brief exposure to supra-physiologic levels of heat. The nature of these adaptive adjustments has been widely investigated and has received much attention in molecular biology and cancer research. Recent evidence indicates that a basic form of this stress response exists at the cellular level of virtually every organism. Although the physiological phenomenon of HSR is complex, it is well known that it can induce specific proteins, known as heat shock proteins (HSP's), which are not normally synthesized. HSP's become the major proteins synthesized during the heat shock response while normal protein synthesis is suppressed. In addition, the HSR has been demonstrated to confer a transient resistance to the organism to subsequent episodes of stress. Recently it has been reported that the HSR confers protection against cold ischemic injury and extends the cold preservation time of the rat kidney to 48 hours. In this study, we have applied the concept of HSR to the preservation, and transplantation of warm ischemically injured pig kidneys. Since there is a serious shortage of cadaver kidneys available for transplantation worldwide, this number would increase if warm ischemic kidneys could be utilized. However with present methods of organ recovery and preservation, such kidneys are not likely to function after transplantation even if they were removed. We hypothesized that the application of a thermal stress to pig kidneys prior to organ procurement and preservation will enhance the organs' ability to function after warm ischemic injury. PMID:8352637

  19. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities. PMID:21445508

  20. Angiogenesis-regulating microRNAs and ischemic stroke

    PubMed Central

    Yin, Ke-Jie; Hamblin, Milton; Chen, Y. Eugene

    2014-01-01

    Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID:26156265

  1. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    PubMed Central

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  2. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing. PMID:25102201

  3. Correlation Analysis of Sleep Quality and Youth Ischemic Stroke

    PubMed Central

    Zhang, Shunqing; Chang, Cheng; Zhang, Juan; Song, Bo; Fang, Hui; Xu, YuMing

    2014-01-01

    Objective. To study risk factors related to ischemic stroke (IS) in youth and the influence of sleep quality on youth ischemic stroke incidence. Methods. 223 patients aged 18 to 45 years who were admitted to Puyang People's Hospital from June 2011 to February 2013 with a first-ever ischemic stroke were selected as the research cases. 158 young people with a normal physical examination were selected as the control group. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to analyse the correlation between sleep quality and youth IS incidence. The US National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (MRS) scores were used to assess cases' state of illness and prognosis three months after IS. Results. Univariate and multivariate logistic regression analysis showed that the association of these risk factors with youth IS incidence, from highest to lowest, was hypertension, hyperlipidaemia, smoking history, high homocysteine, the quality of sleep, family history of stroke, and alcoholism. Poor sleep quality ranked fifth among all risk factors and was positively correlated with poor prognosis for youth IS patients. Conclusion. The results of this study showed that sleep quality is an important factor in the pathogenesis and prognosis of youth IS. PMID:25161340

  4. Curcumin protects against ischemic spinal cord injury: The pathway effect.

    PubMed

    Zhang, Jinhua; Wei, Hao; Lin, Meimei; Chen, Chunmei; Wang, Chunhua; Liu, Maobai

    2013-12-25

    Inducible nitric oxide synthase and N-methyl-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin. Reverse transcription-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tarlov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyl-D-aspartate receptor expression. PMID:25206661

  5. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  6. Developing digital tissue phantoms for hyperspectral imaging of ischemic wounds.

    PubMed

    Xu, Ronald X; Allen, David W; Huang, Jiwei; Gnyawali, Surya; Melvin, James; Elgharably, Haytham; Gordillo, Gayle; Huang, Kun; Bergdall, Valerie; Litorja, Maritoni; Rice, Joseph P; Hwang, Jeeseong; Sen, Chandan K

    2012-06-01

    Hyperspectral imaging has the potential to achieve high spatial resolution and high functional sensitivity for non-invasive assessment of tissue oxygenation. However, clinical acceptance of hyperspectral imaging in ischemic wound assessment is hampered by its poor reproducibility, low accuracy, and misinterpreted biology. These limitations are partially caused by the lack of a traceable calibration standard. We proposed a digital tissue phantom (DTP) platform for quantitative calibration and performance evaluation of spectral wound imaging devices. The technical feasibility of such a DTP platform was demonstrated by both in vitro and in vivo experiments. The in vitro DTPs were developed based on a liquid blood phantom model. The in vivo DTPs were developed based on a porcine ischemic skin flap model. The DTPs were projected by a Hyperspectral Image Projector (HIP) with high fidelity. A wide-gap 2nd derivative oxygenation algorithm was developed to reconstruct tissue functional parameters from hyperspectral measurements. In this study, we have demonstrated not only the technical feasibility of using DTPs for quantitative calibration, evaluation, and optimization of spectral imaging devices but also its potential for ischemic wound assessment in clinical practice. PMID:22741088

  7. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  8. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

    PubMed Central

    Ikenoue, Tsuyomu

    2013-01-01

    Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult. PMID:23533962

  9. Risk factors for perioperative ischemic stroke in cardiac surgery

    PubMed Central

    da Costa, Mário Augusto Cray; Gauer, Maria Fernanda; Gomes, Ricardo Zaneti; Schafranski, Marcelo Derbli

    2015-01-01

    Objective The purpose of this study was to evaluate the risk factors for ischemic stroke in patients undergoing cardiac surgery. Methods From January 2010 to December 2012, 519 consecutive patients undergoing cardiac surgery were analyzed prospectively. The sample was divided into two groups: patients with stroke per and postoperative were allocated in Group GS (n=22) and the other patients in the group CCONTROL (n=497). The following variables were compared between the groups: gender, age, carotid stenosis ≥ 70%, diabetes on insulin, chronic obstructive pulmonary disease, peripheral arteriopathy, unstable angina, kidney function, left ventricular function, acute myocardial infarction, pulmonary arterial hypertension, use of cardiopulmonary bypass. Ischemic stroke was defined as symptoms lasting over 24 hours associated with changes in brain computed tomography scan. The variables were compared using Fisher’s exact test, Chi square, Student’s t-test and logistic regression. Results Stroke occurred in 4.2% of patients and the risk factors statistically significant were: carotid stenosis of 70% or more (P=0.03; OR 5.07; IC 95%: 1.35 to 19.02), diabetes on insulin (P=0.04; OR 2.61; IC 95%: 1.10 to 6.21) and peripheral arteriopathy (P=0.03; OR 2.61; 95% CI: 1.08 to 6.28). Conclusion Risk factors for ischemic stroke were carotid stenosis of 70% or more, diabetes on insulin and peripheral arteriopathy. PMID:26313728

  10. Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats

    PubMed Central

    Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong

    2014-01-01

    Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. PMID:24582784

  11. Ginsenoside Rd and ischemic stroke; a short review of literatures☆

    PubMed Central

    Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad

    2015-01-01

    Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821

  12. Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Chou, Ping Song; Lin, Chien Hung; Chao, Hai Lun; Chao, A Ching

    2012-11-01

    Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. PMID:22205004

  13. Do energy drinks cause epileptic seizure and ischemic stroke?

    PubMed

    Dikici, Suber; Saritas, Ayhan; Besir, Fahri Halit; Tasci, Ahmet Hakan; Kandis, Hayati

    2013-01-01

    Energy drinks are popular among young individuals and marketed to college students, athletes, and active individuals between the ages of 21 and 35 years. We report a case that had ischemic stroke and epileptic seizure after intake of energy drink with alcohol. To the best of our knowledge, the following case is the first report of ischemic stroke after intake of energy drink. A previously healthy 37-year-old man was brought to the emergency department after a witnessed tonic-clonic seizure. According to his wife's testimony, just before loss of consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull, Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a history of seizures, head trauma, or family history of seizures or another disease. In cranial diffusion magnetic resonance imaging, there were hyperintense signal changes in bilateral occipital area (more pronounced in the left occipital lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests associated with possible etiologic causes of ischemic stroke in young patients were negative. Herein, we want to attract attention to adverse effect of energy drink usage. PMID:22867827

  14. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

    PubMed Central

    Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

    2010-01-01

    Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

  15. Dual targeted nanocarrier for brain ischemic stroke treatment.

    PubMed

    Zhao, Yue; Jiang, Yan; Lv, Wei; Wang, Zhongyuan; Lv, Lingyan; Wang, Baoyan; Liu, Xin; Liu, Yang; Hu, Quanyin; Sun, Wujin; Xu, Qunwei; Xin, Hongliang; Gu, Zhen

    2016-07-10

    Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment. PMID:27142584

  16. Extracorporeal shock wave therapy for ischemic cardiovascular disorders.

    PubMed

    Ito, Kenta; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

    2011-10-01

    Ischemic heart disease is the leading cause of death and a major cause of hospital admissions, with the number of affected patients increasing worldwide. The current management of ischemic heart disease has three major therapeutic options: medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, the prognosis for patients with severe ischemic heart disease without indications for PCI or CABG still remains poor due to the lack of effective treatments. It is therefore crucial to develop alternative therapeutic strategies for severe ischemic heart disease. Extracorporeal shock wave (SW) therapy was introduced clinically more than 20 years ago to fragment kidney stones, which has markedly improved the treatment of urolithiasis. We found that a low-energy SW (about 10% of the energy density used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we initiated in vivo studies and have demonstrated that extracorporeal cardiac SW therapy with a low-energy SW up-regulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia, without any adverse effects in vivo. On the basis of promising results in animal studies, we performed a series of clinical studies in patients with severe coronary artery disease without indication for PCI or CABG, including, firstly, an open trial followed by a placebo-controlled, double-blind study. In both studies, our extracorporeal cardiac SW therapy improved symptoms, exercise capacity, and myocardial perfusion in patients with severe coronary artery disease. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction (MI) in pigs and in enhancing angiogenesis in hind-limb ischemia in

  17. NEUROPROTECTION FOR ISCHEMIC STROKE: PAST, PRESENT AND FUTURE

    PubMed Central

    Ginsberg, Myron D.

    2008-01-01

    Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safety-feasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4–6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of “failed” trials. This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany

  18. Ischemic Compression After Trigger Point Injection Affect the Treatment of Myofascial Trigger Points

    PubMed Central

    Kim, Soo A; Oh, Ki Young; Choi, Won Hyuck

    2013-01-01

    Objective To investigate the effects of trigger point injection with or without ischemic compression in treatment of myofascial trigger points in the upper trapezius muscle. Methods Sixty patients with active myofascial trigger points in upper trapezius muscle were randomly divided into three groups: group 1 (n=20) received only trigger point injections, group 2 (n=20) received trigger point injections with 30 seconds of ischemic compression, and group 3 (n=20) received trigger point injections with 60 seconds of ischemic compression. The visual analogue scale, pressure pain threshold, and range of motion of the neck were assessed before treatment, immediately after treatment, and 1 week after treatment. Korean Neck Disability Indexes were assessed before treatment and 1 week after treatment. Results We found a significant improvement in all assessment parameters (p<0.05) in all groups. But, receiving trigger point injections with ischemic compression group showed significant improvement as compared with the receiving only trigger point injections group. And no significant differences between receiving 30 seconds of ischemic compression group and 60 seconds of ischemic compression group. Conclusion This study demonstrated the effectiveness of ischemic compression for myofascial trigger point. Trigger point injections combined with ischemic compression shows better effects on treatment of myofascial trigger points in the upper trapezius muscle than the only trigger point injections therapy. But the duration of ischemic compression did not affect treatment of myofascial trigger point. PMID:24020035

  19. Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.

    PubMed

    Li, Xiao-Xia; Guan, Hong-Jun; Liu, Jian-Ping; Guo, Yu-Peng; Yang, Yong; Niu, Ying-Ying; Yao, Li-Yan; Yang, Yin-Dong; Yue, Hong-Yu; Meng, Li-Li; Cui, Xin-Yu; Yang, Xiao-Wei; Gao, Jin-Xiao

    2015-03-01

    Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P < 0.05). We found a significant association with increased ischemic stroke risk in women carrying the CC genotype of rs4965814 [hazard ratio: 2.43(1.03-5.75)]; a similar trend was also found in men carrying the TC genotype of rs4965814 [hazard ratio: 1.81(1.06-3.08)]. SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke. Understanding the inflammatory mechanisms of ischemic stroke may give new therapeutic targets to pharmacologists. PMID:25390504

  20. Effect of Extended CT Perfusion Acquisition Time on Ischemic Core and Penumbra Volume Estimation in Patients with Acute Ischemic Stroke due to a Large Vessel Occlusion

    PubMed Central

    Borst, Jordi; Marquering, Henk A.; Beenen, Ludo F. M.; Berkhemer, Olvert A.; Dankbaar, Jan Willem; Riordan, Alan J.; Majoie, Charles B. L. M.

    2015-01-01

    Background and Purpose It has been suggested that CT Perfusion acquisition times <60 seconds are too short to capture the complete in and out-wash of contrast in the tissue, resulting in incomplete time attenuation curves. Yet, these short acquisitions times are not uncommon in clinical practice. The purpose of this study was to investigate the occurrence of time attenuation curve truncation in 48 seconds CT Perfusion acquisition and to quantify its effect on ischemic core and penumbra estimation in patients with acute ischemic stroke due to a proximal intracranial arterial occlusion of the anterior circulation. Materials and Methods We analyzed CT Perfusion data with 48 seconds and extended acquisition times, assuring full time attenuation curves, of 36 patients. Time attenuation curves were classified as complete or truncated. Ischemic core and penumbra volumes resulting from both data sets were compared by median paired differences and interquartile ranges. Controlled experiments were performed using a digital CT Perfusion phantom to investigate the effect of time attenuation curve truncation on ischemic core and penumbra estimation. Results In 48 seconds acquisition data, truncation was observed in 24 (67%) cases for the time attenuation curves in the ischemic core, in 2 cases for the arterial input function and in 5 cases for the venous output function. Analysis of extended data resulted in smaller ischemic cores and larger penumbras with a median difference of 13.2 (IQR: 4.3–26.0)ml (P<0.001) and; 12.4 (IQR: 4.1–25.7)ml (P<0.001), respectively. The phantom data showed increasing ischemic core overestimation with increasing tissue time attenuation curve truncation. Conclusions Truncation is common in patients with large vessel occlusion and results in repartitioning of the area of hypoperfusion into larger ischemic core and smaller penumbra estimations. Phantom experiments confirmed that truncation results in overestimation of the ischemic core. PMID

  1. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms.

    PubMed

    Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-12-01

    Ischemic conditioning is an intrinsic protective mechanism in which repeated short episodes of reversible ischemia protects the tissue and increases its tolerance against a subsequent longer period of ischemia (index ischemia). Bradykinin is a physiologically and pharmacologically active peptide of the kallikrein-kinin system. Besides the involvement of bradykinin in a variety of physiological and pathological responses such as pain, inflammation and in cardiovascular system as a potent vasodilator, it also acts as an endogenous cytoprotective mediator in the ischemic tissue. Pretreatment with various pharmacological modulators of bradykinin has confirmed the involvement of bradykinin in ischemic conditioning-induced protection. The protective actions of bradykinin in three major paradigms of ischemic conditioning i.e. ischemic preconditioning, ischemic postconditioning and remote ischemic preconditioning involves activation and regulation of various endogenous signaling cascades to render the heart resistant to infarction. In ischemic preconditioning, bradykinin exerts cardioprotective effect via activation of PI3K/Akt/eNOS signaling pathway and regulation of redox state via NO release. The role of bradykinin and its B2 receptors in ischemic-postconditioning induced neuroprotection has been described mainly due to its increased redox signaling cascade and activation of mitochondrial anti-apoptotic pathway. Furthermore, its cardioprotective role during remote ischemic preconditioning has been associated with activation of B2 receptors mediated neurogenic pathway and internalization of B2 receptors along with the formation of signalosomes that activates intracellular cytoprotective transduction pathways. The present review focuses on the potential role of bradykinin in mediating different forms of ischemic conditioning (pre/post/remote)-induced cardioprotection and neuroprotection along with the possible mechanisms. PMID:26499976

  2. Platelet neuropeptide Y is critical for ischemic revascularization in mice

    PubMed Central

    Tilan, Jason U.; Everhart, Lindsay M.; Abe, Ken; Kuo-Bonde, Lydia; Chalothorn, Dan; Kitlinska, Joanna; Burnett, Mary Susan; Epstein, Stephen E.; Faber, James E.; Zukowska, Zofia

    2013-01-01

    We previously reported that the sympathetic neurotransmitter neuropeptide Y (NPY) is potently angiogenic, primarily through its Y2 receptor, and that endogenous NPY is crucial for capillary angiogenesis in rodent hindlimb ischemia. Here we sought to identify the source of NPY responsible for revascularization and its mechanisms of action. At d 3, NPY−/− mice demonstrated delayed recovery of blood flow and limb function, consistent with impaired collateral conductance, while ischemic capillary angiogenesis was reduced (∼70%) at d 14. This biphasic temporal response was confirmed by 2 peaks of NPY activation in rats: a transient early increase in neuronally derived plasma NPY and increase in platelet NPY during late-phase recovery. Compared to NPY-null platelets, collagen-activated NPY-rich platelets were more mitogenic (∼2-fold vs. ∼1.6-fold increase) for human microvascular endothelial cells, and Y2/Y5 receptor antagonists ablated this difference in proliferation. In NPY+/+ mice, ischemic angiogenesis was prevented by platelet depletion and then restored by transfusion of platelets from NPY+/+ mice, but not NPY−/− mice. In thrombocytopenic NPY−/− mice, transfusion of wild-type platelets fully restored ischemia-induced angiogenesis. These findings suggest that neuronally derived NPY accelerates the early response to femoral artery ligation by promoting collateral conductance, while platelet-derived NPY is critical for sustained capillary angiogenesis.—Tilan, J. U., Everhart, L. M., Abe, K., Kuo-Bonde, L., Chalothorn, D., Kitlinska, J., Burnett, M. S., Epstein, S. E., Faber, J. E., Zukowska, Z. Platelet neuropeptide Y is critical for ischemic revascularization in mice. PMID:23457218

  3. Magnetic resonance imaging in acute ischemic stroke treatment.

    PubMed

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven; Kang, Dong-Wha

    2014-09-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  4. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection

    PubMed Central

    Cowan, Douglas B.; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R.; Thedsanamoorthy, Jerusha K.; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; del Nido, Pedro J.; Packard, Alan B.

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  5. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  6. A more consistent intraluminal rhesus monkey model of ischemic stroke

    PubMed Central

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726

  7. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection.

    PubMed

    Cowan, Douglas B; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R; Thedsanamoorthy, Jerusha K; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; Del Nido, Pedro J; Packard, Alan B; McCully, James D

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  8. Sex stratified neuronal cultures to study ischemic cell death pathways.

    PubMed

    Fairbanks, Stacy L; Vest, Rebekah; Verma, Saurabh; Traystman, Richard J; Herson, Paco S

    2013-01-01

    Sex differences in neuronal susceptibility to ischemic injury and neurodegenerative disease have long been observed, but the signaling mechanisms responsible for those differences remain unclear. Primary disassociated embryonic neuronal culture provides a simplified experimental model with which to investigate the neuronal cell signaling involved in cell death as a result of ischemia or disease; however, most neuronal cultures used in research today are mixed sex. Researchers can and do test the effects of sex steroid treatment in mixed sex neuronal cultures in models of neuronal injury and disease, but accumulating evidence suggests that the female brain responds to androgens, estrogens, and progesterone differently than the male brain. Furthermore, neonate male and female rodents respond differently to ischemic injury, with males experiencing greater injury following cerebral ischemia than females. Thus, mixed sex neuronal cultures might obscure and confound the experimental results; important information might be missed. For this reason, the Herson Lab at the University of Colorado School of Medicine routinely prepares sex-stratified primary disassociated embryonic neuronal cultures from both hippocampus and cortex. Embryos are sexed before harvesting of brain tissue and male and female tissue are disassociated separately, plated separately, and maintained separately. Using this method, the Herson Lab has demonstrated a male-specific role for the ion channel TRPM2 in ischemic cell death. In this manuscript, we share and discuss our protocol for sexing embryonic mice and preparing sex-stratified hippocampal primary disassociated neuron cultures. This method can be adapted to prepare sex-stratified cortical cultures and the method for embryo sexing can be used in conjunction with other protocols for any study in which sex is thought to be an important determinant of outcome. PMID:24378980

  9. [Ischemic stroke in childhood. A complication of tonsillectomy].

    PubMed

    Matilla Álvarez, A; García Serrano, E; González de la Huebra Labrador, T; Morales Martín, A C; Yusta Martín, G; Vaquero Roncero, L M

    2016-02-01

    Tonsillectomy is one of the most frequently performed otorhinolaryngological procedures on children. The postoperative complications are classified into primary or intermediate, which generally appear within 24h, and as secondary or delayed, after 48 h. We present the case of an ischemic stroke after performing a tonsillectomy on a 3 year-old boy, which was diagnosed in the immediate postoperative period. Using brain echo-doppler and angio-CT, an intraluminal clot was observed in the left internal carotid artery, probably as a result of direct vessel injury during arterial ligature for hemostasis. PMID:26025286

  10. Anton's Syndrome due to Bilateral Ischemic Occipital Lobe Strokes

    PubMed Central

    Zukić, Sanela; Sinanović, Osman; Hodžić, Renata; Mujagić, Svjetlana; Smajlović, Edina

    2014-01-01

    We present a case of a patient with Anton's syndrome (i.e., visual anosognosia with confabulations), who developed bilateral occipital lobe infarct. Bilateral occipital brain damage results in blindness, and patients start to confabulate to fill in the missing sensory input. In addition, the patient occasionally becomes agitated and talks to himself, which indicates that, besides Anton's syndrome, he might have had Charles Bonnet syndrome, characterized by both visual loss and hallucinations. Anton syndrome, is not so frequent condition and is most commonly caused by ischemic stroke. In this particular case, the patient had successive bilateral occipital ischemia as a result of massive stenoses of head and neck arteries. PMID:25530893

  11. Anton's Syndrome due to Bilateral Ischemic Occipital Lobe Strokes.

    PubMed

    Zukić, Sanela; Sinanović, Osman; Zonić, Lejla; Hodžić, Renata; Mujagić, Svjetlana; Smajlović, Edina

    2014-01-01

    We present a case of a patient with Anton's syndrome (i.e., visual anosognosia with confabulations), who developed bilateral occipital lobe infarct. Bilateral occipital brain damage results in blindness, and patients start to confabulate to fill in the missing sensory input. In addition, the patient occasionally becomes agitated and talks to himself, which indicates that, besides Anton's syndrome, he might have had Charles Bonnet syndrome, characterized by both visual loss and hallucinations. Anton syndrome, is not so frequent condition and is most commonly caused by ischemic stroke. In this particular case, the patient had successive bilateral occipital ischemia as a result of massive stenoses of head and neck arteries. PMID:25530893

  12. Mechanisms of Neurovascular Dysfunction in Acute Ischemic Brain

    PubMed Central

    Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L.D.; Lo, E.H.; Ji, X.; Arai, K.

    2014-01-01

    The neurovascular unit is now well accepted as a conceptual framework for investigating the mechanisms of ischemic stroke. From a molecular and cellular perspective, three broad mechanisms may underlie stroke pathophysiology – excitotoxicity, oxidative stress and inflammation. To date, however, most investigations of these basic mechanisms have focused on neuronal responses. In this mini-review, we ask whether these mechanisms of excitotoxicity, oxidative stress and inflammation can also be examined in terms of non-neuronal interactions in the neurovascular unit, including the release of extracellular vesicles for cell-cell signaling. PMID:24372202

  13. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    SciTech Connect

    Li, Zhao; Jin, Zhu-Qiu

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC

  14. Sex differences in predictors of ischemic stroke: current perspectives

    PubMed Central

    Samai, Alyana A; Martin-Schild, Sheryl

    2015-01-01

    Globally, stroke is a significant public health concern affecting more than 33 million individuals. Of growing importance are the differences between males and females in the predictors and overall risk of stroke. Given that women have a higher lifetime risk for stoke and account for more than half of all stroke deaths, sex-specific stroke risk factors merit investigation and may help target public health interventions. This review aims to discuss the current body of knowledge regarding sex-specific predictors of ischemic stroke including both modifiable and non-modifiable risk factors, as well as specific pathologies known to increase stroke risk. PMID:26251609

  15. Novel Thrombolytics for Acute Ischemic Stroke: Challenges and Opportunities.

    PubMed

    Logallo, Nicola; Kvistad, Christopher E; Nacu, Aliona; Thomassen, Lars

    2016-02-01

    Progress in finding a better alternative to alteplase has been slow. Tenecteplase and desmoteplase have better pharmacological profiles compared with alteplase, but definite clinical evidence of their superiority is lacking. The two major phase III studies that have tested the efficacy and safety of desmoteplase in ischemic stroke patients have shown neutral results and a promising safety profile, but the trials compared desmoteplase with placebo only in late admitted patients. Future trials should focus on testing novel thrombolytics in the early time window either as the sole acute recanalizing treatment or combined with thrombectomy. PMID:26798040

  16. Optical spectroscopy for the detection of ischemic tissue injury

    DOEpatents

    Demos, Stavros; Fitzgerald, Jason; Troppmann, Christoph; Michalopoulou, Andromachi

    2009-09-08

    An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient's body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

  17. Morphometry of an Ischemic Lesion of Cat Spinal Cord

    PubMed Central

    Shay, Jonathan

    1973-01-01

    Profiles in random electron micrographs of anterior gray matter of normal and ischemic cat spinal cord were measured with a planimetric computer. Analysis of 5600 area measurements revealed the following differences. Mitochondria of neuron cell bodies, axons, axon terminals and astrocytic processes were two to three times larger after ischemia. However, only 15% of mitochondria of axons and axon terminals and 5% of astrocytic processes lost their matrix density and pattern of cristae, compared to 49% of mitochondria of neuron cell bodies. Ischemia caused no significant changes in mean sizes of axons or axon terminals. Lysosomes in neurons were unchanged. The mean size of astrocytic processes increased more than threefold. PMID:4728890

  18. Ischemic Preconditioning and Placebo Intervention Improves Resistance Exercise Performance.

    PubMed

    Marocolo, Moacir; Willardson, Jeffrey M; Marocolo, Isabela C; Ribeiro da Mota, Gustavo; Simão, Roberto; Maior, Alex S

    2016-05-01

    Marocolo, M, Willardson, JM, Marocolo, IC, da Mota, GR, Simão, R, and Maior, AS. Ischemic preconditioning and PLACEBO intervention improves resistance exercise performance. J Strength Cond Res 30(5): 1462-1469, 2016-This study evaluated the effect of ischemic preconditioning (IPC) on resistance exercise performance in the lower limbs. Thirteen men participated in a randomized crossover design that involved 3 separate sessions (IPC, PLACEBO, and control). A 12-repetition maximum (12RM) load for the leg extension exercise was assessed through test and retest sessions before the first experimental session. The IPC session consisted of 4 cycles of 5 minutes of occlusion at 220 mm Hg of pressure alternated with 5 minutes of reperfusion at 0 mm Hg for a total of 40 minutes. The PLACEBO session consisted of 4 cycles of 5 minutes of cuff administration at 20 mm Hg of pressure alternated with 5 minutes of pseudo-reperfusion at 0 mm Hg for a total of 40 minutes. The occlusion and reperfusion phases were conducted alternately between the thighs, with subjects remaining seated. No ischemic pressure was applied during the control (CON) session and subjects sat passively for 40 minutes. Eight minutes after IPC, PLACEBO, or CON, subjects performed 3 repetition maximum sets of the leg extension (2-minute rest between sets) with the predetermined 12RM load. Four minutes after the third set for each condition, blood lactate was assessed. The results showed that for the first set, the number of repetitions significantly increased for both the IPC (13.08 ± 2.11; p = 0.0036) and PLACEBO (13.15 ± 0.88; p = 0.0016) conditions, but not for the CON (11.88 ± 1.07; p > 0.99) condition. In addition, the IPC and PLACEBO conditions resulted insignificantly greater repetitions vs. the CON condition on the first set (p = 0.015; p = 0.007) and second set (p = 0.011; p = 0.019), but not on the third set (p = 0.68; p > 0.99). No difference (p = 0.465) was found in the fatigue index and lactate

  19. Pathobiology of Ischemic Heart Disease: Past, Present and Future.

    PubMed

    Buja, L Maximilian; Vander Heide, Richard S

    2016-01-01

    This review provides a perspective on knowledge of ischemic heart disease (IHD) obtained from the contemporary era of research which began in the 1960s and has continued to the present day. Important discoveries have been made by basic and translational scientists and clinicians. Pathologists have contributed significantly to insights obtained from experimental studies and clinicopathological studies in humans. The review also provides a perspective for future directions in research in IHD aimed at increasing basic knowledge and developing additional therapeutic options for patients with IHD. PMID:26897485

  20. Adolescent ischemic stroke associated with anabolic steroid and cannabis abuse.

    PubMed

    El Scheich, Tarik; Weber, Artur-Aron; Klee, Dirk; Schweiger, Daniel; Mayatepek, Ertan; Karenfort, Michael

    2013-01-01

    We report on a 16-year-old body builder who suffered from an acute ischemic stroke. In the urine, cannabis metabolites as well as metabolites of the oral androgenic-anabolic steroid methandrostenolone were detected, both known to be associated with stroke events. This report highlights the role of cannabis and steroid abuse that induce strokes in the absence of arteriopathy, cardioembolism or thrombophilia. Owing to new upcoming socio-behavioral aspects of late childhood and early adolescent life, this formally rare abuse of cannabis and/or anabolic steroids as well as their associations with strokes becomes more current than ever. PMID:23382306

  1. NINJ2 polymorphism is associated with ischemic stroke in Chinese Han population.

    PubMed

    Wan, Xin-hong; Li, Shu-juan; Cheng, Ping; Zhang, Qi; Yang, Xin-chun; Zhong, Guang-zhen; Hu, Wen-li; Jin, Li; Wang, Xiao-feng

    2011-09-15

    Recently, a genome-wide association study reported an association between two single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important candidate locus in the prevalence of ischemic stroke. We performed a hospital based genetic association study in Chinese Han subjects to investigate the relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924 control subjects and conducted the association between these tSNPs and ischemic stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene significantly associated with ischemic stroke (both genotype and allelic p=0.0001). The minor A allele increased the risk of ischemic stroke with a per-allele OR of 1.37 for the additive genetic model in univariate analysis (p=0.0001). The significance remained after adjustment for the covariates of age, gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes. Therefore, we report a new genetic variant, rs10849373, located in the first intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han subjects. Further genetic association and functional studies are required to search the causal functional variant in linkage disequilibrium with this polymorphism. PMID:21722921

  2. Ionic storm in hypoxic/ischemic stress: Can opioid receptors subside it?

    PubMed Central

    Chao, Dongman; Xia, Ying

    2010-01-01

    Neurons in the mammalian central nervous system are extremely vulnerable to oxygen deprivation and blood supply insufficiency. Indeed, hypoxic/ischemic stress triggers multiple pathophysiological changes in the brain, forming the basis of hypoxic/ischemic encephalopathy. One of the initial and crucial events induced by hypoxia/ischemia is the disruption of ionic homeostasis characterized by enhanced K+ efflux and Na+-, Ca2+- and Cl− influx, which causes neuronal injury or even death. Recent data from our laboratory and those of others have shown that activation of opioid receptors, particularly δ-opioid receptors (DOR), is neuroprotective against hypoxic/ischemic insult. This protective mechanism may be one of the key factors that determine neuronal survival under hypoxic/ischemic condition. An important aspect of the DOR-mediated neuroprotection is its action against hypoxic/ischemic disruption of ionic homeostasis. Specially, DOR signal inhibits Na+ influx through the membrane and reduces the increase in intracellular Ca2+, thus decreasing the excessive leakage of intracellular K+. Such protection is dependent on a PKC-dependent and PKA-independent signaling pathway. Furthermore, our novel exploration shows that DOR attenuates hypoxic/ischemic disruption of ionic homeostasis through the inhibitory regulation of Na+ channels. In this review, we will first update current information regarding the process and features of hypoxic/ischemic disruption of ionic homeostasis and then discuss the opioid-mediated regulation of ionic homeostasis, especially in hypoxic/ischemic condition, and the underlying mechanisms. PMID:20036308

  3. Myricetin and quercetin attenuate ischemic injury in glial cultures by different mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have demonstrated that polyphenols from cinnamon and green tea reduce cell swelling and mitochondrial dysfunction in C6 glial cultures following ischemic injury. We tested the protective effects of the flavonoid polyphenols, myricetin and quercetin, on key features of ischemic injury. C6 cultures...

  4. Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat model of ischemic stroke.

    PubMed

    Yoo, Jongman; Seo, Jin-Ju; Eom, Jang-Hyeon; Hwang, Dong-Youn

    2015-01-01

    Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Thrombolytic drugs effectively treat the very acute stage of stroke, and several neuroprotectants that are designed to treat secondary injury following stroke are being tested in clinical trials. However, these pharmacological approaches primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In recent years, stem cell-mediated regenerative approaches have emerged as promising therapeutic strategies for treating the chronic stage of stroke. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. Our transplantation experiments using BMCs obtained from ischemic donor rats showed functional and structural recovery during the chronic stage of stroke. BMC-mediated neural proliferation was prominent in the brains of rats with chronic stroke, and most of the new cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neural proliferation coincided with a significant reduction (∼50%) in the number of activated microglia, which is consistent with previous reports of enhanced neural proliferation being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, suggesting that these cells may exert the beneficial effects associated with BMC transplantation. Based on the reported anti-inflammatory role of CD25(+) regulatory T-cells in acute experimental stroke, we propose a working model delineating the positive effects of BMC transplantation during the chronic phase of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, which leads to enhanced neural proliferation and enhanced recovery from neuronal damage in this rat model of chronic stroke. This study provides valuable insights into the effect

  5. Aspirin Resistance in the Acute Stages of Acute Ischemic Stroke Is Associated with the Development of New Ischemic Lesions

    PubMed Central

    Kim, Joon-Tae; Heo, Suk-Hee; Lee, Ji Sung; Choi, Min-Ji; Choi, Kang-Ho; Nam, Tai-Seung; Lee, Seung-Han; Park, Man-Seok; Kim, Byeong C.; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2015-01-01

    Background Aspirin is a primary antiplatelet agent for the secondary prevention of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is expected in acute ischemic stroke (AIS), it may increase the rate of early clinical events. Therefore, we sought to determine whether aspirin resistance in the acute stage was associated with early radiological events, including new ischemic lesions (NILs). Methods This study was a single-center, prospective, observational study conducted between April 2012 and May 2013. Aspirin 300 mg was initially administered followed by maintenance doses of 100 mg daily. The acute aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin loading. An aARU value ≥550 IU was defined as biological aspirin resistance (BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions separate from index lesions, which were not detected on the initial DWI. Results A total of 367 patients were analyzed in this study. BAR in aARU was detected in 60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were frequently in the same territory as the index lesions (79%), pial infarcts (61.7%), and located within the cortex (59.3%). BAR was independently associated with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01–3.96; p = 0.047). Conclusion In conclusion, BAR in aARU could be associated with NILs on follow-up DWI in AIS. Therefore, a further prospective study with a longer follow-up period is necessary to evaluate the clinical implications of aARU in AIS. PMID:25849632

  6. Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Patel, Priyesh A.; Zhao, Xin; Fonarow, Gregg C.; Lytle, Barbara L.; Smith, Eric E.; Xian, Ying; Bhatt, Deepak L.; Peterson, Eric D.; Schwamm, Lee H.; Hernandez, Adrian F.

    2015-01-01

    Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized. Methods and Results Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc). Conclusions NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin. PMID:26058721

  7. History, Evolution, and Importance of Emergency Endovascular Treatment of Acute Ischemic Stroke.

    PubMed

    Holodinsky, Jessalyn K; Yu, Amy Y X; Assis, Zarina A; Al Sultan, Abdulaziz S; Menon, Bijoy K; Demchuk, Andrew M; Goyal, Mayank; Hill, Michael D

    2016-05-01

    More than 800,000 people in North America suffer a stroke each year, with ischemic stroke making up the majority of these cases. The outcomes of ischemic stroke range from complete functional and cognitive recovery to severe disability and death; outcome is strongly associated with timely reperfusion treatment. Historically, ischemic stroke has been treated with intravenous thrombolytic agents with moderate success. However, five recently published positive trials have established the efficacy of endovascular treatment in acute ischemic stroke. In this review, we will discuss the history of stroke treatments moving from various intravenous thrombolytic drugs to intra-arterial thrombolysis, early mechanical thrombectomy devices, and finally modern endovascular devices. Early endovascular therapy failures, recent successes, and implications for current ischemic stroke management and future research directions are discussed. PMID:27021771

  8. εPKC confers acute tolerance to cerebral ischemic reperfusion injury

    PubMed Central

    Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

    2008-01-01

    In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

  9. The P2X4 receptor is required for neuroprotection via ischemic preconditioning

    PubMed Central

    Ozaki, Tomohiko; Muramatsu, Rieko; Sasai, Miwa; Yamamoto, Masahiro; Kubota, Yoshiaki; Fujinaka, Toshiyuki; Yoshimine, Toshiki; Yamashita, Toshihide

    2016-01-01

    Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance. PMID:27173846

  10. Minor Stroke and Transient Ischemic Attack: Research and Practice

    PubMed Central

    Yakhkind, Aleksandra; McTaggart, Ryan A.; Jayaraman, Mahesh V.; Siket, Matthew S.; Silver, Brian; Yaghi, Shadi

    2016-01-01

    A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID:27375548

  11. Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review

    PubMed Central

    Ding, Zheng; Tong, Wesley C.; Lu, Xiao-Xin; Peng, Hui-Ping

    2014-01-01

    Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window. PMID:25337089

  12. Protective effects of remote ischemic preconditioning in isolated rat hearts

    PubMed Central

    Teng, Xiao; Yuan, Xin; Tang, Yue; Shi, Jingqian

    2015-01-01

    To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID:26550168

  13. Suppression of Etk/Bmx protects against ischemic brain injury.

    PubMed

    Chen, Kai-Yun; Wu, Chung-Che; Chang, Cheng-Fu; Chen, Yuan-Hao; Chiu, Wen-Ta; Lou, Ya-Hsin; Chen, Yen-Hua; Shih, Hsiu-Ming; Chiang, Yung-Hsiao

    2012-01-01

    Etk/Bmx (epithelial and endothelial tyrosine kinase, also known as BMX), a member of the Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of protein-tyrosine kinases, is an important regulator of signal transduction for the activation of cell growth, differentiation, and development. We have previously reported that activation of Etk leads to apoptosis in MDA-MB-468 cells. The purpose of this study was to examine the role of Etk in neuronal injury induced by H(2)O(2) or ischemia. Using Western blot analysis and immunohistochemistry, we found that treatment with H(2)O(2) significantly enhanced phosphorylation of Etk and its downstream signaling molecule Stat1 in primary cortical neurons. Inhibiting Etk activity by LFM-A13 or knocking down Etk expression by a specific shRNA increased the survival of primary cortical neurons. Similarly, at 1 day after a 60-min middle cerebral artery occlusion (MCAo) in adult rats, both phosphorylated Etk and Stat1 were coexpressed with apoptotic markers in neurons in the penumbra. Pretreatment with LFM-A13 or an adenoviral vector encoding the kinase deletion mutant Etkk attenuated caspase-3 activity and infarct volume in ischemic brain. All together, our data suggest that Etk is activated after neuronal injury. Suppressing Etk activity protects against neurodegeneration in ischemic brain. PMID:21929872

  14. Susceptibility of the pancreas to ischemic injury in shock.

    PubMed Central

    Warshaw, A L; O'Hara, P J

    1978-01-01

    The pancreas, like the kidney, is highly vulnerable to ischemic necrosis. This form of pancreatic injury may express itself as prolonged hyperamylasemia with only minimal signs or symptoms of inflammation, or may produce severe pancreatitis followed by abscesses and death. Autopsy examination of patients dying after oligemic shock showed a 9% incidence of major pancreatic injury if there was not concomitant acute renal tubular necrosis (ATN), but a 50% incidence in those with ATN. Similarly, among patients dying after non-oligemic shock, 12% of those without ATN had major pancreatic injury but 35% with ATN also had pancreatic ischemic injury. Among 13 selected patients examined prospectively after being in shock, pancreatic injury was indicated by hyperamylasemia, hyperlipasemia, elevated amylase/creatinine clearance ratio, and elevated circulating isoamylases specifically of pancreatic origin. Four of the 13 had clinical manifestations of pancreatitis. Not only must shock be added to this list of causes of pancreatitis, but pancreatic ischemia due to hypoperfusion may also be the critical factor which causes the progression from edema to necrosis in other forms of pancreatitis, including those associated with alcohol and biliary disease. PMID:686887

  15. HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

    PubMed Central

    Greco, Simona; Gaetano, Carlo

    2014-01-01

    Abstract Significance: MicroRNAs (miRNAs) are deregulated and play a causal role in numerous cardiovascular diseases, including myocardial infarction, coronary artery disease, hypertension, heart failure, stroke, peripheral artery disease, kidney ischemia–reperfusion. Recent Advances: One crucial component of ischemic cardiovascular diseases is represented by hypoxia. Indeed, hypoxia is a powerful stimulus regulating the expression of a specific subset of miRNAs, named hypoxia-induced miRNAs (hypoxamiR). These miRNAs are fundamental regulators of the cell responses to decreased oxygen tension. Certain hypoxamiRs seem to have a particularly pervasive role, such as miR-210 that is virtually induced in all ischemic diseases tested so far. However, its specific function may change according to the physiopathological context. Critical Issues: The discovery of HypoxamiR dates back 6 years. Thus, despite a rapid growth in knowledge and attention, a deeper insight of the molecular mechanisms underpinning hypoxamiR regulation and function is needed. Future Directions: An extended understanding of the function of hypoxamiR in gene regulatory networks associated with cardiovascular diseases will allow the identification of novel molecular mechanisms of disease and indicate the development of innovative therapeutic approaches. Antioxid. Redox Signal. 21, 1202–1219. PMID:24053126

  16. Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents.

    PubMed

    Brandli, Alice

    2015-01-01

    Sublethal ischemia protects tissues against subsequent, more severe ischemia through the upregulation of endogenous mechanisms in the affected tissue. Sublethal ischemia has also been shown to upregulate protective mechanisms in remote tissues. A brief period of ischemia (5-10 min) in the hind limb of mammals induces self-protective responses in the brain, lung, heart and retina. The effect is known as remote ischemic preconditioning (RIP). It is a therapeutically promising way of protecting vital organs, and is already under clinical trials for heart and brain injuries. This publication demonstrates a controlled, minimally invasive method of making a limb - specifically the hind limb of a rat - ischemic. A blood pressure cuff developed for use in human neonates is connected to a manual sphygmomanometer and used to apply 160 mmHg pressure around the upper part of the hind limb. A probe designed to detect skin temperature is used to verify the ischemia, by recording the drop in skin temperature caused by pressure-induced occlusion of the leg arteries, and the rise in temperature which follows release of the cuff. This method of RIP affords protection to the rat retina against bright light-induced damage and degeneration. PMID:26065365

  17. A patient with atonic seizures mimicking transient ischemic attacks

    PubMed Central

    Kang, Min-Ju; Choi, Jun Young; An, Young-Sil; Park, Ki-Hyung; Park, Hyeon-Mi; Lee, Yeong-Bae; Shin, Dong-Jin; Sung, Young Hee; Shin, Dong Hoon

    2015-01-01

    A focal atonic seizure is a partial seizure in which the ictal manifestation consists of paresis of the extremities or muscles on one side of the body, and this phenomenon can easily be misdiagnosed as a transient ischemic attack. An 86-year-old woman visited our hospital complaining of transient right upper extremity weakness lasting for 10 min following an unusual sensation in her chest accompanied by palpitations. On the third hospital day, she again complained of right arm weakness, which progressed to jerky movements of her right extremity accompanied by facial twitching and then generalized into a tonic–clonic seizure. The EEG displayed several interictal spikes in the contralateral temporal area, and the ictal SPECT, analyzed using the SISCOM system, showed an increased signal in both the contralateral superior parietal area and the mesial frontal area. In this case, the patient was diagnosed with focal atonic seizures as the cause of the monolimb weakness, which had been initially misdiagnosed aas transient ischemic attacks. In cases in which a patient presents with monolimb paresis, physicians should consider the possibility of an atonic seizure as the cause. PMID:25870790

  18. Concepts of hypoxic NO signaling in remote ischemic preconditioning

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike; Rassaf, Tienush

    2015-01-01

    Acute coronary syndromes remain a leading single cause of death worldwide. Therapeutic strategies to treat cardiomyocyte threatening ischemia/reperfusion injury are urgently needed. Remote ischemic preconditioning (rIPC) applied by brief ischemic episodes to heart-distant organs has been tested in several clinical studies, and the major body of evidence points to beneficial effects of rIPC for patients. The underlying signaling, however, remains incompletely understood. This relates particularly to the mechanism by which the protective signal is transferred from the remote site to the target organ. Many pathways have been forwarded but none can explain the protective effects completely. In light of recent experimental studies, we here outline the current knowledge relating to the generation of the protective signal in the remote organ, the signal transfer to the target organ and the transduction of the transferred signal into cardioprotection. The majority of studies favors a humoral factor that activates cardiomyocyte downstream signaling - receptor-dependent and independently. Cellular targets include deleterious calcium (Ca2+) signaling, reactive oxygen species, mitochondrial function and structure, and cellular apoptosis and necrosis. Following an outline of the existing evidence, we will furthermore characterize the existing knowledge and discuss future perspectives with particular emphasis on the interaction between the recently discovered hypoxic nitrite-nitric oxide signaling in rIPC. This refers to the protective role of nitrite, which can be activated endogenously using rIPC and which then contributes to cardioprotection by rIPC. PMID:26516418

  19. Amelioration of myocardial ischemic reperfusion injury with Calendula officinalis.

    PubMed

    Ray, Diptarka; Mukherjee, Subhendu; Falchi, Mario; Bertelli, Aldo; Das, Dipak K

    2010-12-01

    Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achieved cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degeneration diseases like ischemic heart disease. PMID:20874690

  20. Cardioprotection Acquired Through Exercise: The Role of Ischemic Preconditioning

    PubMed Central

    Marongiu, Elisabetta; Crisafulli, Antonio

    2014-01-01

    A great bulk of evidence supports the concept that regular exercise training can reduce the incidence of coronary events and increase survival chances after myocardial infarction. These exercise-induced beneficial effects on the myocardium are reached by means of the reduction of several risk factors relating to cardiovascular disease, such as high cholesterol, hypertension, obesity etc. Furthermore, it has been demonstrated that exercise can reproduce the “ischemic preconditioning” (IP), which refers to the capacity of short periods of ischemia to render the myocardium more resistant to subsequent ischemic insult and to limit infarct size during prolonged ischemia. However, IP is a complex phenomenon which, along with infarct size reduction, can also provide protection against arrhythmia and myocardial stunning due to ischemia-reperfusion. Several clues demonstrate that preconditioning may be directly induced by exercise, thus inducing a protective phenotype at the heart level without the necessity of causing ischemia. Exercise appears to act as a physiological stress that induces beneficial myocardial adaptive responses at cellular level. The purpose of the present paper is to review the latest data on the role played by exercise in triggering myocardial preconditioning. PMID:24720421

  1. Role of mitochondria in ischemic acute renal failure.

    PubMed

    Burke, T J; Wilson, D R; Levi, M; Gordon, J A; Arnold, P E; Schrier, R W

    1983-01-01

    Ischemic ARF is characterized by progressive mitochondrial accumulation of Ca++ which is inversely correlated with the level of oxidative phosphorylation. At least two possibilities exist which would be compatible with these data 1) depressed respiration leads to Ca++ accumulation or 2) increased mitochondrial Ca++ leads to reduced mitochondrial respiration. We favor the latter hypothesis for the reasons outlined above; furthermore, this conclusion is supported by the observations of Lehninger, made some 20 years ago: first, that either oxidative phosphorylation or mitochondrial Ca++ accumulation can be accomplished by intact mitochondria but that these events cannot occur simultaneously and second, that Ca++ accumulation takes precedence over oxidative phosphorylation. Our observation made during post-ischemic reflow that mitochondrial Ca++ accumulation occurs to a significant degree, strongly suggest a potential role for mitochondrial Ca++ overload in the pathogenesis of ARF. Nevertheless, this is not an irreversible pathogenetic process. Clearly, impermeant solutes, vasodilators and Ca++ membrane blockers will alter the natural history of this injury and prevent the severity of the functional defect. A common mechanism of action may involve direct or indirect modification of cellular Ca++ overload in renal vascular and epithelial tissue. The vascular smooth muscle may then revert to a less constricted state with a subsequent more rapid recovery of renal blood flow and that the renal epithelial cell death may be minimized thereby reducing tubular obstruction. PMID:6883804

  2. Neuroprotection in ischemic stroke: what does the future hold?

    PubMed

    Korczyn, Amos D; Brainin, Michael; Guekht, Alla

    2015-03-01

    Neurodegenerative and vascular disease processes are commonly found concurrently in the brains of elderly patients, highlighting the difficulty in determining which processes may be responsible for cognitive impairment. Therapeutically, it may be more sensible to assume that most patients have mixed dementia. Therefore, therapies with multimodal modes of action would be expected to confer neuronal protection. Ischemic stroke is also associated with a complex pathophysiology and a high incidence of post-stroke cognitive impairment, but evidence for the efficacy of neuroprotective treatments in humans is contradictory (mainly due to a failed translation from bench to bedside). Nevertheless, emerging drug therapies continue to undergo testing in prospective, randomized, controlled studies. Natural biologicals, such as Actovegin, or smaller biological molecules with multifaceted effects in the restorative phase of ischemia are likely candidates for efficacy testing. In addition, a number of non-pharmacological interventions, especially lifestyle interventions, are also the subject of current research and would eventually be expected to supplement the treatment and prevention of ischemic stroke. PMID:25708307

  3. Profile of prothrombotic factors in Indian children with ischemic stroke.

    PubMed

    Konanki, Ramesh; Gulati, Sheffali; Saxena, Renu; Gupta, Arun Kumar; Seith, Ashu; Kumar, Ashok; Saxena, Anita; Kabra, Madhulika; Kalra, Veena; Lakshmy, Ramakrishnan

    2014-08-01

    This study was undertaken in view of paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities. PMID:24629397

  4. Effects of topical oxygen therapy on ischemic wound healing

    PubMed Central

    Rao, Congqiang; Xiao, Liling; Liu, Hongwei; Li, Shenghong; Lu, Jinqiang; Li, Jiangxuan; Gu, Shixing

    2016-01-01

    [Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing. PMID:26957741

  5. Ryanodine receptors contribute to the induction of ischemic tolerance.

    PubMed

    Nakamura-Maruyama, Emi; Miyamoto, Osamu; Okabe, Naohiko; Himi, Naoyuki; Feng, Lu; Narita, Kazuhiko; Keep, Richard F; Yamamoto, Tohru; Nakamura, Takehiro

    2016-04-01

    Ischemic tolerance (IT) is induced by a variety of insults to the brain (e.g., nonfatal ischemia, heat and hypoxia) and it provides a strong neuroprotective effect. Although the mechanisms are still not fully elucidated, Ca(2+) is regarded as a key mediator of IT. Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores. In brain, neuronal RyRs are thought to play a role in various neuropathological conditions, including ischemia. The purpose of the present study was to investigate the involvement of RyRs in IT. Pretreatment with a RyR antagonist, dantrolene (25mg/kg, i.p), blocked IT in a gerbil global ischemia model, while a RyR agonist, caffeine (100mg/kg, i.p), stimulated the production of IT. In vitro, using rat hippocampal cells, short-term oxygen/glucose deprivation induced preconditioning and RyR antagonists, dantrolene (50 and 100μM) and ryanodine (100 and 200μM) prevented it. RyR protein and mRNA levels were transiently decreased after induction of IT. These results suggest that RyRs are involved in the induction of ischemic tolerance. PMID:26930163

  6. Failure of interventions to maintain mitochondrial function in ischemic myocardium.

    PubMed

    Clements, I P; Dewey, J D; Harrison, C E

    1980-10-01

    The purpose of this study was to investigate whether pyruvate (2.5 mmol/kg), the combination of glucose (3.9 mmol/kg) and insulin (0.13 unit/kg) with potassium (9.27 meq/kg), or sodium dichloroacetate (120 mg/kg) infused for 15 minutes before and 20 minutes after ligation of the left anterior descending coronary arterv in anesthetized dogs restricted the depression in mitochondrial respiratory function induced by ischemia. Myocardial blood flow after ligation in the three groups was o.2 ml/min per gram or less in ischemic subendocardium and was similar to that in saline-infused controls that had also undergone coronary artery ligation. The depressions induced in mitochondrial respiratory control index and state 3 respiration by ischemia in the subendocardium and subepicardium of the three treatment groups, when compared with corresponding nonischemic tissue, were not significantly improved from the control values. It was concluded that these three interventions fail to preserve mitochondrial respiration in ischemic myocardium. PMID:6997645

  7. Endogenous Erythropoietin Protects Neuroretinal Function in Ischemic Retinopathy

    PubMed Central

    Mowat, Freya M.; Gonzalez, Francisco; Luhmann, Ulrich F.O.; Lange, Clemens A.; Duran, Yanai; Smith, Alexander J.; Maxwell, Patrick H.; Ali, Robin R.; Bainbridge, James W.B.

    2012-01-01

    Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. PMID:22342523

  8. Minor Stroke and Transient Ischemic Attack: Research and Practice.

    PubMed

    Yakhkind, Aleksandra; McTaggart, Ryan A; Jayaraman, Mahesh V; Siket, Matthew S; Silver, Brian; Yaghi, Shadi

    2016-01-01

    A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID:27375548

  9. Ischemic hepatitis after percutaneous nephrolitotomy: A case report

    PubMed Central

    Temiz, Mustafa Zafer; Yuruk, Emrah; Teberik, Kutlu; Akbas, Burcu Kadriye; Piroglu, Mustafa Devrim; Oztorun, Hande Selvi; Kandirali, Engin

    2014-01-01

    INTRODUCTION Ischemic hepatitis (IH) is the necrosis of the centrilobular hepatocytes of liver and is secondary to liver hypoperfusion in most of the cases. The diagnosis is usually based on biochemical findings due to the absence of symptoms and signs. Although the disease course is often mild, and sometimes is even not diagnosed, the outcome is poor if the etiology of hypotension and liver anoxia is not promptly corrected. PRESENTATION OF CASE A 64-year-old patient who underwent percutaneous nephrolithotomy (PNL) for right renal pelvic stone developed acute IH at first postoperative day as a result of hemorrhage related severe hypotension. After restoring hemodynamic parameters, she completely recovered 2 weeks after the operation. DISCUSSION IH is a frequent cause of marked serum aminotransferase elevation and most commonly occurs as a result of arterial hypoxemia and insufficient hepatic perfusion. Although no specific treatment of IH exists, stabilizing the hemodynamic parameters of the patient resolves the problem in most of the cases. CONCLUSION This case is presented to demonstrate that ischemic hepatitis should be kept in mind if severe hemorrhage occurs during PNL. PMID:25437690

  10. Remote Ischemic Postconditioning (RIPC) After GMH in Rodents.

    PubMed

    Lekic, Tim; Klebe, Damon; Flores, Jerry; Peters, Regina; Rolland, William B; Tang, Jiping; Zhang, John H

    2016-01-01

    Germinal matrix hemorrhage (GMH) is the most common and devastating neurological injury of premature infants, and current treatment approaches are ineffective. Remote ischemic postconditioning (RIPC) is a method by which brief limb ischemic stimuli protect the injured brain. We hypothesized that RIPC can improve outcomes following GMH in rats. Neonatal rats (P7) were subjected to either stereotactic ganglionic eminence collagenase infusion or sham surgery. Groups were as follows: sham (n = 0), GMH non-RIPC (n = 10), GMH + 1 week RIPC (n = 10), GMH + 2 weeks RIPC (n = 10). Neurobehavior analysis at the fourth week consisted of Morris water maze (MWM) and rotarod (RR). This was followed by euthanasia for histopathology on day 28. Both 1- and 2-week RIPC showed significant improvement in FF and RR motor testing compared with untreated animals (i.e., GMH without RIPC). RIPC treatment also improved cognition (MWM) and attenuated neuropathological ventricular enlargement (hydrocephalus) in juvenile animals following GMH. RIPC is a safe and noninvasive approach that improved sensorimotor and neuropathological outcomes following GMH in rats. Further studies are needed to evaluate for mechanisms of neuroprotection. PMID:26463924

  11. Remote Ischemic Preconditioning (RIPC) Modifies Plasma Proteome in Humans

    PubMed Central

    Hepponstall, Michele; Ignjatovic, Vera; Binos, Steve; Monagle, Paul; Jones, Bryn; Cheung, Michael H. H.; d’Udekem, Yves; Konstantinov, Igor E.

    2012-01-01

    Remote Ischemic Preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against multi-organ damage by ischemia-reperfusion (IR). Although it has been demonstrated that RIPC affects gene expression, the proteomic response to RIPC has not been determined. This study aimed to examine RIPC induced changes in the plasma proteome. Five healthy adult volunteers had 4 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Blood samples were taken from the ipsilateral arm prior to first ischaemia, immediately after each episode of ischemia as well as, at 15 min and 24 h after the last episode of ischemia. Plasma samples from five individuals were analysed using two complementary techniques. Individual samples were analysed using 2Dimensional Difference in gel electrophoresis (2D DIGE) and mass spectrometry (MS). Pooled samples for each of the time-points underwent trypsin digestion and peptides generated were analysed in triplicate using Liquid Chromatography and MS (LC-MS). Six proteins changed in response to RIPC using 2D DIGE analysis, while 48 proteins were found to be differentially regulated using LC-MS. The proteins of interest were involved in acute phase response signalling, and physiological molecular and cellular functions. The RIPC stimulus modifies the plasma protein content in blood taken from the ischemic arm in a cumulative fashion and evokes a proteomic response in peripheral blood. PMID:23139772

  12. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

    PubMed Central

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34+ and CD 133+ stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future. PMID:26101528

  13. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease

    PubMed Central

    Akar, Fadi G.

    2015-01-01

    Mitochondrial dysfunction is a hallmark of multiple cardiovascular disorders, including ischemic heart disease. Although mitochondria are well recognized for their role in energy production and cell death, mechanisms by which they control excitation-contraction coupling, excitability, and arrhythmias are less clear. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is expressed in multiple organ systems. The abundant expression of TSPO in macrophages has been leveraged to image the immune response of the heart to inflammatory processes. More recently, the recognition of TSPO as a regulator of energy-dissipating mitochondrial pathways has extended its utility from a diagnostic marker of inflammation to a therapeutic target influencing diverse pathophysiological processes. Here, we provide an overview of the emerging role of TSPO in ischemic heart disease. We highlight the importance of TSPO in the regenerative process of reactive oxygen species (ROS) induced ROS release through its effects on the inner membrane anion channel (IMAC) and the permeability transition pore (PTP). We discuss evidence implicating TSPO in arrhythmogenesis in the settings of acute ischemia-reperfusion injury and myocardial infarction. PMID:25918579

  14. Ischemic Gangrene of the Glans following Penile Prosthesis Implantation

    PubMed Central

    García Gómez, Borja; Romero Otero, Javier; Díez Sicilia, Laura; Jiménez Alcaide, Estibaliz; García-Cruz, Eduardo; Rodríguez Antolín, Alfredo

    2013-01-01

    The development of ischemic gangrene of the penis following implantation of prosthesis is unusual, and very few cases are available in the literature. As a result, no established treatment protocol is available. We report our experience within a case of gangrene of the glans following implantation of a three-component prosthesis. We present a 53-year-old male, smoker with diabetes and hypercholesterolemia, who underwent surgery for the insertion of a penile prosthesis with 3 components to correct his erectile dysfunction and severe Peyronie's disease. The procedure was carried out without incidents. During the postoperative period, the patient began to complain from penile and perineal pain. He developed avascular necrosis of the glans. The necrosed area was excised. Four weeks later, he developed fever and perineal pain arriving to the emergency room with the prosthesis extruding through the glans. He had emergency surgery to remove the prosthesis plus surgical lavage and was prescribed broad-spectrum antibiotic therapy. Four weeks later, the penis was completely revascularized and reepithelialized. Ischemic gangrene following penile prosthesis implantation takes place in patients with poor peripheral vascularisation. Diabetes mellitus has been the common denominator to all of the reported cases. PMID:23956919

  15. [PROBLEM OF END EFFECTOR OF ISCHEMIC POSTCONDITIONING OF THE HEART].

    PubMed

    Maslov, L N; Naryzhnaya, N V; Pei, J-M; Zhang, Y; Wang, H; Khaliulin, I J; Lishmanov, Yu B

    2015-06-01

    It is well known that cardiovascular disease and in particular acute myocardial infarction are a major cause of death among working-age population in Russia. Some of the patients die after successful recanalization of the infarct-related coronary artery as a result of ischemic and reperfusion injury of the heart. It is obvious that there is an urgent need to develop new approaches to prevention reoxygenation heart damages. In this regard the study of adaptive phenomenon postconditioning is of particular interest. This analysis of literature source preformed by authors of the article indicates that main pretenders to the role of end-effectors of ischemic postconditioning of the heart are: (1) Ca(2+)-dependent K+ channel of BK-type (big conductance K+ channel), (2) mitoKATp channel (mitochondrial ATP-sensitive K+ channel), (3) MPT pore (mitochondrial permeability transition pore). At the same time, some investigators consider that mitoK(ATP) channel is only an intermediate link in the series of signaling events ensured an increase in cardiac tolerance to impact of ischemia-reperfusion. The most likely end effector of these three structures is MPT pore. Alternatively, it is possible, that unique molecular complex appearing a single end effector of postconditioning does not exist. Perhaps, that there are several effectors ensured cardioprotective effect of an adaptive phenomenon of postconditioning. PMID:26470485

  16. [Microvolt T-wave alternans. Ischemic vs. nonischemic dilated cardiomyopathy].

    PubMed

    Klingenheben, Thomas

    2015-03-01

    The use of implantable cardioverter defibrillators (ICD) for primary preventive therapy of sudden arrhythmogenic death has become a mainstay in selected patients with systolic congestive heart failure, particularly in the setting of ischemic and nonischemic cardiomyopathy (Moss et al., N Engl J Med 346:877–883, 2002; Bardy et al., N Engl J Med 352:225–237, 2005). However, more accurate identification of high-risk patients is desirable in order to avoid unnecessary ICD implants. Since currently available risk stratification methods have limited predictive accuracy, development of new techniques is important in order to noninvasively assess arrhythmogenic risk in patients prone to sudden death.Microvolt level T-wave alternans (mTWA) has recently been proposed to assess abnormalities in ventricular repolarization favoring the occurrence of reentrant arrhythmias (Adam et al., J Electrocardiol 17:209–218, 1984; Pastore et al., Circulation 99:1385–1394, 1999). In 1994, a preliminary clinical study by Rosenbaum et al. convincingly demonstrated that mTWA is closely related to arrhythmia induction in the electrophysiology laboratory as well as to the occurrence of spontaneous ventricular tachyarrhythmias during follow-up (Rosenbaum et al., N Engl J Med 330:235–241,1994). More recently, a number of clinical studies have examined its clinical applicability in ischemic and nonischemic cardiomyopathy. PMID:25693483

  17. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials

    PubMed Central

    Liu, Jialing; Wang, Yongting; Akamatsu, Yosuke; Lee, Chih Cheng; Stetler, R Anne; Lawton, Michael T.; Yang, Guo-Yuan

    2014-01-01

    The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke. PMID:24291532

  18. Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis

    PubMed Central

    Low, Audrey S. L.; Lunt, Mark; Mercer, Louise K.; Watson, Kath D.; Dixon, William G.; Symmons, Deborah P. M.

    2016-01-01

    Objective Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30‐day and 1‐year mortality after ischemic stroke. Methods Patients with RA starting therapy with TNFi and a biologics‐naive comparator group treated with synthetic disease‐modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever‐exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD–treated patients and TNFi‐treated patients using logistic regression, adjusted for age and sex. Results To April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD–treated patients and 106 in 11,642 TNFi‐treated patients) occurred during 11,973 and 61,226 person‐years of observation, respectively (incidence rate 175 versus 173 per 100,000 person‐years). After adjustment for confounders, there was no association between ever‐exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54–1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03–1.21] and 0.60 [95

  19. Delayed Remote Ischemic Postconditioning Improves Long Term Sensory Motor Deficits in a Neonatal Hypoxic Ischemic Rat Model

    PubMed Central

    Tang, Junjia; Li, Li; Barnhart, Margaret; Doycheva, Desislava M.; Zhang, John H.; Tang, Jiping

    2014-01-01

    Objective Remote Ischemic Postconditioning (RIPC) is a promising therapeutic intervention wherein a sub-lethal ischemic insult induced in one organ (limb) improves ischemia in an organ distant to it (brain). The main objective of this study was to investigate the long-term functional effects of delayed RIPC in a neonatal hypoxia-ischemia (HI) rat model. Method 10 day old rat pups were subjected to delayed RIPC treatment and randomized into four groups: 1) Sham, 2) HI induced, 3) HI +24 hr delayed RIPC, and 4) HI +24 hr delayed RIPC with three consecutive daily treatments. Neurobehavioral tests, brain weights, gross and microscopic brain tissue morphologies, and systemic organ weights were evaluated at five weeks post surgery. Results HI induced rats performed significantly worse than sham but both groups of delayed RIPC treatment showed improvement of sensory motor functions. Furthermore, compared to the HI induced group, the delayed RIPC treatment groups showed no further detrimental changes on brain tissue, both grossly and morphologically, and no changes on the systemic organ weights. Conclusion Delayed RIPC significantly improves long term sensory motor deficits in a neonatal HI rat model. A 24 hr delayed treatment does not significantly attenuate morphological brain injury but does attenuate sensory motor deficits. Sensory motor deficits improve with both a single treatment and with three consecutive daily treatments, and the consecutive treatments are possibly being more beneficial. PMID:24587303

  20. Ambient air pollution and risk of ischemic stroke and TIA

    PubMed Central

    Lisabeth, LD; Escobar, JD; Dvonch, JT; Sanchez, BN; Majersik, JJ; Brown, DL; Smith, MA; Morgenstern, LB

    2009-01-01

    Background Data on the association between air pollution and cerebrovascular disease in the US are limited. The objective of this study was to investigate the association between short-term exposure to ambient air pollution and risk of ischemic cerebrovascular events in a US community. Methods Daily counts of ischemic strokes/TIAs (2001–2005) were obtained from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) Project. Daily particulate matter <2.5μm in diameter (PM2.5), ozone (O3), and meteorological data were obtained from Texas Commission on Environmental Quality. To examine the association between PM2.5 and stroke/TIA risk, Poisson regression was used. Separate models included same day PM2.5, PM2.5 lagged 1–5 days, and an averaged lag effect. All models were adjusted for temperature, day of week and temporal trends in stroke/TIA. The effects of O3 were also investigated. Results Median PM2.5 was 7.0 μg/m3 (Inter Quartile Range (IQR): 4.8–10.0). There were borderline significant associations between same day (RR=1.03, 95% CI:0.99–1.07 for an IQR increase in PM2.5) and previous day (RR=1.03, 95% CI:1.00–1.07) PM2.5 and stroke/TIA risk. These associations were independent of O3, which demonstrated similar associations with stroke/TIA risk (same day RR=1.02, 95% CI: 0.97–1.08 and previous day RR=1.04, 95% CI: 0.99–1.09) in two pollutant models. Inference We observed associations between recent PM2.5 and O3 exposure and ischemic stroke/TIA risk even in this community with relatively low pollutant levels. This study provides data on environmental exposures and stroke risk in the US and suggests future research on ambient air pollution and stroke is warranted. PMID:18508356

  1. Mean platelet volume is related with ischemic stroke in patients with sinus rhythm.

    PubMed

    Özkan, Buğra; Arik, Osman Z; Gözükara, Mehmet Y; Şahin, Durmuş Y; Topal, Salih; Uysal, Onur K; Elbasan, Zafer; Epçeliden, Tuncay; Çayli, Murat; Gür, Mustafa

    2016-07-01

    Stroke is the leading cause of disability worldwide. It is known that atrial fibrillation and left atrial enlargement contribute ischemic stroke, and mean platelet volume (MPV) increases in patients with ischemic stroke and atrial fibrillation. We aimed to determine whether higher MPV is associated with ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched healthy individuals as control group (Group 2). After physical and echocardiographic examination, 24-48 h Holter monitoring and complete blood counts were studied. There were no statistically significant differences in age, sex rates, and comorbidities between groups. Left atrial diameter was higher in Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was significantly higher in Group 1 (P < 0.001) and was an independent determinant [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In conclusion, higher MPV is associated with acute ischemic stroke in patients with sinus rhythm and without heart failure or left atrial enlargement. MPV and left atrial diameter are independent predictors of ischemic stroke in this patient population. PMID:24686100

  2. Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target

    PubMed Central

    Jin, Zhen; Wu, Jinzi; Yan, Liang-Jun

    2016-01-01

    It is well established that the brain can be prepared to resist or tolerate ischemic stroke injury, and mitochondrion is a major target for this tolerance. The preparation of ischemic stroke tolerance can be achieved by three major approaches: ischemic conditioning, hypoxic conditioning and chemical conditioning. In each conditioning approach, there are often two strategies that can be used to achieve the conditioning effects, namely preconditioning (Pre-C) and postconditioning (Post-C). In this review, we focus on chemical conditioning of mitochondrial proteins as targets for neuroprotection against ischemic stroke injury. Mitochondrial targets covered include complexes I, II, IV, the ATP-sensitive potassium channel (mitoKATP), adenine dinucleotide translocase (ANT) and the mitochondrial permeability transition pore (mPTP). While numerous mitochondrial proteins have not been evaluated in the context of chemical conditioning and ischemic stroke tolerance, the paradigms and approaches reviewed in this article should provide general guidelines on testing those mitochondrial components that have not been investigated. A deep understanding of mitochondria as the target of chemical conditioning for ischemic stroke tolerance should provide valuable insights into strategies for fighting ischemic stroke, a leading cause of death in the world. PMID:27005615

  3. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke.

    PubMed

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood-brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  4. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke

    PubMed Central

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  5. Hypoxia Inducible Factor 1 as a Therapeutic Target in Ischemic Stroke

    PubMed Central

    Shi, H

    2010-01-01

    In stroke research, a significant focus is to develop therapeutic strategies that prevent neuronal death and improve recovery. Yet, few successful therapeutic strategies have emerged. Hypoxia-inducible factor 1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be an important player in neurological outcomes following ischemic stroke due to the functions of its downstream genes. These include genes that promote glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Many lines of evidence have shown that HIF-1 is induced in ischemic brains. Importantly, it seems that HIF-1 is primarily induced in the salvageable tissue of an ischemic brain, penumbra. However, the effect of HIF-1 on neuronal tissue injuries is still debatable based on evidence from in vitro and preclinical studies. Furthermore, it is of importance to understand the mechanism of HIF-1 degradation after its induction in ischemic brain. This review provides a present understanding of the mechanism of HIF-1 induction in ischemic neurons and the potential effect of HIF-1 on ischemic brain tissue. The author also elaborates on potential therapeutic approaches through understanding of the induction mechanism and of the potential role of HIF-1 in ischemic stroke. PMID:19903149

  6. Systemic Evaluation of Electrical Stimulation for Ischemic Wound Therapy in a Preclinical In Vivo Model

    PubMed Central

    Graebert, Jennifer K.; Henzel, M. Kristi; Honda, Kord S.; Bogie, Kath M.

    2014-01-01

    Objective: In a systematic preclinical investigation of ischemic wound healing, we investigated the hypothesis that electrical stimulation (ES) promotes the healing of ischemic wounds. Approach: The effects of varying clinically relevant ES variables were evaluated using our modified version of the Gould F344 rat ischemic wound model. Stimulation was delivered using the novel lightweight integrated, single-channel, current-controlled modular surface stimulation (MSS) device. Stepwise variation allowed the effects of five different stimulation paradigms within an appropriate current density range to be studied. Within each group, 8–10 animals were treated for 28 days or until the ischemic wounds were healed and 5 animals were treated for 12 days. Eight rats received sham devices. A quantitative multivariable outcomes assessment procedure was used to evaluate the effects of ES. Results: Ischemic wounds treated with a decreased interpulse interval (IPI) had the highest rate of complete wound closure at 3 weeks. Wounds treated with decreased pulse amplitude (PA) had a lower proportion of closed wounds than sham ischemic wounds and showed sustained inflammation with a lack of wound contraction. Innovation: Our systematic study of varying ES paradigms using the novel MSS device provides preliminary insight into potential mechanisms of ES in ischemic wound healing. Conclusion: Clinically appropriate ES can more than double the proportion of ischemic wounds closed by 3 weeks in this model. Ninety percent of wounds treated with a decreased IPI healed by 21 days compared with only 29% of ischemic wounds treated with decreased PA, which appears to inhibit healing. PMID:24940557

  7. Systemic Evaluation of Electrical Stimulation for Ischemic Wound Therapy in a Preclinical In Vivo Model.

    PubMed

    Graebert, Jennifer K; Henzel, M Kristi; Honda, Kord S; Bogie, Kath M

    2014-06-01

    Objective: In a systematic preclinical investigation of ischemic wound healing, we investigated the hypothesis that electrical stimulation (ES) promotes the healing of ischemic wounds. Approach: The effects of varying clinically relevant ES variables were evaluated using our modified version of the Gould F344 rat ischemic wound model. Stimulation was delivered using the novel lightweight integrated, single-channel, current-controlled modular surface stimulation (MSS) device. Stepwise variation allowed the effects of five different stimulation paradigms within an appropriate current density range to be studied. Within each group, 8-10 animals were treated for 28 days or until the ischemic wounds were healed and 5 animals were treated for 12 days. Eight rats received sham devices. A quantitative multivariable outcomes assessment procedure was used to evaluate the effects of ES. Results: Ischemic wounds treated with a decreased interpulse interval (IPI) had the highest rate of complete wound closure at 3 weeks. Wounds treated with decreased pulse amplitude (PA) had a lower proportion of closed wounds than sham ischemic wounds and showed sustained inflammation with a lack of wound contraction. Innovation: Our systematic study of varying ES paradigms using the novel MSS device provides preliminary insight into potential mechanisms of ES in ischemic wound healing. Conclusion: Clinically appropriate ES can more than double the proportion of ischemic wounds closed by 3 weeks in this model. Ninety percent of wounds treated with a decreased IPI healed by 21 days compared with only 29% of ischemic wounds treated with decreased PA, which appears to inhibit healing. PMID:24940557

  8. Contributing Mechanisms of Aortic Atheroma in Ischemic Cerebrovascular Disease.

    PubMed

    Kong, Qi; Ma, Xin

    2015-12-01

    In recent years, the correlation between aortic atheroma (AA) and the occurrence and recurrence of ischemic cerebrovascular disease (ICVD) has attracted much attention, but the contributory mechanisms remain controversial. This review analyzes related research on the roles of AA in ICVD, and demonstrates the correlation between the formation and development of AA and abnormal metabolism, inflammation, hemodynamic changes, and other contributory factors. The presence of complex aortic plaque (CAP) in the ascending aorta and aortic arch increases the risk of cerebral embolism and degree of injury, while the association between CAP in the descending aorta and cerebral embolism remains ambiguous. AA also functions as an indicator of atherosclerosis burden as well as hypercoagulability, which may further increase the risk of ICVD. Further study on the relationship of AA to ICVD will improve diagnosis and treatment in clinical practice. PMID:26522269

  9. Ischemic placental syndrome - prediction and new disease monitoring.

    PubMed

    Kwiatkowski, Sebastian; Kwiatkowska, Ewa; Rzepka, Rafał; Torbe, Andrzej; Dolegowska, Barbara

    2016-06-01

    The last decade has seen an improved understanding of the cause of the development of pathologies such as gestational hypertension, preeclampsia, intrauterine growth restriction, intrauterine fetal death or placental abruption. Nowadays, we know that most conditions within this group share the same pathogenesis, the cause of which is placental ischemia. The following review is an attempt to propose a new method for prediction, diagnosis and - above all - appropriate monitoring of pregnant women and fetuses developing the ischemic placental syndrome with the use of tests that are new but yet widely available in clinical diagnosis. They are closely related to the condition's pathogenesis, therefore their elevated levels may predate clinical symptoms, and - most importantly - they correlate with syndrome aggravation and the occurrence of complications. Perhaps, the new look will allow us to improve perinatal results by reducing mortality and severe complications in pregnant women and fetal deaths resulting from sudden intrauterine fetal death or placental abruption. PMID:26444581

  10. Timing of blood pressure lowering in acute ischemic stroke.

    PubMed

    Carcel, Cheryl; Anderson, Craig S

    2015-08-01

    Whether there are any benefits without harm from early lowering of blood pressure (BP) in the setting of acute ischemic stroke (AIS) has been a longstanding controversy in medicine. Whilst most studies have consistently shown associations between elevated BP, particularly systolic BP, and poor outcome, some also report that very low BP (systolic <130 mmHg) and large reductions in systolic BP are associated with poor outcomes in AIS. However, despite these associations, the observed U- or J-shaped relationship between BP and outcome in these patients may not be causally related. Patients with more severe strokes may have a more prominent autonomic response and later lower BP as their condition worsens, often pre-terminally. Fortunately, substantial progress has been made in recent years with new evidence arising from well-conducted randomized trials. This review outlines new evidence and recommendations for clinical practice over BP management in AIS. PMID:26041479

  11. [The neurovascular unit in health and ischemic stroke].

    PubMed

    Ago, Tetsuro

    2016-04-01

    The neurovascular unit (NVU), a minimal unit to exert neurological functions, is composed of neurons, astrocytes, endothelial cells, pericytes, and extracellular matrix proteins forming basal membranes. The cell components interact with one another and function cooperatively under both physiological and pathological conditions. Pericytes and astrocytes participate crucially in the formation and maintenance of the blood-brain barrier (BBB), the tight junction formed by endothelial cells, and regulate cerebral blood flow in response to neurological activities. The BBB actively regulate molecular import and export. The concept of the NVU is also useful for understanding pathogenesis and exploring therapeutic targets in various CNS disorders. In this review, recent research advances regarding the NVU and its components in health and ischemic stroke are summarized. PMID:27333744

  12. One minute oxygen uptake in peripheral ischemic vascular disease.

    PubMed Central

    Auchincloss, J H; Meade, J W; Gilbert, R; Chamberlain, B E

    1980-01-01

    Six males, ages 31-58, with ischemic vascular disease of the lower extremities, underwent treadmill testing with measurement of oxygen uptake at 45-60 seconds of exercise (VO2-45-60) as the test score. Tests were performed at 41, 123 and 164 watts of power against gravity. Depressed values were found in five subjects with aortic, iliac or common femoral disease but normal values in a subject with narrowing of the left superficial femoral artery. Reconstructive surgery resulted in normal values in four subjects retested. In three of these a calculation was made of the increased volume of oxygen uptake during the first minute of exercise associated with postsurgical improvement. The average was 430 ml, a value high enough to suggest increased aerobic metabolism of exercising muscles. PMID:7362287

  13. Arterial Ischemic Stroke in Children: Risk Factors and Etiologies

    PubMed Central

    Numis, Adam L.

    2014-01-01

    Stroke is increasingly recognized as a significant cause of morbidity or mortality in children and as a financial burden for families and society. Recent studies have identified and confirmed presumptive risk factors and have identified novel associations with childhood arterial ischemic stroke. A better understanding of these risk factors for stroke in children, which differ from the atherosclerotic risk factors in adults, is the first step needed to improve strategies for stroke prevention and intervention and ultimately minimize the physical, mental and financial burden of AIS. Here, we discuss recent advances in research for selected childhood stroke risk factors, highlighting the progress made in our understanding of etiologic mechanisms and pathophysiology, and address the future directions for acute and long-term treatment strategies for pediatric stroke. PMID:24384876

  14. Physical exercise training and neurovascular unit in ischemic stroke.

    PubMed

    Wang, X; Zhang, M; Feng, R; Li, W B; Ren, S Q; Zhang, J; Zhang, F

    2014-06-20

    Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. In this review, we summarized the protective effects of physical exercise on neurovascular unit (NVU), including neurons, astrocytes, pericytes and the extracellular matrix. Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke. PMID:24780769

  15. Diagnosis and acute management of perinatal arterial ischemic stroke

    PubMed Central

    Ferriero, Donna M.

    2014-01-01

    Summary Perinatal arterial ischemic stroke (PAIS) can be an unrecognized cause of short- and long-term neurologic disability. Focal clonic seizure in the newborn period is the most common clinical presentation of PAIS. MRI is optimal in diagnosing PAIS; negative cranial ultrasound or CT does not rule out PAIS. Given the low rate of recurrence in combination with risk factors thought to be isolated to the maternal-fetal unit, anticoagulation or antiplatelet treatment is usually not recommended. The majority of newborns with PAIS do not go on to develop epilepsy, although further research is warranted in this area. Long-term morbidity, including motor, cognitive, and behavioral disabilities, can follow PAIS, necessitating early recognition, diagnosis, and therapy initiation. PMID:25317375

  16. Ischemic and hemorrhagic brain stem lesions mimicking diabetic ophthalmoplegia.

    PubMed

    Fujioka, T; Segawa, F; Ogawa, K; Kurihara, T; Kinoshita, M

    1995-05-01

    Two patients with diabetes mellitus, one of them with an isolated third cranial nerve palsy and the other with an isolated sixth cranial nerve palsy, are presented. MRI investigations including diffusion-weighted MRI revealed a small ischemic brain stem lesion in the former and a small hemorrhagic brain stem lesion in the latter. In the former case wallerian degeneration of the nerve fascicle within the mesencephalon was also detected. These cases indicate that vascular accidents of the brain stem may masquerade as fascicular or infranuclear disturbance of the oculomotor or abducens nerve; therefore, it is important to include brain stem lesions into the differential diagnosis of isolated ophthalmoplegia. Thorough investigation by MRI including diffusion-weighted MRI is helpful for correct diagnosis. PMID:7656493

  17. Ischemic steal syndrome following arm arteriovenous fistula for hemodialysis.

    PubMed

    Zamani, Payman; Kaufman, James; Kinlay, Scott

    2009-11-01

    Arteriovenous fistulae in the arm are commonly used for hemodialysis in end-stage renal disease. Although physiological steal with reverse flow in the artery distal to the fistula is common, hand ischemia or infarction are rare. The ischemic steal syndrome (hand or forearm ischemia) is usually a result of arterial disease proximal or distal to the fistula and/or poor collateral supply to the hand. The diagnosis is primarily clinical; however, markedly reduced digital pressures and pulse volume recordings support the diagnosis. Management requires imaging for focal stenoses or disease in arteries proximal and distal to the fistula from the aorta to the hand. We present a case caused by subclavian artery occlusion that was initially missed due to focusing investigation only on the fistula. We describe the percutaneous treatments and surgical revisions that attempt to restore flow to the hand without compromising the fistula. PMID:19808723

  18. Ischemic Stroke in Confederation with Trivial Head Trauma

    PubMed Central

    Shegji, Vijaykumar

    2016-01-01

    Minor head injuries in children are common, resulting in brain concussion, and these injuries mostly end up without complications. Usually head trauma results in hemorrhagic stroke. Here we present a case of ischemic stroke following a trivial head trauma. A 10-month-old girl presented with posttraumatic right sided hemiparesis with right sided facial palsy. MRI brain revealed an area of acute infarct in the left capsuloganglionic region. The child was initially managed conservatively, as the hematological parameters were normal, and was started on anticoagulant therapy. An improvement in the clinical condition was achieved in 12 hrs of treatment with gain in power and resolution of weakness in 10 days. The specific cause for hemiparesis in the child is not elicited; possibility of genetic and environmental factors can be attributable. PMID:27313936

  19. Reparative resynchronization in ischemic heart failure: an emerging strategy

    PubMed Central

    Yamada, Satsuki; Terzic, Andre

    2014-01-01

    Cardiac dyssynchrony refers to disparity in cardiac wall motion, a serious consequence of myocardial infarction associated with poor outcome. Infarct-induced scar is refractory to device-based cardiac resynchronization therapy, which relies on viable tissue. Leveraging the prospect of structural and functional regeneration, reparative resynchronization has emerged as a potentially achievable strategy. In proof-of-concept studies, stem-cell therapy eliminates contractile deficit originating from infarcted regions and secures long-term synchronization with tissue repair. Limited clinical experience suggests benefit of cell interventions in acute and chronic ischemic heart disease as adjuvant to standard of care. A regenerative resynchronization option for dyssynchronous heart failure thus merits validation. PMID:24840208

  20. Antiphospholipid Syndrome and Vascular Ischemic (Occlusive) Diseases: An Overview

    PubMed Central

    2007-01-01

    Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/venous thrombotic events, (ii) psychiatric features and (iii) other non-thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management. PMID:18159581

  1. Imaging Systemic Inflammatory Networks in Ischemic Heart Disease

    PubMed Central

    Nahrendorf, Matthias; Frantz, Stefan; Swirski, Filip K.; Mulder, Willem J.M.; Randolph, Gwendalyn; Ertl, Georg; Ntziachristos, Vasilis; Piek, Jan; Stroes, Erik; Schwaiger, Markus; Mann, Douglas L.; Fayad, Zahi A.

    2015-01-01

    While acute myocardial infarction mortality declines, patients continue to face reinfarction and/or heart failure. The immune system, which intimately interacts with healthy and diseased tissues through resident and recruited leukocytes, is a central interface for a global host response to ischemia. Pathways that enhance the systemic leukocyte supply may be potential therapeutic targets. Pre-clinically, imaging helps identify immunity’s decision nodes, which may serve as such targets. In translating the rapidly expanding preclinical data on immune activity, the difficulty of obtaining multiple clinical tissue samples from involved organs is an obstacle that whole-body imaging can help overcome. In patients, molecular and cellular imaging can be integrated with blood-based diagnostics to assess the translatability of discoveries, including the activation of hematopoietic tissues after myocardial infarction, and serve as an endpoint in clinical trials. In this review, we discuss these concepts while focusing on imaging immune activity in organs involved in ischemic heart disease. PMID:25881940

  2. Imaging of occlusive thrombi in acute ischemic stroke

    PubMed Central

    Gasparian, GG; Sanossian, N; Shiroishi, MS; Liebeskind, DS

    2015-01-01

    Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal CT and MRI, angiography and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management. PMID:25545291

  3. Targeted Delivery of Nanoparticles to Ischemic Muscle for Imaging and Therapeutic Angiogenesis

    PubMed Central

    Kim, Jaeyun; Cao, Lan; Shvartsman, Dmitry; Silva, Eduardo A.; Mooney, David J.

    2010-01-01

    Targeting of nanoparticles to ischemic tissues was studied in a murine ischemic hindlimb model. Intravenously injected fluorescent nanoparticles allowed ischemia-targeted imaging of ischemic muscles due to increased permeability of blood vessels in hypoxic tissues. Targeting efficiency correlated with blood perfusion after induction of ischemia and was enhanced in early stage of ischemia (<7 days). Therapeutic delivery of vascular endothelial growth factor (VEGF) was achieved by VEGF-conjugated nanoparticles and resulted in a 1.7-fold increase in blood perfusion, as compared to control mice. This work supports the application of nanoparticles as imaging and therapeutic modalities for ischemia treatment. PMID:21192718

  4. [NDT-Bobath method used in the rehabilitation of patients with a history of ischemic stroke].

    PubMed

    Klimkiewicz, Paulina; Kubsik, Anna; Woldańska-Okońska, Marta

    2012-01-01

    Ischemic stroke is the third leading cause of death and disability in human. The vitally important problem after ischemic stroke is hemiparesis of the body. The most common methods used in improving the mobility of patients after ischemic stroke is a Bobath-NDT (Neuro-Developmental Treatment - Bobath), which initiated the Berta and Karel Bobath for children with cerebral palsy. It is a method designed to neurophysiological recovery of these vital functions that the patient was lost due to illness, and wants it back. PMID:23289255

  5. Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke

    PubMed Central

    Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra

    2013-01-01

    Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917

  6. Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke.

    PubMed

    Mehrpour, Masoud; Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra

    2013-01-01

    Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917

  7. Effect and Safety of Rosuvastatin in Acute Ischemic Stroke

    PubMed Central

    Heo, Ji Hoe; Song, Dongbeom; Nam, Hyo Suk; Kim, Eung Yeop; Kim, Young Dae; Lee, Kyung-Yul; Lee, Ki-Jeong; Yoo, Joonsang; Kim, Youn Nam; Lee, Byung Chul; Yoon, Byung-Woo; Kim, Jong S.

    2016-01-01

    Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation. PMID:26846760

  8. Myocardial ischemic reperfusion induces de novo Nrf2 protein translation

    PubMed Central

    Xu, Beibei; Zhang, Jack; Strom, Joshua; Lee, Sang; Chen, Qin M.

    2016-01-01

    Nrf2 is a bZIP transcription factor regulating the expression of antioxidant and detoxification genes. We have found that Nrf2 knockout mice have an increased infarction size in response to regional ischemic reperfusion and have a reduced degree of cardiac protection by means of ischemic preconditioning. With cycles of brief ischemia and reperfusion (5′I/5′R) that induce cardiac protection in wild type mice, an elevated Nrf2 protein was observed without prior increases of Nrf2 mRNA. When an mRNA species is being translated into a protein, it is occupied by multiple ribosomes. The level of ribosome-associated Nrf2 mRNA increased following cycles of 5′I/5′R, supporting de novo Nrf2 protein translation. A dicistronic reporter assay indicated a role of the 5′ untranslated region (5′ UTR) of Nrf2 mRNA in oxidative stress induced Nrf2 protein translation in isolated cardiomyocytes. Western blot analyses after isolation of proteins binding to biotinylated Nrf2 5′ UTR from the myocardium or cultured cardiomyocytes demonstrated that cycles of 5′I/5′R or oxidants caused an increased association of La protein with Nrf2 5′ UTR. Ribonucleoprotein complex immunoprecipitation assays confirmed such association indeed occurring in vivo. Knocking down La using siRNA was able to prevent Nrf2 protein elevation by oxidants in cultured cardiomyocytes and by cycles of 5′I/5′R in the myocardium. Our data point out a novel mechanism of cardiac protection by de novo Nrf2 protein translation involving interaction of La protein with 5′ UTR of Nrf2 mRNA in cardiomyocytes. PMID:24915518

  9. Buyanghuanwu Tang therapy for neonatal rats with hypoxic ischemic encephalopathy

    PubMed Central

    Liu, Xiyao; Min, Yue; Gu, Weiwang; Wang, Yujue; Tian, Yuguang

    2015-01-01

    Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a clinical syndrome manifested by neurological symptoms in the first days of life in term infants. Purpose: To investigate the therapy effect of Buyanghuanwu Tang (BYHWT), a decoction with 7 herbal ingredients, on neonatal rats with hypoxic ischemic encephalopathy (HIE) and its mechanism. Methods: 50 3-week male Sprague-Dawley rats were divided into normal control group, model group, BYHWT 1d group, BYHWT 3d group and BYHWT 7d group, 10 rats in each group. The HIE model of was established in later 4 groups. The later 3 groups were treated with BYHWT for 1, 3 and 7 days, respectively, and the normal control group and model group were treated with PBS. The Morris water maze test and dynamic 18F-FDG-PET/CT imaging were performed. The changes of hippocampal tissue observed by histopathologic examination, and the expressions of JNK1/JNK2 and TNF-α protein were observed western blotting. Results: Compared with model group, the impaired performance on distance and latency parameters was mitigated in BYHWT 1d group, BYHWT 3d group and BYHWT 7d group (P < 0.01), the FDG uptake was decreased in BYHWT 3d group and BYHWT 7d group, the apoptotic cells and inflammatory cells were significantly decreased in BYHWT 3d group and BYHWT 7d group, and the expressions of JNK1/JNK2 and TNF-α protein were significantly decreased in BYHWT 7d group (P < 0.05). Conclusion: BYHWT can delay the HIE onset and preserve the motor function, primarily by regulating inflammation, apoptosis and inhibition by mediating JNK signaling. PMID:26770451

  10. MicroRNA Dysregulation in Diabetic Ischemic Heart Failure Patients

    PubMed Central

    Greco, Simona; Fasanaro, Pasquale; Castelvecchio, Serenella; D’Alessandra, Yuri; Arcelli, Diego; Di Donato, Marisa; Malavazos, Alexis; Capogrossi, Maurizio C.; Menicanti, Lorenzo; Martelli, Fabio

    2012-01-01

    Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients. PMID:22427379

  11. Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

    PubMed Central

    Geer, J. C.; Crago, C. A.; Little, W. C.; Gardner, L. L.; Bishop, S. P.

    1980-01-01

    Morphologic changes in the subendocardial myocardium that appeared to be caused by severe, chronic subendocardial ischemia were studied in patients with fatal ischemic heart disease admitted to the Specialized Center of Research for Ischemic Heart Disease at the University of Alabama in Birmingham in the period 1970--1977. Thirteen patients were selected for this report on the basis that they had the lesions in the subendocardial myocardium we believe to have been caused by subendocardial ischemia and had no evidence of acute or remote myocardial infarction or other conditions that may have contributed to their terminal illness or death. Clinical findings were unstable angina, congestive heart failure, usually no increase in plasma enzymes indicative of myocardial damage, and electrocardiographic changes consistent with subendocardial ischemia. All 13 patients had 75% or greater stenosis of the three major coronary arteries; none had acute thrombotic or embolic coronary artery occlusion. The left ventricle in all cases was hypertrophied. The subendocardial myocardium showed circumferential pallor, hyperemia, or focal fibrosis without perceptible loss of volume in papillary muscles or trabeculae carneae. Microscopically, acute lesions showed one to two layers of preserved myofibers adjacent to the endocardium, vacuolar change in the deeper fibers, and focal areas of coagulation necrosis of variable size in the myocardium external to the fibers with vacuolar change. Coagulation necrosis was extensive in some cases and usually was not associated with infiltration of neutrophils. The repair reaction involved removal of necrotic sarcoplasm by mononuclear phagocytes, resulting in a reticular-appearing tissue without evidence of stromal collapse. Granulation tissue was not seen. Collagen fibers appeared to be deposited within the area of previous sarcolemmal sheaths. The distribution and morphology of subendocardial myocardial lesions associated with severe coronary

  12. Neurotoxic lipid peroxidation species formed by ischemic stroke increase injury

    PubMed Central

    Zeiger, Stephanie L. H.; Musiek, Erik S.; Zanoni, Giuseppe; Vidari, Giovanni; Morrow, Jason D.; Milne, Ginger J.; McLaughlin, BethAnn

    2009-01-01

    Stroke is the third leading cause of death in the United States yet no neuroprotective agents for treatment are clinically available. There is a pressing need to understand the signaling molecules which mediate ischemic cell death and identify novel neuroprotective targets. Cyclopentenone isoprostanes (IsoP), formed following free radical mediated peroxidation of arachidonic acid, are used as markers of stress but their bioactivity is poorly understood. We have recently shown that 15-A2t-Isop is a potent neurotoxin in vitro and increases the free radical burden in neurons. In this work, we demonstrate that 15-A2t-IsoP is abundantly produced in stroke infarcted human cortical tissue. Using primary neuronal cultures we found that minimally toxic exposure to 15-A2t-IsoP does not alter ATP content, but in combination with oxygen glucose deprivation resulted in a significant hyperpolarization of the mitochondrial membrane and dramatically increased neuronal cell death. In the presence of Ca2+, 15-A2t-IsoP led to a rapid induction of the permeability transition pore and release of cytochrome c. Taken with our previous work, these data support a model in which ischemia causes generation of reactive oxygen species, calcium influx, lipid peroxidation and 15-A2t-IsoP formation. These factors combine to enhance opening of the permeability transition pore leading to cell death subsequent to mitochondrial cytochrome c release. This data is the first documentation of significant 15-A2t-IsoP formation following acute ischemic stroke and suggests addition of 15-A2t-IsoP to in vitro models of ischemia may help to more fully recapitulate stroke injury. PMID:19699297

  13. Hypertension and ischemic heart disease. Role of dipyridamole echocardiography test.

    PubMed

    Gulizia, M M; Lo Giudice, P; Doria, G; Valenti, R; Circo, A G

    1994-11-01

    The aim of this study is to try to evaluate the relationship between arterial hypertension and ischemic heart disease (IHD) in the light of the physiopathologic response pattern to the dipyridamole echocardiography test (DET) in hypertensive patients, in pharmacologic washout, without any electrocardiographic ST segment depression during exercise tests or at rest. Sixty patients affected by mild to moderate asymptomatic essential arterial hypertension were studied: the subjects had a sitting diastolic blood pressure > or = 95 < or = 114 mmHg; there were 38 men and 22 women with a mean age of 49.8 +/- 7.6 years (range twenty-nine to sixty-eight). All patients had undergone high-dose DET (0.84 mg/kg in ten minutes). No patients developed side effects or asynergy in cardiac contractility during the test. In the absence of any significant coronary artery obstruction assessed angiographically, 18 patients (30%) showed ST segment depression > 1.0 mV during DET, sometimes with the presence of ventricular and/or supraventricular extrasystoles. In this group of patients the left ventricular mass index (LVMI) and duration of hypertension (in months) were higher as compared with those of the other 42 patients (respectively: 160.2 +/- 5.1 vs 129.2 +/- 9.2 g/m2, P < 0.02; and 30 +/- 4.8 vs 9 +/- 5.4 months, P < 0.007). In conclusion it is reasonable to speculate from these data that the ischemic-like" dipyridamole-induced ST segment depression, like that shown by patients affected by Syndrome X, might involve a worse prognosis in hypertensive patients. This may be because of increased coronary resistance due to structural modification or anatomic background. PMID:7978508

  14. Protective and Antioxidant Effects of PPARα in the Ischemic Retina

    PubMed Central

    Moran, Elizabeth; Ding, Lexi; Wang, Zhongxiao; Cheng, Rui; Chen, Qian; Moore, Robert; Takahashi, Yusuke; Ma, Jian-xing

    2014-01-01

    Purpose. Previous studies have demonstrated that peroxisome proliferator-activated receptor-alpha (PPARα) agonists have therapeutic effects in diabetic retinopathy, although the mechanism of action remains incompletely understood. The purpose of this study was to evaluate PPARα's protective effects in the ischemic retina, and to delineate its molecular mechanism of action. Methods. For the oxygen-induced retinopathy (OIR) model, wild-type (WT), and PPARα knockout (PPARα−/−) mice were exposed to 75% O2 from postnatal day 7 (P7) to P12 and treated with the PPARα agonist fenofibric acid (Feno-FA) from P12 to P16. At P17, the effects of Feno-FA on retinal glial fibrillary acidic protein (GFAP) expression, apoptotic DNA cleavage, and TUNEL labeling were analyzed. Cultured retinal cells were exposed to CoCl2 to induce hypoxia, and TUNEL staining and 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein dye were used to measure apoptosis and reactive oxygen species (ROS) generation. Western blotting was used to measure GFAP levels and cell signaling. Results. Feno-FA decreased retinal apoptosis and oxidative stress in WT but not PPARα−/− OIR mice. Peroxisome proliferator-activated receptor-alpha knockout OIR mice showed increased retinal cell death and glial activation in comparison to WT OIR mice. Feno-FA treatment and PPARα overexpression protected cultured retinal cells from hypoxic cell death and decreased ROS levels. Nuclear hypoxia-inducible factor-α (HIF-1α) and nicotine adenine dinucleotide phosphate oxidase-4 (Nox 4) were increased in OIR retinas and downregulated by Feno-FA in WT but not in PPARα−/− mice. Conclusions. Peroxisome proliferator-activated receptor-alpha has a potent antiapoptotic effect in the ischemic retina. This protective effect may be mediated in part through downregulation of HIF-1α/Nox 4 and consequently alleviation of oxidative stress. PMID:24825105

  15. Proton relaxation in acute and subacute ischemic brain edema

    SciTech Connect

    Boisvert, D.P.; Handa, Y.; Allen, P.S. )

    1990-01-01

    The relation between regional ischemic brain edema and tissue proton relaxation rates (R1 = 1/T1; R2 = 1/T2) were studied in 16 macaque monkeys subjected to MCA occlusion. In vivo R2 measurements were obtained from multiple spin-echo (eight echoes) images taken at 2-, 3-, 4-, and 72-hr postischemia. In vitro R1 and R2 values were determined for corresponding regions after sacrifice at 4 hr (n = 8) or at 72-hr postischemia in seven surviving animals. The water content of the white and gray matter tissue samples was measured by the wet/dry method. Four animals (25%) showed ipsilateral regions of increased signal intensity as early as 2 hr after MCA occlusion. All seven animals imaged at 72 hr displayed such regions. Despite the absence of measured changes in tissue water content, significant decreases in R2, but not in R1, occurred at 4 hr. At this stage, R2 values correlated more closely than R1 with individual variations in water content. At 72 hr, marked decreases in both R1 and R2 were measured in ischemic deep gray matter and white matter. Cortical gray matter was unchanged. In edematous gray and white matter, both R1 and R2 correlated closely with tissue water content, but R2 was consistently 10 to 20 times more sensitive than R1. Biexponential R2 decay was observed at 4 and 72 hr, but only in the white matter region that became severely edematous at 72 hr.

  16. A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

    PubMed Central

    Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

    2014-01-01

    Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

  17. Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema

    PubMed Central

    Kiire, Christine A; Morjaria, Rupal; Rudenko, Anna; Fantato, Alexina; Smith, Lewis; Smith, Amy; Chong, Victor

    2015-01-01

    Purpose Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. Methods Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 μm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. Results Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046). Conclusion In this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course. PMID:26715833

  18. Risk factors of transient ischemic attack: An overview

    PubMed Central

    Khare, Supreet

    2016-01-01

    Transient ischemic attack (TIA) is a transient episode of neurologic dysfunction caused due to loss of blood flow to the brain or spinal cord without acute infarction. Depending on the area of the brain involved, symptoms of TIA vary widely from patient to patient. Since the blockage period in TIA is very short-lived, there is no permanent damage. Risk factors for TIA include family history of stroke or TIA, age above 55 years or older, higher risk of TIA in males than females, high blood pressure, diabetes mellitus, and tobacco smoking. Genetics, race, and imbalance in lipid profile are other risk factors of TIA. TIA is usually diagnosed after taking a thorough history and a physical examination. Several radiological tests such as computed tomography and magnetic resonance imaging are useful in the evaluation of patients who have had a TIA. Ultrasound of the neck and an echocardiogram of the heart are other tests useful in the diagnosis and evaluation of the attack. The treatment following acute recovery from a TIA depends on the underlying cause. Patients who have more than 70% stenosis of the carotid artery, removal of atherosclerotic plaque is usually done by carotid endarterectomy surgery. One-third of the people with TIA can later have recurrent TIAs and one-third can have a stroke because of permanent nerve cell loss. Having a TIA is a risk factor for eventually having a stroke. Educating the patients and inculcating lifestyle modifications in them are initial steps to minimize the prevalence of transient ischemic attack. PMID:27134474

  19. Mesenchymal Stem Cells for Ischemic Stroke: Progress and Possibilities.

    PubMed

    Maria Ferri, Anna Lucia; Bersano, Anna; Lisini, Daniela; Boncoraglio, Giorgio; Frigerio, Simona; Parati, Eugenio

    2016-05-27

    Stroke is the most common neurological cause of morbidity and mortality in industrialized countries, afflicting 15 million people every year. The numbers are expected to increase, mostly due to aging populations. One in five stroke patients dies, and one in three are left with permanent disabilities. Although some acute phase therapies such as intravenous recombinant tissue plasminogen activator (rt-PA) andendovascular treatment have been shown to improve ischemic stroke outcome, these therapies are available only for a small proportion of patients. The use of stem cells to replace brain cells lost during stroke is a long-term goal, and one which is difficult to achieve given that transplanted cells must integrate and restore neural pathways to regain function of damaged parts of the brain. Over the past decade the use of mesenchymal stromal cells (MSCs) as therapy has emerged as a particularly attractive option. MSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Herein, we present a review of the application of MSCs in ischemic stroke, including the source of MSCs, the route and timing of their delivery into the brain and the endpoints measured. Experimental data of transplantation of MSCs in animal stroke models suggest an improved functional recovery. The transplantation of MSCs influences a wide range of events by modulating the inflammatory environment, stimulating endogenous neurogenesis and angiogenesis and reducing the formation of glial scar, although the precise, underlying mechanism of this phenomenon remains unknown. The results from early clinical trials highlight the need to optimize variables such as cell selection and route of administration in order to translate these results into safe and successful clinical applications. PMID:26898654

  20. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke

    PubMed Central

    Ren, Changhong; Wang, Pengcheng; Wang, Brian; Li, Ning; Li, Weiguang; Zhang, Chenggang; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Abstract Purpose: Limb remote ischemic per-conditioning or post-conditioning has been shown to be neuroprotective after cerebral ischemic stroke. However, the effect of combining remote per-conditioning with post-conditioning on ischemic/reperfusion injury as well as the underlying mechanisms are largely unexplored. Methods: Here, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was immediately applied after onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 hr after reperfusion (post-conditioning). The infarct volume, motor function, and the expression of neuroglobin (Ngb) were measured at different durations after reperfusion. Results: We found that a single episode of limb remote per-conditioning afforded short-term protection, but combining repeated remote post-conditioning during the 14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion injury. Interestingly, we also found that ischemic per- and post-conditioning significantly increased expression of Ngb, an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke, at peri-infarct regions from day 1 to day 14 following ischemia/reperfusion. Conclusion: Our results suggest that the conventional per-conditioning combined with post-conditioning may be used as a novel neuroprotective strategy against ischemia-reperfusion injury, and Ngb seems to be one of the important players in limb remote ischemia-mediated neuroprotection. PMID:25868435

  1. Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis.

    PubMed

    Wang, Wen; Zhang, Lu; Liu, Weiming; Zhu, Qin; Lan, Qing; Zhao, Jizong

    2016-05-01

    Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta-analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta-analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients. PMID:26856461

  2. Two children with both arm ischemia and arterial ischemic stroke during the perinatal period.

    PubMed

    McKasson, Marilyn J; Golomb, Meredith R

    2011-12-01

    It is rare for both limb ischemia and arterial ischemic stroke to occur in the same child during the perinatal period. Two children who appear to have had perinatal emboli to both an arm and a middle cerebral artery territory are presented here. One child required amputation of the ischemic limb below the shoulder, and the other required skin grafts to the distal ischemic fingers. Each of these children later received cerebral magnetic resonance imaging for evaluation of developmental delay and was found to have what appeared to be old perinatal arterial ischemic stroke. Both children were homozygous for the methylenetetrahydrofolate reductase C677T gene variant. Eight other children with perinatal limb ischemia and stroke were found on literature review; several also had delayed diagnosis of perinatal stroke. This report examines the approach to diagnosis and treatment in each of these and makes suggestions for the similar cases in the future. PMID:21862833

  3. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke

    PubMed Central

    Arboix, Adrià

    2015-01-01

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  4. Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in Patients with AIDS: Optical Coherence Tomography Findings.

    PubMed

    Arevalo, J Fernando; Garcia, Reinaldo A; Arevalo, Fernando A; Fernandez, Carlos F

    2015-01-01

    To describe the clinical and optical coherence tomography (OCT) characteristics of ischemic maculopathy in two patients with acquired immunodeficiency syndrome (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed ischemic maculopathy. Both patients presented with central visual loss and active granular CMV retinitis. The presence of opacification of the superficial retina in the macular area and intraretinal edema suggested the diagnosis. Fluorescein angiography changes were similar in the two cases with enlargement of the foveal avascular zone and late staining of juxtafoveal vessels. OCT changes were suggestive of retinal ischemia: Increased reflectivity from the inner retinal layer and decreased backscattering from the retinal photoreceptors due to fluid and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease in vision in AIDS patients. Fluorescein angiography and OCT should be considered in any patient with AIDS and unexplained visual loss. The mechanism of ischemic maculopathy may be multifactorial. PMID:27051496

  5. Ischemic postconditioning in cerebral ischemia: Differences between the immature and mature brain?

    PubMed

    Leger, Pierre-Louis; Bonnin, Philippe; Renolleau, Sylvain; Baud, Olivier; Charriaut-Marlangue, Christiane

    2015-10-01

    Ischemic postconditioning (postC), defined as serial mechanical interruptions of blood flow at reperfusion, effectively reduces myocardial infarct size in all species tested so far, including humans. In the brain, ischemic postC leads to controversial results regardless of variations in factors such as onset time of beginning, the duration of ischemia and/or reperfusion, and the number of cycles of occlusion/reperfusion. Thus, many major issues remain to be resolved regarding its protective effects. Future studies should aim to identify the parameters that yield the strongest protection, as well as to understand why the efficacy of ischemic postC differs between models. This review will focus on initial hemodynamic changes and their consequences, and on specific features such as NO-dependent vascular tone and/or prolonged acidosis in cerebral ischemia-reperfusion in order to better understand the dynamics of ischemic postC in the developing brain. PMID:25777940

  6. Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in Patients with AIDS: Optical Coherence Tomography Findings

    PubMed Central

    Arevalo, J. Fernando; Garcia, Reinaldo A.; Arevalo, Fernando A.; Fernandez, Carlos F.

    2015-01-01

    To describe the clinical and optical coherence tomography (OCT) characteristics of ischemic maculopathy in two patients with acquired immunodeficiency syndrome (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed ischemic maculopathy. Both patients presented with central visual loss and active granular CMV retinitis. The presence of opacification of the superficial retina in the macular area and intraretinal edema suggested the diagnosis. Fluorescein angiography changes were similar in the two cases with enlargement of the foveal avascular zone and late staining of juxtafoveal vessels. OCT changes were suggestive of retinal ischemia: Increased reflectivity from the inner retinal layer and decreased backscattering from the retinal photoreceptors due to fluid and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease in vision in AIDS patients. Fluorescein angiography and OCT should be considered in any patient with AIDS and unexplained visual loss. The mechanism of ischemic maculopathy may be multifactorial. PMID:27051496

  7. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  8. Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.

    PubMed

    Tuttolomondo, Antonino; Pecoraro, Rosaria; Arnao, Valentina; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2015-01-01

    Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies. PMID:26469760

  9. Does remote ischemic conditioning salvage left ventricular function after successful primary PCI?

    PubMed

    Hoole, Stephen P; Dutka, David P

    2011-05-01

    The translation of ischemic preconditioning to a viable therapy that benefits patients has been slow. This has been largely due to the difficultly in preempting when ischemia will occur. Recent advances in the field have demonstrated that cardioprotection from brief episodes of ischemia is possible when applied immediately after reperfusion (ischemic postconditioning) or remotely in another tissue during myocardial ischemia, prior to reperfusion (remote ischemic conditioning). This has facilitated the therapeutic application to patients presenting with acute myocardial infarction. In this article, we will discuss the results of a recent study published by Munk et al., concerning the application of remote ischemic conditioning during primary percutaneous coronary intervention to salvage myocardial function following ST-elevation myocardial infarction. PMID:21615317

  10. Surgical Management of Stuttering Ischemic Priapism: A Case Report and Concise Clinical Review.

    PubMed

    Raslan, M; Hiew, K; Hoyle, A; Ross, D G; Betts, C D; Maddineni, S B

    2016-03-01

    Stuttering priapism is an extremely rare and poorly understood entity. We present a rare case of a 47-year-old Afro-Caribbean gentleman who required proximal shunt procedure to treat his ischemic stuttering priapism after he had failed medical management. We provided a concise review of the literature on the surgical management of ischemic priapism. This case highlighted the importance of prompt surgical intervention in prolonged stuttering priapism to avoid serious psychological and functional complications. PMID:26977408

  11. Circadian rhythm of onset of stroke - in 50 cases of ischemic stroke.

    PubMed

    Uddin, M S; Hoque, M I; Uddin, M K; Kamol, S A; Chowdhury, R H

    2015-01-01

    Stroke is a leading cause of death and disability worldwide. While the immediate consequence of stroke include permanent cognitive deficits, paralysis, visual impairment and sensory disturbances; stroke also results in long term dysregulation of sleep and mood, which may be equally disabling. The influence of ischemic stroke on circadian rhythm regulation, which is strongly linked to sleep and mood, may thus potentially influence long term recovery in stroke patients. Stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. This study was done to find out the time of onset of most of the ischemic stroke attack and to determine the outcome of ischemic stroke during hospital stay. All ischemic stroke patients admitted in Medicine wards in Comilla Medical College Hospital during the period of 1st November 2010 to 30th April 2011 included in this study. After admission, a careful history and a thorough clinical examination was carried out. Data collection was done on a preset questionnaire which involved to identify the risk factors, the time of onset of ischemic stroke, and outcome during hospital stay. All the cases were investigated. Among the 50 ischemic stroke patients, 68% were male and 32% female. Maximum age groups were 61-70 years (50%). By occupational category, maximum were retired persons (46%); 68% were hypertensive, 38% smoker and 16% had diabetes. Dyslipidemia was present in 44% patients. Most of the ischemic stroke (44%) occurred in the morning to late morning (6:01AM-12:00PM) and majority (80%) of the patients was discharged with residual neurological dysfunction. This study supports the presence of a circadian pattern in the onset of ischemic stroke, with higher risk in the morning to late morning. Most of the patients were discharged with residual neurological dysfunction. PMID:25725678

  12. Application and Progress of Combined Mesenchymal Stem Cell Transplantation in the Treatment of Ischemic Cardiomyopathy

    PubMed Central

    Hua, Ping; Liu, Jian-Yang; Tao, Jun; Yang, Song-Ran

    2015-01-01

    Treatment of ischemic cardiomyopathy caused by myocardial infarction (MI) using mesenchymal stem cell (MSC) transplantation is a widely researched field, with promising clinical application. However, the low survival rate of transplanted cells has a severe impact on treatment outcome. Currently, research is focused on investigating the strategy of combining genetic engineering, tissue engineering materials, and drug/hypoxia preconditioning to improve ischemic cardiomyopathy treatment outcome using MSC transplantation treatment (MSCTT). This review discusses the application and progress of these techniques. PMID:26295041

  13. Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A

    PubMed Central

    Wei, Yanhong; Gong, Junsong; Xu, Zhenhua; Thimmulappa, Rajesh K.; Mitchell, Katherine L.; Welsbie, Derek S.; Biswal, Shyam; Duh, Elia J.

    2015-01-01

    Delayed revascularization of ischemic neural tissue is a major impediment to preservation of function in central nervous system (CNS) diseases including stroke and ischemic retinopathies. Therapeutic strategies allowing rapid revascularization are greatly needed to reduce ischemia-induced cellular damage and suppress harmful pathologic neovascularization. However, key mechanisms governing vascular recovery in ischemic CNS, including regulatory molecules governing the transition from tissue injury to tissue repair, are largely unknown. NF-E2-related factor 2 (Nrf2) is a major stress-response transcription factor well known for its cell-intrinsic cytoprotective function. However, its role in cell–cell crosstalk is less appreciated. Here we report that Nrf2 is highly activated in ischemic retina and promotes revascularization by modulating neurons in their paracrine regulation of endothelial cells. Global Nrf2 deficiency strongly suppresses retinal revascularization and increases pathologic neovascularization in a mouse model of ischemic retinopathy. Conditional knockout studies demonstrate a major role for neuronal Nrf2 in vascular regrowth into avascular retina. Deletion of neuronal Nrf2 results in semaphorin 6A (Sema6A) induction in hypoxic/ischemic retinal ganglion cells in a hypoxia-inducible factor-1 alpha (HIF-1α)-dependent fashion. Sema6A expression increases in avascular inner retina and colocalizes with Nrf2 in human fetal eyes. Extracellular Sema6A leads to dose-dependent suppression of the migratory phenotype of endothelial cells through activation of Notch signaling. Lentiviral-mediated delivery of Sema6A small hairpin RNA (shRNA) abrogates the defective retinal revascularization in Nrf2-deficient mice. Importantly, pharmacologic Nrf2 activation promotes reparative angiogenesis and suppresses pathologic neovascularization. Our findings reveal a unique function of Nrf2 in reprogramming ischemic tissue toward neurovascular repair via Sema6A regulation

  14. Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature

    NASA Astrophysics Data System (ADS)

    Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

    2013-01-01

    Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

  15. Race and sex differences in thrombogenicity: risk of ischemic events following coronary stenting.

    PubMed

    Gurbel, Paul A; Bliden, Kevin P; Cohen, Eli; Navickas, Irene A; Singla, Anand; Antonino, Mark J; Fissha, Mulugeta; Kreutz, Rolf P; Bassi, Ashwani K; Tantry, Udaya S

    2008-06-01

    Race and sex affect thrombogenicity. We have demonstrated that platelet-fibrin clot characteristics can be used to stratify patients for risk of ischemic events following percutaneous coronary intervention. We investigated race and sex differences in thrombogenicty and the relation to ischemic risk in 252 consecutive African-American and Caucasian men and women undergoing elective percutaneous coronary intervention. Platelet-fibrin clot characteristics were measured using the Thrombelastograph Hemostasis System. The incidence of adverse ischemic events was assessed over a 6-month follow-up period. Overall, 40 ischemic events (15.9%) occurred. Adverse events were higher in African-Americans than Caucasians (P = 0.14), and in women than men (P = 0.004). The incidence was highest in African-American women (37.5%) and lowest in African-American men (6.5%). Measured Thrombelastograph parameters were significantly different between ischemic and nonischemic patients (P < 0.05). African-American women in the ischemic group exhibited higher thrombogenicity than the other race and sex groups (P < 0.05). Multivariate logistic regression identified platelet-fibrin mediated clot strength (relative risk 2.52, P = 0.017) and sex (relative risk 2.56, P = 0.009) as significant independent predictors of ischemic events 6 months postpercutaneous coronary intervention. Thrombogenicity is a novel measurable cardiovascular risk factor that varies by race and sex, is highest in African-American women, and independently predicts the frequency of ischemic events following percutaneous coronary intervention. Point-of-service measurements of platelet-fibrin clot characteristics may lead to more intensified antithrombotic therapy and reduced mortality in selected patients. PMID:18469547

  16. T−786→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy

    PubMed Central

    2012-01-01

    Background Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T−786→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T−786→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy. Method A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T−786→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients. Results Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04). Conclusions T−786→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease. PMID:23031426

  17. Update on ischemic colitis: from etiopathology to treatment including patients of intensive care unit.

    PubMed

    Doulberis, Michael; Panagopoulos, Periklis; Scherz, Stephanie; Dellaporta, Erminia; Kouklakis, Georgios

    2016-08-01

    Ischemic colitis is the result of colonic hypoperfusion and is regarded as a relatively rare condition. It can be roughly classified as occlusive and non-occlusive. Pathogenesis includes a usually transient compromise in the colonic vasculature, with a parallel activation of an inflammatory cascade caused primarily by reperfusion. Diagnosis of ischemic colitis remains often difficult and requires a combination of diagnostic techniques, whereas clinical signs are occasionally only seen late as complications. Gold standard is considered to be colonoscopy. Clinical presentation and treatment of ischemic colitis vary widely depending on the degree of ischemia. Patients of intensive care unit (ICU) with ischemic colitis are often under-diagnosed, since the parallel co-morbidities and the nonspecific nature of symptoms that mimic almost any abdominal pathology, can mislead the doctor. Moreover, sedated or ventilated patients can mask many of the characteristic features of ischemic colitis and make the diagnosis challenging. Bedside colonoscopy and diagnostic laparoscopy in ICUs are two options, which seem lately to be reliable and promising in diagnosing ischemic colitis in critically ill patients. PMID:27152750

  18. Relation of Paraoxonase1, Arylesterase and Lipid Profile in Ischemic Stroke Patients

    PubMed Central

    Mogarekar, Mukund R; Wagh, Reena V; Das, Rajkumar R; Pramanik, Sanjay S; Sonune, Sanjay M; Chawhan, Sanjay M

    2015-01-01

    Background Paraoxonase 1 (PON1) is an enzyme associated with High density lipoprotein (HDL) in blood and it is considered to have antioxidant and antiatherogenic properties. PON1 plays an important role in protecting HDL and especially low density lipoprotein (LDL) from oxidative modification by hydrolyzing lipid peroxides which are known to be associated with many vascular diseases including atherosclerosis and ischemic stroke. Aim The aim of the study was to evaluate and correlate serum paraoxonase (PON1) and arylesterase (ARE) activities as well as lipid profile levels in patients with ischemic stroke. Materials and Methods The study population was comprised of 50 ischemic stroke patients and 50 healthy controls. The serum PON1 and ARE activities were measured spectrophotometrically by using paraoxon and phenylacetate as substrate respectively by Eckerson method. Serum lipid was measured using routine biochemical method. Results The normality of the distribution of the parameters are assessed by Shapiro-Wilk test. Two sample t-test is applied for hypothesis testing. The serum PONI and arylesterase ARE decreased significantly in ischemic stroke patients (p<0.001). The PON1 was positively correlated with HDL. Conclusion This study strongly suggests that the estimation of HDL-C associated PON1 enzyme gives valuable information for prediction of risk of ischemic stroke due to cerebrovascular thromboembolism. The result shows that PON1 and ARE could be considered as a risk factors for ischemic stroke. PMID:26673997

  19. Withdrawal of Antithrombotic Agents and Its Impact on Ischemic Stroke Occurrence

    PubMed Central

    Broderick, Joseph P.; Bonomo, Jordan B.; Kissela, Brett M.; Khoury, Jane C.; Moomaw, Charles J.; Alwell, Kathleen; Woo, Daniel; Flaherty, Matthew L.; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Kleindorfer, Dawn O.

    2011-01-01

    Background Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication. Methods and Results Patient records from the population-based Greater Cincinnati / Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review. Results In 2005, 2,197 cases of ischemic stroke among residents of the region were identified via hospital discharge records. Of the 2,197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal: 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes following withdrawal, 71 (62.3%) were first-ever, and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period. Conclusions The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance. PMID:21719769

  20. Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences

    PubMed Central

    Soler, Ernest Palomeras; Ruiz, Virgina Casado

    2010-01-01

    Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ischemic stroke increases the risk of suffering a coronary heart disease, and viceversa. The aim of this chapter is to review data on epidemiology, pathophisiology and risk factors for both entities, considering the differences and similarities that could be found in between them. We discuss traditional risk factors, obtained from epidemiological data, and also some novel ones, such as hyperhomocisteinemia or sleep apnea. We separate risk factors, as clasically, in two groups: nonmodifiables, which includes age, sex, or ethnicity, and modifiables, including hypertension, dyslipidemia or diabetis, in order to discuss the role of each factor in both ischemic events, ischemic stroke and coronary heart disease. PMID:21804773

  1. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  2. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    PubMed

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  3. Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis

    PubMed Central

    Duan, Bo; Wang, Yi-Zhi; Yang, Tao; Chu, Xiang-Ping; Yu, Ye; Huang, Yu; Cao, Hui; Hansen, Jillian; Simon, Roger P.; Zhu, Michael X.; Xiong, Zhi-Gang; Xu, Tian-Le

    2011-01-01

    Ischemic brain injury is a major problem associated with stroke. It has been increasingly recognized that acid-sensing ion channels (ASICs) contribute significantly to ischemic neuronal damage, but the underlying mechanism has remained elusive. Here, we show that extracellular spermine, one of the endogenous polyamines, exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Pharmacological blockade of ASIC1a or deletion of the ASIC1 gene greatly reduces the enhancing effect of spermine in ischemic neuronal damage both in cultures of dissociated neurons and in a mouse model of focal ischemia. Mechanistically, spermine profoundly reduces desensitization of ASIC1a by slowing down desensitization in the open state, shifting steady-state desensitization to more acidic pH, and accelerating recovery between repeated periods of acid stimulation. Spermine-mediated potentiation of ASIC1a activity is occluded by PcTX1 (psalmotoxin 1), a specific ASIC1a inhibitor binding to its extracellular domain. Functionally, the enhanced channel activity is accompanied by increased acid-induced neuronal membrane depolarization and cytoplasmic Ca2+ overload, which may partially explain the exacerbated neuronal damage caused by spermine. More importantly, blocking endogenous spermine synthesis significantly attenuates ischemic brain injury mediated by ASIC1a but not that by NMDA receptors. Thus, extracellular spermine contributes significantly to ischemic neuronal injury through enhancing ASIC1a activity. Our data suggest new neuroprotective strategies for stroke patients via inhibition of polyamine synthesis and subsequent spermine–ASIC interaction. PMID:21307247

  4. A review of the postulated mechanisms concerning the association of Helicobacter pylori with ischemic heart disease.

    PubMed

    Manolakis, Anastassios; Kapsoritakis, Andreas N; Potamianos, Spiros P

    2007-08-01

    Since its discovery, Helicobacter pylori has been implicated in the pathogenesis of several diseases, both digestive and extradigestive. Interestingly, the majority of the extradigestive-related literature is focused on two vascular manifestations: stroke and ischemic heart disease. Potential mechanisms for the establishment of a H. pylori-induced ischemic heart disease have been proposed with regard to chronic inflammation, molecular mimicry, oxidative modifications, endothelial dysfunction, direct effect of the microorganism on atherosclerotic plaques as well as changes regarding traditional or novel risk factors for ischemic heart disease or even platelet-H. pylori interactions. A positive link between H. pylori infection and ischemic heart disease has been suggested by a series of studies focusing on epidemiologic evidence, dyslipidemic alterations, upregulation of inflammatory markers or homocysteine levels, induction of hypercoagulability, oxidation of low-density lipoprotein, causation of impaired endothelial function, detection of H. pylori DNA in atherosclerotic plaques, and participation of certain antigens and antibodies in a cross-reactivity model. There are studies, however, which investigated the relationship between H. pylori and ischemic heart disease with regard to the same parameters and failed to confirm the suggested positive association. Further studies in the direction of interaction between H. pylori and the host's genotype as well as a quest for evidence towards novel risk factors for ischemic heart disease such as oxidative stress, vascular remodeling, vascular calcification, or vasomotor activity, may reveal a field of great interest, thus contributing to the determination of new potential mechanisms. PMID:17669100

  5. Does computed tomography permeability predict hemorrhagic transformation after ischemic stroke?

    PubMed Central

    Yen, Peggy; Cobb, Allison; Shankar, Jai Jai Shiva

    2016-01-01

    AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke. METHODS: We retrospectively analyzed our prospectively kept acute stroke database over five consecutive months for patients with symptoms of acute ischemic stroke (AIS) who had computed tomography (CT) perfusion (CTP) done at arrival. Patients included in the analyses also had to have a follow-up CT. The permeability-surface area product maps (PS) was calculated for the side of the ischemia and/or infarction and for the contralateral unaffected side at the same level. The cerebral blood flow map was used to delineate the ischemic territory. Next, a region of interest was drawn at the centre of this territory on the PS parametric map. Finally, a mirror region of interest was created on the contralateral side at the same level. The relative permeability-surface area product maps (rPS) provided an internal control and was calculated as the ratio of the PS on the side of the AIS to the PS on the contralateral side. A student t-test was performed after log conversion of rPS between patients with and without hemorrhagic transformation. Log conversion was used to convert the data into normal distribution to use t-test. For the group of patients who experienced intracranial bleed, a student t-test was performed between those with only petechial hemorrhage and those with more severe parenchymal hematoma with subarachnoid haemorrhage. RESULTS: Of 84 patients with AIS and CTP at admission, only 42 patients had a follow-up CT. The rPS derived using the normal side as the internal control was significantly higher (P = 0.003) for the 15 cases of hemorrhagic transformation (1.71 + 1.64) compared to 27 cases that did not have any (1.07 + 1.30). Patients with values above the overall mean rPS of 1.3 had an increased likelihood of subsequent hemorrhagic transformation. The sensitivity of using this score to predict

  6. Endothelial Dysfunction and Procoagulant Activity in Acute Ischemic Stroke

    PubMed Central

    Blum, Arnon; Vaispapir, Vladimir; Keinan-Boker, Lital; Soboh, Soboh; Yehuda, Hila; Tamir, Snait

    2012-01-01

    Endothelium-dependent vasodilator function may be regarded as an index of inflammation. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity, and outcome. Our aim was to measure systemic vascular function directly (using forearm flow mediated dilatation) in patients with acute ischemic stroke and to clarify whether recent acute ischemic stroke is associated with impaired vascular function. Patients who were not eligible for thrombolytic therapy because of delayed arrival were randomly recruited to the study after signing a consent form. All 43 patients were conscious and had an acute ischemic stroke. Brain CT was performed on admission, and clinical evaluation was carried out by a neurologist on admission and four days later. Vascular responsiveness was evaluated by ABI and by endothelial function measurements on admission. Levels of P-selectin were measured during the first 24 hrs and on day 4. Forty-three patients (28 men and 15 women) and 23 healthy men (control) were enrolled in the study. Patients were older (62.4±12.5 y vs 44.2±11.6 y, p=0.001), had worse endothelial dysfunction (–4.4±7.4% vs 16.6±7.6%, p=0.001), and had a higher BMI (28±6 vs 24±5, p=0.001). No gender effect was found in endothelial function (–5.1±7.8% vs –2.5±6.6%, p=0.25) and ABI (1.0±0.26 vs 1.0±0.5, p=0.29). However, men had lower BMIs compared to women (26.8±5.8 vs 31.4±5.5, p=0.01). The neurological scale decreased from 4.9±3.4 to 3.2±3.0 on day 4 (p=0.001). In men, it was 4.8±3.8 on admission, and decreased to 3.2±3.4 on day 4 (p=0.001). In women, it was 5.0±2.7, and decreased to 3.3±2.3 on day 4 (p=0.001). P-selectin levels were high on admission (68.0±55.5 pg/ml) and increased 4 days later (102.3±72.0 pg/ml) (p=0.01). Men had higher levels on admission (79.1± 66.7 pg/ml vs 48.9± 15.4 pg/ml, p=0.02) and rose on day 4 to 113.6±82.6 pg/ml (p=0.05); in women P

  7. Cerebral ischemic events in patients with pancreatic cancer

    PubMed Central

    Bonnerot, Mathieu; Humbertjean, Lisa; Mione, Gioia; Lacour, Jean-Christophe; Derelle, Anne-Laure; Sanchez, Jean-Charles; Riou-Comte, Nolwenn; Richard, Sébastien

    2016-01-01

    Abstract Stroke is a dramatic complication of pancreatic cancer with mechanisms related to oncological disease. A better description of the characteristics of cerebrovascular events would help better understand the pathogeny and protect vulnerable patients. We thus conducted a descriptive analysis of clinical, biological, and radiological features of patients from our centers and literature. We reviewed consecutive cases of patients who presented cerebrovascular events and pancreatic cancer in 4 stroke units in Lorrain (France) between January 1, 2009 and March 31, 2015, and all reported cases of literature. We identified 17 cases in our centers and 18 reported cases. Fifty-seven per cent of patients were male. Median age was 63 ± 14 years and ranged from 23 to 81 years. All cerebral events were ischemic. At the onset of stroke, pancreatic cancer had already been diagnosed in 59% of the patients in our centers for a mean time of 5.4 months. Five of them (29%) were being treated with gemcitabine and 2 (12%) with folfirinox. Adenocarcinoma at metastatic stage was reported in 82% of cases overall. Brain imaging revealed disseminated infarctions in 64%. High median levels of D-dimer (7600 ± 5 × 107 μg/L), C-reactive protein (63 ± 43 mg/L), and elevated prothrombin time (19 ± 6 seconds) were found. Thirty-six per cent of patients explored with echocardiography were diagnosed with nonbacterial thrombotic endocarditis. Ten of our patients received anticoagulant therapy as secondary stroke prevention without any documented recurrence. Nevertheless, outcome was poor with a median survival time of 28 ± 14 days after stroke onset. Cerebral ischemic events occur at advanced stages of pancreatic cancer, most likely by a thromboembolic mechanism. Disseminated infarctions and high D-dimer, C-reactive protein levels, and a high prothrombin time are the most constant characteristics found in this context. All patients should be screened for

  8. Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients.

    PubMed

    Zhang, Xia; Huang, Zhi-Chao; Lu, Tao-Sheng; You, Shou-Jiang; Cao, Yong-Jun; Liu, Chun-Feng

    2016-01-01

    The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (μmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 μmol/L) or lower UA levels (≤250 μmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 μmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 μmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 μmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 μmol/L were seven times more

  9. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients

    PubMed Central

    Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets’ tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight

  10. Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke

    PubMed Central

    Azab, Seham F.; Akeel, Nagwa E.; Abdalhady, Mohamed A.; Elhewala, Ahmed A.; Ali, Al Shymaa A.; Amin, Ezzat K.; Sarhan, Dina T.; Almalky, Mohamed A.A.; Elhindawy, Eman M.; Salam, Mohamed M.A.; Soliman, Attia A.; Abdellatif, Sawsan H.; Ismail, Sanaa M.; Elsamad, Nahla A.; Hashem, Mustafa I.A.; Aziz, Khalid A.; Elazouni, Osama M.A.; Arafat, Manal S.

    2016-01-01

    Abstract Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched. In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients. This was a case–control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects’ serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases. We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15–73]ng/mL) compared to the control group (median, 24[10–41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0

  11. Hypophosphatemic effect of niacin extended release in ischemic kidney disease

    PubMed Central

    Yasmeen, Ghazala; Dawani, Manohar Lal; Mahboob, Tabassum

    2015-01-01

    Ischemic nephropathy is an emerging cause of end stage renal disease, associated with many co-morbidities especially cardiovascular disease risk and derangement in calcium-phosphorus homeostasis resulting in hyperphosphatemia, influencing bones, a characteristic of advancing chronic kidney disease. The management of elevated serum phosphorus has been a challenge in this patient population with compromised kidney performance, as available phosphorus lowering agents possess many undesirable hazardous secondary effects and/or are very expensive. While niacin in different formulation is known to not only correct dyslipidemia but also reduce phosphorus level, but its clinical use restricted owing to side effects. The objective of present study is to evaluate such effect of niacin extended release (NER) in ischemic nephropathy. The chronic kidney disease patients fulfilling the pre-defined criteria were randomly categorized into two groups of equal size (n=60) and prescribed either atorvastatin 20 mg/day or NER 500 mg/day with the same dose of statin for four months. A control of 50 healthy characters matched was also incorporated for local reference range. Baseline and follow up phosphorus concentration was measured and means were compared using t-test at SPSS version 17 with 0.05 chosen alpha. There was no difference in the baseline levels in both groups while significant (p<0.001) hyperphosphatemia was observed in both units as compared with healthy controls. The administration of atorvastatin alone for four weeks showed an insignificant decrease in phosphorus, whereas, NER significantly reduced phosphorus (p<0.001). The mean percent change from baseline to follow up further endorsed the finding as statin alone brought -13.8 % reduction in phosphorus and NER -47 % from baseline. NER, at its lowest prescribed dose once a day was well tolerated by most of the patients and demonstrated significant goal achievement of phosphorus reduction. It is concluded that NER even at

  12. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

    PubMed

    Cevik, Ozge; Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into

  13. Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage

    PubMed Central

    Zhao, Xiurong; Wang, Huan; Sun, Guanghua; Zhang, Jie; Edwards, Nancy J.

    2015-01-01

    After ischemic stroke, various damage-associated molecules are released from the ischemic core and diffuse to the ischemic penumbra, activating microglia and promoting proinflammatory responses that may cause damage to the local tissue. Here we demonstrate using in vivo and in vitro models that, during sublethal ischemia, local neurons rapidly produce interleukin-4 (IL-4), a cytokine with potent anti-inflammatory properties. One such anti-inflammatory property includes its ability to polarize macrophages away from a proinflammatory M1 phenotype to a “healing” M2 phenotype. Using an IL-4 reporter mouse, we demonstrated that IL-4 expression was induced preferentially in neurons in the ischemic penumbra but not in the ischemic core or in brain regions that were spared from ischemia. When added to cultured microglia, IL-4 was able to induce expression of genes typifying the M2 phenotype and peroxisome proliferator activated receptor γ (PPARγ) activation. IL-4 also enhanced expression of the IL-4 receptor on microglia, facilitating a “feedforward” increase in (1) their expression of trophic factors and (2) PPARγ-dependent phagocytosis of apoptotic neurons. Parenteral administration of IL-4 resulted in augmented brain expression of M2- and PPARγ-related genes. Furthermore, IL-4 and PPARγ agonist administration improved functional recovery in a clinically relevant mouse stroke model, even if administered 24 h after the onset of ischemia. We propose that IL-4 is secreted by ischemic neurons as an endogenous defense mechanism, playing a vital role in the regulation of brain cleanup and repair after stroke. Modulation of IL-4 and its associated pathways could represent a potential target for ischemic stroke treatment. SIGNIFICANCE STATEMENT Depending on the activation signal, microglia/macrophages (MΦ) can behave as “healing” (M2) or “harmful” (M1). In response to ischemia, damaged/necrotic brain cells discharge factors that polarize MΦ to a M1-like

  14. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    SciTech Connect

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalen; Palmqvist, Lars; Jeppsson, Anders; Hulten, Lillemor Mattsson

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  15. [Pathology and strategies for the treatment of ischemic brain injury].

    PubMed

    Takagi, Norio

    2009-10-01

    Cerebral ischemia, a pathological condition in which brain tissue experiences a shortage or lack of glucose and oxygen, provokes an irreversible neurodegenerative disorder that may lead clinically to a progressive dementia and global cognitive deterioration. Accumulating evidence indicates many biochemical cascades that lead ultimately to ischemia-induced cell death. However, the cellular and molecular aspects of cerebral ischemia are not yet fully understood. Since the pattern of pathophysiological alterations is not the same for all cells in the ischemic brain, a good understanding of the cellular and molecular alterations induced by cerebral ischemia is needed to develop strategies for the treatment of stroke. This review summarizes recent advances concerning the pathophysiological alterations caused by cerebral ischemia, focusing on the modification of properties of glutamate receptors, which modification may be linked to the development of cerebral infarction. Furthermore, the effects of hepatocyte growth factor on learning dysfunction and cerebral vessel injury after cerebral ischemia are also summarized. Finally, this review describes a possible ameliorative effect of the injection of exogenous neural progenitor cells on cerebral ischemia-induced learning and memory dysfunction. PMID:19797876

  16. Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

    PubMed Central

    XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

    2016-01-01

    The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

  17. Cold ischemic organ preservation: lessons from natural systems.

    PubMed

    Storey, Kenneth B

    2004-07-01

    Mammalian hibernators offer natural models for investigating solutions to the metabolic injuries that accrue during cold ischemic storage of human organs removed for transplant. Knowledge of the biochemical mechanisms that regulate and stabilize metabolism to ensure long-term viability in the hypometabolic, hypothermic state of hibernation could lead to applied treatments that could increase the time that excised organs can be maintained in cold storage and/or improve recovery of function after implantation. New research has documented the widespread role of reversible protein phosphorylation control of metabolism in achieving the coordinated suppression of metabolic rate that greatly extends viability during torpor. Analysis of hibernation-induced gene expression is proving to be of crucial importance for identifying the genes and proteins that are up-regulated to address organ-specific concerns during torpor. In particular, the power of complementary deoxyribonucleic acid (cDNA) array screening is identifying families of proteins that are up-regulated during hibernation (eg, serpins, heat shock proteins, antioxidants, membrane transporters) and highlighting previously unrecognized areas of cellular metabolism as contributing to the hibernation phenotype. These offer new targets for innovative applied treatments that could enhance cytoprotection and cold ischemia survival of organ explants. PMID:15551654

  18. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Gonzales-Portillo, Gabriel S.; Reyes, Stephanny; Aguirre, Daniela; Pabon, Mibel M.; Borlongan, Cesar V.

    2014-01-01

    Treatments for neonatal hypoxic-ischemic encephalopathy (HIE) have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke and providing insights on the potential of cell therapy currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in stem cell therapeutics as an emerging paradigm for stroke or STEPS, which have been recently modified to Baby STEPS to cater for the “neonatal” symptoms of HIE. These guidelines recognized that neonatal HIE exhibit distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE. PMID:25161645

  19. Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

    PubMed Central

    Liu, Li; Goldberg, Ira J.

    2015-01-01

    Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

  20. The Effects of Air Pollution on Ischemic Stroke Admission Rate

    PubMed Central

    Alimohammadi, Hossein; Fakhri, Sara; Derakhshanfar, Hojjat; Hosseini-Zijoud, Seyed-Mostafa; Safari, Saeed

    2016-01-01

    The present study aimed to determine the relationship between the level of air pollutants and the rate of ischemic stroke (IS) admissions to hospitals. In this retrospective cross-sectional study, stroke admissions (January-March 2012 and 2013) to an emergency department and air pollution and meteorological data were gathered. The relationship between air pollutant levels and hospital admission rates were evaluated using the generalize additive model. In all 379 patients with IS were referred to the hospital (52.5% male; mean age 68.2±13.3 years). Both transient (p<0.001) and long-term (p<0.001) rises in CO level increases the risk of IS. Increased weekly (p<0.001) and monthly (p<0.001) average O3 levels amplifies this risk, while a transient increase in NO2 (p<0.001) and SO2 (p<0.001) levels has the same effect. Long-term changes in PM10 (p<0.001) and PM2.5 (p<0.001) also increase the risk of IS. The findings showed that the level of air pollutants directly correlates with the number of stroke admissions to the emergency department. PMID:26866000

  1. Sleep deprivation attenuates inflammatory responses and ischemic cell death.

    PubMed

    Weil, Zachary M; Norman, Greg J; Karelina, Kate; Morris, John S; Barker, Jacqueline M; Su, Alan J; Walton, James C; Bohinc, Steven; Nelson, Randy J; DeVries, A Courtney

    2009-07-01

    Although the biological function of sleep remains uncertain, the consequences of sleep deprivation are well-described and are reported to be detrimental to cognitive function and affective well-being. Sleep deprivation also is strongly associated with elevated risk factors for cardiovascular disease. We used a mouse model of cardiac arrest/cardiopulmonary resuscitation to test the hypothesis that acute sleep deprivation would exacerbate neuroinflammation and neurodegeneration after global ischemia. The resulting data led to a rejection of our hypothesis that sleep deprivation is necessarily detrimental. Indeed, acute sleep deprivation (ASD) was associated with a reduction in ischemia-induced interleukin 1beta (IL-1beta) gene expression and attenuation of neuronal damage in the hippocampus. Further, sleep deprivation increased gene expression of two anti-inflammatory cytokines, IL-6 and IL-10 that are associated with improved ischemic outcome. To determine whether the anti-inflammatory properties of ASD were specific to ischemia, mice were treated systemically with lipopolysaccharide (LPS), a potent inflammogen. Acute sleep deprivation attenuated the central and peripheral increase in tumor necrosis factor-alpha (TNFalpha) and increased IL-10 expression. Together, the ischemia and LPS data suggest that, ASD produces an anti-inflammatory bias that could be exploited to improve medical procedures that are compromised by inflammation. PMID:19409382

  2. Vitamin D deficiency aggravates ischemic acute kidney injury in rats

    PubMed Central

    de Bragança, Ana Carolina; Volpini, Rildo A; Canale, Daniele; Gonçalves, Janaína G; Shimizu, Maria Heloisa M; Sanches, Talita R; Seguro, Antonio C; Andrade, Lúcia

    2015-01-01

    Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI. PMID:25780095

  3. Cardioprotection against experimental myocardial ischemic injury using cornin.

    PubMed

    Xu, Y; Xu, Y; Luan, H; Jiang, Y; Tian, X; Zhang, S

    2016-02-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt. PMID:26871971

  4. Acute ischemic colitis secondary to air embolism after diving

    PubMed Central

    Payor, Austin Daniel; Tucci, Veronica

    2011-01-01

    Ischemic colitis (IC) secondary to air embolism from decompression sickness or barotrauma during diving is an extremely rare condition. After extensive review of the available literature, we found that there has been only one reported case of IC secondary to air embolism from diving. Although air embolization from diving and the various medical complications that follow have been well documented, the clinical manifestation of IC from an air embolism during diving is very rare and thus far unstudied. Common symptoms of IC include abdominal pain, bloody or non-bloody diarrhea or nausea or vomiting or any combination. Emergency physicians and Critical Care specialists should consider IC as a potential diagnosis for a patient with the above-mentioned symptoms and a history of recent diving. We report a case of IC from air embolism after a routine dive to 75 feet below sea level in a 53-year-old White female who presented to a community Emergency Department complaining of a 2-day history of diffuse abdominal pain and nausea. She was diagnosed by colonoscopy with biopsies and treated conservatively with antibiotics, bowel rest, and a slow advancement in diet. PMID:22096777

  5. Effect of melatonin on kidney cold ischemic preservation injury

    PubMed Central

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2nd, 24th, 36th, and 48th hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48th hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID:24179573

  6. Experimental models of perinatal hypoxic-ischemic brain damage.

    PubMed

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia. PMID:8311995

  7. Applications of laser in ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Chen, Mingzhe; Zhang, Yongzhen

    1999-09-01

    Current data demonstrate that laser coronary angioplasty is most useful in complex lesions not well suited for percutaneous transluminal coronary angioplasty (PTCA). It is not `stand-alone' procedure, and should be considered an adjunct to PTCA or stenting. To date, there are not data supporting reduction of restenosis. Direct myocardial revascularization (DMR), either transmyocardial revascularization (TMR) or percutaneous (catheter-based) myocardial revascularization (PMR), uses laser to create channels between ischemic myocardium and left ventricular cavity. Candidates include patients with chronic, severe, refractory angina and those unable to undergo angioplasty or bypass surgery because conduits or acceptable target vessels are lacking. Although the mechanisms of action of DMR have not yet been clearly elucidated, but several theories have been proposed, including channel patency, angiogenesis, and denervation. TMR, typically requiring open thoracotomy, is effective for improving myocardial perfusion and reducing angina. Pilot studies demonstrate that clinical application of PMR is feasible and safe and effective for decreasing angina. Late sequelae also remain to be determined. An ongoing randomized clinical trial is comparing PMR with conventional medical therapy in patients with severe, refractory angina and disease unamenable to angioplasty or bypass surgery.

  8. Critical Care for Patients with Massive Ischemic Stroke

    PubMed Central

    Koh, Younsuck; Choi, H. Alex; Lee, Kiwon

    2014-01-01

    Malignant cerebral edema following ischemic stroke is life threatening, as it can cause inadequate blood flow and perfusion leading to irreversible tissue hypoxia and metabolic crisis. Increased intracranial pressure and brain shift can cause herniation syndrome and finally brain death. Multiple randomized clinical trials have shown that preemptive decompressive hemicraniectomy effectively reduces mortality and morbidity in patients with malignant middle cerebral artery infarction. Another life-saving decompressive surgery is suboccipital craniectomy for patients with brainstem compression by edematous cerebellar infarction. In addition to decompressive surgery, cerebrospinal fluid drainage by ventriculostomy should be considered for patients with acute hydrocephalus following stroke. Medical treatment begins with sedation, analgesia, and general measures including ventilatory support, head elevation, maintaining a neutral neck position, and avoiding conditions associated with intracranial hypertension. Optimization of cerebral perfusion pressure and reduction of intracranial pressure should always be pursued simultaneously. Osmotherapy with mannitol is the standard treatment for intracranial hypertension, but hypertonic saline is also an effective alternative. Therapeutic hypothermia may also be considered for treatment of brain edema and intracranial hypertension, but its neuroprotective effects have not been demonstrated in stroke. Barbiturate coma therapy has been used to reduce metabolic demand, but has become less popular because of its systemic adverse effects. Furthermore, general medical care is critical because of the complex interactions between the brain and other organ systems. Some challenging aspects of critical care, including ventilator support, sedation and analgesia, and performing neurological examinations in the setting of a minimal stimulation protocol, are addressed in this review. PMID:25328873

  9. New therapeutic effects of cilostazol in patients with ischemic disorders.

    PubMed

    Biscetti, Federico; Ferraccioli, Gianfranco; Flex, Andrea

    2015-01-01

    Cilostazol (CIL) is effective for the treatment of patients with peripheral arterial disease (PAD). CIL is an orally administered drug with multiple effects, including anti-platelets aggregation, favorable functions on plasmatic lipids and vasodilator ones, but how these effects might be related to improvement in patients walking affected by PAD is not fully understood. The latest data demonstrate that nitric oxide (NO) is induced by CIL through endothelial nitric oxide synthase (eNOS) activation via a cyclic-AMP (cAMP)/ protein kinase A (PKA)- and PI3K/Akt- dependent mechanism. This mechanism is also responsible for the vasodilatation dependent on endothelium which characterized patients receiving CIL. Other investigators have found that CIL notably reduces the exercise-induced host-inflammatory response in PAD patients, and consequently it improves lipid hydroperoxides and cell-adhesion molecule levels. We recently reported that CIL is able to cause neoangiogenesis in vivo by stimulating the production of proangiogenic proteins, such as vascular endothelial growth factor (VEGF), that increase levels of Endothelial progenitor cells (EPCs) and the formation of new blood vessels. The mechanisms of action of this drug are several and are not clear and established. The objective of the present review is to analyze the existing data about the therapeutic effects of CIL, with the purpose of providing practical indications about this topic for the management of subjects affected by ischemic disorders. PMID:26156267

  10. The Effects of Air Pollution on Ischemic Stroke Admission Rate.

    PubMed

    Alimohammadi, Hossein; Fakhri, Sara; Derakhshanfar, Hojjat; Hosseini-Zijoud, Seyed-Mostafa; Safari, Saeed; Hatamabadi, Hamid Reza

    2016-01-01

    The present study aimed to determine the relationship between the level of air pollutants and the rate of ischemic stroke (IS) admissions to hospitals. In this retrospective cross-sectional study, stroke admissions (January-March 2012 and 2013) to an emergency department and air pollution and meteorological data were gathered. The relationship between air pollutant levels and hospital admission rates were evaluated using the generalize additive model. In all 379 patients with IS were referred to the hospital (52.5% male; mean age 68.2±13.3 years). Both transient (p<0.001) and long-term (p<0.001) rises in CO level increases the risk of IS. Increased weekly (p<0.001) and monthly (p<0.001) average O3 levels amplifies this risk, while a transient increase in NO2 (p<0.001) and SO2 (p<0.001) levels has the same effect. Long-term changes in PM10 (p<0.001) and PM2.5 (p<0.001) also increase the risk of IS. The findings showed that the level of air pollutants directly correlates with the number of stroke admissions to the emergency department. PMID:26866000

  11. Cardioprotection against experimental myocardial ischemic injury using cornin

    PubMed Central

    Xu, Y.; Xu, Y.; Luan, H.; Jiang, Y.; Tian, X.; Zhang, S.

    2016-01-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt. PMID:26871971

  12. Neurological outcome after arterial ischemic stroke in children

    PubMed Central

    Nasiri, Jafar; Ariyana, Alireza; Yaghini, Omid; Ghazavi, Mohammad Reza; Keikhah, Mojtaba; Salari, Mehri

    2016-01-01

    Background: Stroke is an important cause of disability in children. Pediatric stroke may be due to significant permanent cognitive and motor handicap in children. In this study, we evaluated long-term outcomes of stroke in pediatric patients who have been discharged with definite diagnosis of stroke in Tehran Mofid children’s Hospital and Imam Hossein children’s Hospital located in Isfahan, Iran, from 2005 to 2012. Materials and Methods: A total of 53 children with stroke were included in the study. Stroke outcomes as motor disability, seizures, and cognitive dysfunctions were assessed. Results: After a median follow-up of 4 years, 15 (29%) patients experienced full recovery. Thirty-eight (71%) patients had some degree of neurological handicap. Conclusion: Approximately 70% of children with arterial ischemic stroke suffer from long-term neurological disabilities including motor deficits, cognitive impairment, and late seizures. Stroke recurrence is the most important risk factor responsible for severe adverse neurological outcomes in pediatric stroke. PMID:27376046

  13. Ischemic stroke and incidental finding of a right atrial lipoma.

    PubMed

    Censi, Stefano; Squeri, Angelo; Baldelli, Marco; Parizi, Sepideh Torabi

    2013-12-01

    A young man presented with recurrent ischemic stroke under antiplatelet therapy. A patent foramen ovale (PFO) was diagnosed by transesophageal echocardiography (TEE) and the patient was referred to our institution for percutaneous closure. An echogenic mass in the right atrium was detected during the intraprocedural TEE. The interventional team decided to perform transcatheter closure of PFO under fluoroscopy and TEE guide, without complications. Subsequent cardiac magnetic resonance (CMR) imaging confirmed an encapsulated and hyperintense mass located in the roof of the right atrium. The signal intensity pattern and the absence of gadolinium contrast uptake allowed a confident diagnosis of lipoma. Cardiac lipoma accounts for about 10% of primary cardiac tumors and frequently rises from the epicardial fat tissue. Echocardiographic images can remain equivocal about the nature of the mass and CMR offers a substantial contribution to a correct diagnosis. The tumor usually appears encapsulated and asymptomatic, but dyspnea, atrial and ventricular arrhythmias and, rarely, peripheral embolization have been reported. To our knowledge, this is the second case reported on paradoxical embolization associated with right atrial lipoma. Although the relationship of cardiac lipoma with stroke is not well defined, the potential proembolic significance of this lesion cannot be excluded, especially when a PFO coexists. PMID:24149062

  14. Polycyclic aromatic hydrocarbons and fatal ischemic heart disease

    SciTech Connect

    Burstyn, I.; Kromhout, H.; Partanen, T.; Svane, O.; Langard, S.; Ahrens, W.; Kauppinen, T.; Stucker, I.; Shaham, J.; Heederik, D.; Ferro, G.; Heikkila, P.; Hooiveld, M.; Johansen, C.; Randem, B.G.; Boffetta, P.

    2005-11-01

    Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure-response relation has not been demonstrated. We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m{sup 3} or higher, for which the relative risk was 1.64(95% confidence interval = 1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association.

  15. Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.

    2016-01-01

    Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829

  16. Brain lipidomes of subcortical ischemic vascular dementia and mixed dementia.

    PubMed

    Lam, Sin Man; Wang, Yuting; Duan, Xinrui; Wenk, Markus R; Kalaria, Raj N; Chen, Christopher P; Lai, Mitchell K P; Shui, Guanghou

    2014-10-01

    Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD. PMID:24684787

  17. Shared genetic basis for migraine and ischemic stroke

    PubMed Central

    Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno

    2015-01-01

    Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857

  18. Diffusion of radiotracers in normal and ischemic brain slices.

    PubMed

    Patlak, C S; Hospod, F E; Trowbridge, S D; Newman, G C

    1998-07-01

    Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra. PMID:9663508

  19. Anterior ischemic optic neuropathy in association with optic nervehead drusen

    PubMed Central

    Megur, Bharathi; Megur, Deepak; Megur, Umesh; Reddy, Sandeep

    2014-01-01

    Optic nerve head drusen (ONHD) are incidental ophthalmologic finding in the optic nerve. Patients with ONHD are often asymptomatic, but sometimes present with transient visual obscuration's (TVO), the reported incidence of which is 8.6%. Optic nerve head drusen are of two types: Superficial; visible and deep. The deep-buried drusen mimic papilledema. Because of the varied presentation deep-buried drusen pose a diagnostic challenge to the ophthalmologists. In young patients, they are mistaken for papilledema as it is clinically difficult to detect a buried drusen in the optic nerve head, but are seen on the surface with aging as the retinal nerve fiber layer thins out. They are observed as pale yellow lesions more often located towards the poles. Clinical examination aided with diagnostic tests like computed tomography (CT) orbits and ultrasound B scan can help establish the diagnosis. Herein, we report a rare case of optic nerve head drusen in a young lady, who presented with loss of vision and clinical evaluation and investigations suggested ONHD with anterior ischemic optic neuropathy. PMID:25116784

  20. Increased risk of ischemic heart disease among subjects with cataracts

    PubMed Central

    Hu, Wei-Syun; Lin, Cheng-Li; Chang, Shih-Sheng; Chen, Ming-Fong; Chang, Kuan-Cheng

    2016-01-01

    Abstract Background: Association between cataract and the risk of ischemic heart disease (IHD) development is not completely clear. Purpose: The primary aim of the study was to evaluate the association between cataract and the risk of incident IHD. The secondary aim was to investigate the subsequent IHD risk of patients with cataracts undergoing cataract surgery. Methods: Retrospective data from the Longitudinal Health Insurance Database 2000 (LHID2000) was analyzed. Study participants were composed of patients with cataracts (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 366) (n = 32,456), and a comparison cohort without the cataracts (n = 32,456) from 2000 to 2010. Cox proportional hazards regression was used to address the hazard ratio (HR) of IHD associated with cataract. Results: Within 12 years of follow up, the overall incidence rates of IHD were 24.2 per 1000 person-years in the cataract cohort and 18.2 per 1000 person-years in the noncataract cohort with an adjusted hazard ratio (aHR) of 1.35 (95% CI = 1.29–1.41; P < 0.001). Furthermore, the cataract patients undergoing cataract surgery were associated with a higher risk of IHD compared with those cataract patients without surgery (aHR = 1.07, 95% CI: 1.01–1.14; P < 0.05). Conclusions: Our finding suggested that patients with cataracts are at an increased risk of subsequent IHD development. PMID:27428198

  1. Estrogenic Impact on Cardiac Ischemic/Reperfusion Injury.

    PubMed

    Sivasinprasasn, Sivaporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-02-01

    The increase in cardiovascular disease and metabolic syndrome incidence following the onset of menopause has highlighted the role of estrogen as a cardiometabolic protective agent. Specifically regarding the heart, estrogen induced an improvement in cardiac function, preserved calcium homeostasis, and inhibited the mitochondrial apoptotic pathway. The beneficial effects of estrogen in relation to cardiac ischemia/reperfusion (I/R) injury, such as reduced infarction and ameliorated post-ischemic recovery, have also been shown. Nevertheless, controversial findings exist and estrogen therapy is reported to be related to a higher rate of thromboembolic events and atrial fibrillation in post-menopausal women. Therefore, greater clarification is needed to evaluate the exact potential of estrogen use in cases of cardiac I/R injury. This article reviews the effects of estrogen, in both acute and chronic treatment, and collates the studies with regard to their in vivo, in vitro, or clinical trial settings in cases of cardiac I/R injury and myocardial infarction. PMID:26786980

  2. Effects of kinesiotherapy in ischemic lesion and reperfusion in rats

    PubMed Central

    Moscardini, Flavia; Barbosa, Everton Horiquini; Garcia, Estela Fagionato; Borges, Ana Paula Oliveira; Bachur, José Alexandre; Quemelo, Paulo Roberto Veiga

    2012-01-01

    Objective To investigate the effect of kinesiotherapy on the functionality of the pelvic limb of rats after ischemic and reperfusion injury. Methods 10 rats were divided into two groups, GI (control) and GII (kinesiotherapy). All the animals underwent ischemia for a period of three hours, followed by tissue reperfusion. In Group GII, non-resistive systemic kinesiotherapy was performed (swimming) in three weekly sessions of 50 minutes, over a period of four weeks, while the GI animals remained at rest. Functional analysis of motor behavior was evaluated weekly. The animals were then sacrificed, and the soleus and gastrocnemius muscles and the sciatic nerve removed for histopathological analysis. Results There was a significant recovery of motor behavior with kinesiotherapeutic treatment during the four weeks of treatment. However, the histological examination of the tissues showed no morphological changes of cell injury and repair. Conclusion It was not possible to affirm that the exercise was effective in cell repair, because neither of the groups (control and experimental) showed any histological difference. On the other hand, systemic kinesiotherapy showed a beneficial effect on functional rehabilitation after ischemia and reperfusion. Level of evidence III, Case-Control Study. PMID:24453592

  3. Ischemic stroke management in West Scotland: a chart review

    PubMed Central

    Verpillat, Patrice; Dorey, Julie; Guilhaume-Goulant, Chantal; Dabbous, Firas; Aballéa, Samuel

    2015-01-01

    Background Little information is available about the long-term management of ischemic stroke (IS) in West Scotland. In this study we aim to describe the management of IS at onset, admission, and during follow-up among patients who survived an IS event. Methods General practitioners (GPs) (n=20) were randomly selected to recruit IS patients and extract data about patient characteristics, hospitalizations, discharge, and ambulatory care from GP databases, hospital letters, and direct contact with patients and their relatives. Descriptive analyses were conducted. Results One hundred and one patients were included, with a mean age of 65.6±13.4. About half of the patients contacted their GPs at the time of onset (45.4%). Cardiovascular history was prevalent in 29.7% of cases, and 14% of all cases were recurrences. Of the patients, 89 (88%) were hospitalized with mean length of stay (LOS) 11.8 days. Treatment was administered on average within 12.9 hours of admission and 23.6% of the admitted patients received thrombolytic treatment. During the 1-year follow-up period, 33.6% of patients were rehospitalized and the mean LOS was 15.1±29.5 days. Further, patients on average sought nursing care (10.9%), physical therapy (45.5%), occupational therapy (27.7%), speech therapy (12.9%), and professional caregivers (12%). Conclusion The health-care resource utilization of IS patients is a major driver of economic burden. PMID:27123179

  4. Ischemic spinal cord infarction in children without vertebral fracture

    PubMed Central

    Nance, Jessica R.; Golomb, Meredith R.

    2007-01-01

    Spinal cord infarction in children is a rare condition which is becoming more widely recognized. There are few reports in the pediatric literature characterizing etiology, diagnosis, treament and prognosis. The risk factors for pediatric ischemic spinal cord infarction include obstruction of blood flow associated with cardiovascular compromise or malformation, iatrogenic or traumatic vascular inujury, cerebellar herniation, thrombotic or embolic disease, infection, and vasculitis. In many children the cause of spinal cord ischemia in the absence of vertebral fracture is unknown. Imaging diagnosis of spinal cord ischemia is often difficult due to the small transverse area of the cord, cerebrospinal fluid artifact and inadequate resolution of MRI. Physical therapy is the most important treatment option. The prognosis is dependent on the level of spinal cord damage, early identification and reversal of ischemia, and follow-up with intensive physical therapy and medical support. In addition to summarizing the literature regarding spinal cord infarction in children without vertebral fracture, this review article adds two cases to the literature which highlight the difficulties and controversies in the management of this condition. PMID:17437902

  5. Lasers in the treatment of ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Zhang, Yongzhen; Chen, Mingzhe

    2000-10-01

    Myocardial revascularization by laser is a new treatment modality for chronic, severe, refractory angina in the patients with coronary heart disease that is not amenable to angioplasty (PTCA) or bypass surgery (CABG). Transmyocardial revascularization (TMR), typically requiring open thoracotomy, uses laser to create channels that would directly carry blood from left ventricular cavity into the ischemic myocardium. Current data indicate that TMR may provide these patients with improvement in angina severity, quality of life, and myocardial perfusion. The greatest potential future use of TMR is as an adjunct to CABG in patients with disease that prevents bypass grafting due to lack of distal targets or a conduit. Recently, as percutaneous (catheter-based) myocardial revascularization (PMR) has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle. The early results with PMR seem encouraging. Randomized clinical trial has demonstrated symptomatic improvement and increased exercise capacity. The risk: benefit ratio for PMR appears to be much more favorable than that for TMR. The mechanisms of action of them have not yet been clearly elucidated, and several theories have been proposed, including channel patency, angiogenesis, denervation, and placebo effect. The challenge of TMR/PMR is related to improvement of perioperative outcomes and long-term survival without worsening of left ventricular function. In future, it may be feasible to combine TMR/PMR with intramyocardial delivery of angiogenic growth factors to induce further new blood vessel formation.

  6. [Caffeinol: a neuroprotective action in ischemic brain damage].

    PubMed

    Bednarski, Jerzy; Gasińska, Karolina; Straszewski, Tomasz; Godek, Magdalena; Tutka, Piotr

    2015-01-01

    Caffeinol--a combination of ethanol and caffeine in appropriate concentrations--exerts neuroprotective and anticonvulsive action. Research conducted on rats in models of ischemic brain damage have shown that caffeinol decreases the size of cortical damage by about 80%, improves motional coordination and memory. The sooner caffeinol was administered, the better were beneficial therapeutic effects. What is more, the medicine may be safely combined with other methods used in stroke treatment, such as hypothermia and thrombolysis, what additionally increases its neuroprotective influence. Research on people have shown that caffeinol is less effective as neuroprotective agent in patients abusing alcohol, while chronic intake of caffeine does not influence its activity. Mechanism of its activity is not known yet, however, it is assumed that it bases on an antagonism of NMDA receptors. Regarding the fact that the most of strokes in humans concern subcortical areas, it is justified to conduct further research on caffeinol, which would involve other brain structures, thus allowing to define its use in clinical practice. PMID:27012130

  7. Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress.

    PubMed

    Kolwicz, Stephen C; Liu, Li; Goldberg, Ira J; Tian, Rong

    2015-08-01

    Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain-mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

  8. A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat.

    PubMed

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-04-01

    Remote ischemic perconditioning (RIPerC) and ischemic postconditioning (IPOC) are well-acknowledged neuroprotective procedures during ischemic injury. The present study established a combined RIPerC and IPOC (RIPerC + IPOC) model in rats and studied how it would regulate the autophagy process and affect HMGB1 levels in a rat model of middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with RIPerC by fastening and release of the left hind limb to achieve 4 cycles of 5 min remote ischemia reperfusion, 40 min prior to cerebral reperfusion, and then treated with IPOC by exposing the cerebral middle artery to 3 cycles of 30 s reperfusion/30 s occlusion at the onset of cerebral reperfusion. Infarction volumes, neurological deficits, and pathological changes were assessed 24 h after ischemia. The autophagy activator rapamycin (RAP) and the autophagy inhibitor 3-methyladenine (3-MA) were administrated for further mechanism. The expression and location of HMGB1 and the autophagy-related proteins like LC3, Beclin1, and P62 as well as plasma HMGB1 levels were measured. Our results suggested that RIPerC + IPOC attenuated plasma HMGB1 levels to intensify its neuroprotective effect against cerebral ischemic reperfusion injury via inhibiting the autophagy process. PMID:26852332

  9. Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury

    PubMed Central

    Kim, S Y; Shim, M S; Kim, K-Y; Weinreb, R N; Wheeler, L A; Ju, W-K

    2014-01-01

    Cyclosporin A (CsA) inhibits the opening of the mitochondrial permeability transition pore (MPTP) by interacting with cyclophilin D (CypD) and ameliorates neuronal cell death in the central nervous system against ischemic injury. However, the molecular mechanisms underlying CypD/MPTP opening-mediated cell death in ischemic retinal injury induced by acute intraocular pressure (IOP) elevation remain unknown. We observed the first direct evidence that acute IOP elevation significantly upregulated CypD protein expression in ischemic retina at 12 h. However, CsA prevented the upregulation of CypD protein expression and promoted retinal ganglion cell (RGC) survival against ischemic injury. Moreover, CsA blocked apoptotic cell death by decreasing cleaved caspase-3 protein expression in ischemic retina. Of interest, although the expression level of Bcl-xL protein did not show a significant change in ischemic retina treated with vehicle or CsA at 12 h, ischemic damage induced the reduction of Bcl-xL immunoreactivity in RGCs. More importantly, CsA preserved Bcl-xL immunoreactivity in RGCs of ischemic retina. In parallel, acute IOP elevation significantly increased phosphorylated Bad (pBad) at Ser112 protein expression in ischemic retina at 12 h. However, CsA significantly preserved pBad protein expression in ischemic retina. Finally, acute IOP elevation significantly increased mitochondrial transcription factor A (Tfam) protein expression in ischemic retina at 12 h. However, CsA significantly preserved Tfam protein expression in ischemic retina. Studies on mitochondrial DNA (mtDNA) content in ischemic retina showed that there were no statistically significant differences in mtDNA content among control and ischemic groups treated with vehicle or CsA. Therefore, these results provide evidence that the activation of CypD-mediated MPTP opening is associated with the apoptotic pathway and the mitochondrial alteration in RGC death of ischemic retinal injury. On the basis

  10. Telomere Length and Ischemic Stroke in Women: A Nested Case-Control Study

    PubMed Central

    Schürks, Markus; Prescott, Jennifer; Dushkes, Rimma; De Vivo, Immaculata; Rexrode, Kathryn M.

    2013-01-01

    Background Telomere shortening has been implicated in cardiovascular disease. However, prospective data on the association between relative telomere length (RTL) and ischemic stroke are scarce and inconclusive. Methods We used a nested case-control design among women participating in the prospective Nurses’ Health Study. Participants provided blood samples in 1990 and were followed through 2006. Women with confirmed incident ischemic stroke were matched to controls by age, smoking, postmenopausal status, and postmenopausal hormone use. Quantitative PCR was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median. Results Data on RTL were available from 504 case-control pairs. Results did not suggest an association between RTL and ischemic stroke. The odds ratio for ischemic stroke was 0.82 (95% confidence interval [CI] 0.52–1.32) comparing lowest to the highest RTL quartile and 0.90 (95% CI 0.65–1.24) comparing RTL below the median to RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischemic stroke (54 case-control pairs; lowest vs. highest quartile OR=1.99, 95%CI 0.26–14.9); however, results were statistically insignificant. Conclusion In this large nested case-control study among women RTL was not associated with ischemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke additional research is warranted. PMID:23521613

  11. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke

    PubMed Central

    Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash

    2016-01-01

    Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350

  12. A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

    PubMed

    Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K

    2014-01-01

    We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. PMID:25224310

  13. Fruit and vegetable consumption, ethnicity and risk of fatal ischemic heart disease

    PubMed Central

    Sharma, Sangita; Vik, Shelly; Kolonel, Laurence N.

    2016-01-01

    Objective Mortality rates from ischemic heart disease vary among ethnic groups. Dietary intake of fruit and vegetables has been associated with a lower risk of ischemic heart disease, but ethnic-specific data are limited. Design Prospective cohort study. Setting Hawaii and Los Angeles County, between 1993 and 1996. Participants These analyses included 164,617 older adults age 45 to 75, representing five ethnic groups who were enrolled in the Multiethnic Cohort Study. Dietary data were collected at baseline using a validated food frequency questionnaire and fatal ischemic heart disease cases were identified up to December 31, 2001. Associations between fruit and vegetable consumption and fatal ischemic heart disease were examined using multivariate Cox proportional hazard models. Results The associations between fruit and vegetable intake and fatal ischemic heart disease were similar among the five ethnic groups. When data for the ethnic groups were combined, higher vegetable intake was associated with a protective effect against ischemic heart disease in men with all intake levels above 2.3 servings per day (over 6.6 servings per day: hazard ratio, 0.73; 95% confidence interval, 0.58–0.92), and for women with intakes levels between 3.4 and 6.6 servings per day (4.6 to 6.6 servings per day: hazard ratio, 0.77; 95% confidence interval, 0.59–0.99). There was no evidence of an association for fruit intake. Conclusions Associations between fruit and vegetable intake and ischemic heart disease do not appear to vary among ethnic groups. Additional research is needed to clarify associations for fruit versus vegetable intake and impact on cardiovascular outcomes. PMID:24950146

  14. Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke

    PubMed Central

    Hochmeister, Sonja; Engel, Odilo; Adzemovic, Milena Z.; Pekar, Thomas; Kendlbacher, Paul; Zeitelhofer, Manuel; Haindl, Michaela; Meisel, Andreas; Fazekas, Franz; Seifert-Held, Thomas

    2016-01-01

    Objectives From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. Methods In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. Results Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. Conclusions LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections. PMID:27152948

  15. Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.

    2009-02-01

    Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.

  16. Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with ischemic stroke in the Eastern Chinese Han population.

    PubMed

    Lv, Q-Q; Lu, J; Sun, H; Zhang, J-S

    2015-01-01

    The association between the MTHFR genetic polymorphism and ischemic stroke has been reported by a number of investigators. However, the results have been controversial and conflicting. The aim of this study was to explore the association between the MTHFR variants C677T and A1298C and the risk of ischemic stroke in an Eastern Chinese Han population. A total of 199 patients with ischemic stroke and 241 controls were recruited. Genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using the Taqman 7900HT Sequence Detection System. The overall estimates (odds ratio: OR) for the allele (C) and genotype (AC+CC) of the A1298C polymorphism were 1.57 [95% confidence interval (CI) = 1.16-2.10], and 2.36 (95%CI = 1.39-4.00), respectively, establishing significant association of the MTHFR A1298C polymorphism with ischemic stroke. In contrast, there were no statistically significant differences compared to controls between MTHFR C677T polymorphic variants in the association ischemic stroke risk. Furthermore, haplotype-based analysis demonstrated that compared with the C-677-A-1298 haplotype, the C-677-C-1298 and T-677-C-1298 haplotypes showed significant increased risk of ischemic stroke (OR = 1.56; 95%CI = 1.07- 2.2; P = 0.02; OR = 1.76; 95%CI = 1.17-2.65; P < 0.01, respectively). We concluded that the A1298C polymorphism and the haplotypes C-677-C-1298 and T-677-C-1298 in MTHFR might modulate the risk of ischemic stroke in the Eastern Chinese Han population. PMID:25966188

  17. Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011

    PubMed Central

    Gaui, Eduardo Nagib; de Oliveira, Gláucia Maria Moraes; Klein, Carlos Henrique

    2014-01-01

    Background Circulatory system diseases are the first cause of death in Brazil. Objective To analyze the evolution of mortality caused by heart failure, by ischemic heart diseases and by ill-defined causes, as well as their possible relations, in Brazil and in the geoeconomic regions of the country (North, Northeast, Center-West, South and Southeast), from 1996 to 2011. Methods Data were obtained from DATASUS and death declaration records with codes I20 and I24 for acute ischemic diseases, I25 for chronic ischemic diseases, and I50 for heart failure, and codes in chapter XIII for ill-defined causes, according to geoeconomic regions of Brazil, from 1996 to 2011. Results Mortality rates due to heart failure declined in Brazil and its regions, except for the North and the Northeast. Mortality rates due to acute ischemic heart diseases increased in the North and Northeast regions, especially from 2005 on; they remained stable in the Center-West region; and decreased in the South and in the Southeast. Mortality due to chronic ischemic heart diseases decreased in Brazil and in the Center-West, South and Southeast regions, and had little variation in the North and in the Northeast. The highest mortality rates due to ill-defined causes occurred in the Northeast until 2005. Conclusions Mortality due to heart failure is decreasing in Brazil and in all of its geoeconomic regions. The temporal evolution of mortality caused by ischemic heart diseases was similar to that of heart failure. The decreasing number of deaths due to ill-defined causes may represent the improvement in the quality of information about mortality in Brazil. The evolution of acute ischemic heart diseases ranged according to regions, being possibly confused with the differential evolution of ill-defined causes. PMID:25004417

  18. Sitagliptin After Ischemic Stroke in Type 2 Diabetic Patients: A Nationwide Cohort Study

    PubMed Central

    Chen, Dong-Yi; Wang, Szu-Heng; Mao, Chun-Tai; Tsai, Ming-Lung; Lin, Yu-Sheng; Su, Feng-Chieh; Chou, Chung-Chuan; Wen, Ming-Shien; Wang, Chun-Chieh; Hsieh, I-Chang; Hung, Kuo-Chun; Cherng, Wen-Jin; Chen, Tien-Hsing

    2015-01-01

    Abstract The cerebrovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) with ischemic stroke remains uncertain. The aim of this study was to assess the efficacy and safety of sitagliptin in patients with T2DM with recent ischemic stroke. We analyzed data from the Taiwan National Health Insurance Research Database between March 1, 2009, and December 31, 2011. Ischemic stroke patients were identified from individuals with T2DM. Patients who received sitagliptin were compared with those who did not to evaluate the cardiovascular safety and efficacy of sitagliptin. The primary outcome was a composite of ischemic stroke, myocardial infarction, or cardiovascular death. A total of 5145 type 2 diabetic patients with ischemic stroke met our inclusion criteria and were followed for up to 2.83 years (mean, 1.17 years). Overall, 1715 patients (33.3%) received sitagliptin and 3430 patients (66.7%) did not. The primary composite outcome occurred in 190 patients in the sitagliptin group (11.1%) and in 370 patients in the comparison group (10.8%) (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.85–1.21). Patients treated with sitagliptin had a similar risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality with an HR of 0.95 (95% CI, 0.78–1.16, P = 0.612), 1.07 (95% CI, 0.55–2.11, P = 0.834), and 1.00 (95% CI, 0.82–1.22, P = 0.989), respectively, compared with patients not treated with sitagliptin. Treatment with sitagliptin in type 2 diabetic patients with recent ischemic stroke was not associated with increased or decreased risks of adverse cerebrovascular outcomes. PMID:26181549

  19. Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population

    PubMed Central

    Yoo, Seung Don; Yun, Dong Hwan; Kim, Hee-Sang; Kim, Su Kang; Kim, Dong Hwan; Chon, Jinmann; Je, Goun; Kim, Yoon-Seong; Chung, Joo-Ho; Chung, Seung Joon; Yeo, Jin Ah

    2016-01-01

    Objective To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke. Methods We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data. Results No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models. Conclusion These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population. PMID:26949676

  20. Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.

    PubMed

    Hamatani, Yasuhiro; Iguchi, Moritake; Nakamura, Michikazu; Ohtani, Ryo; Yamashita, Yugo; Takagi, Daisuke; Unoki, Takashi; Ishii, Mitsuru; Masunaga, Nobutoyo; Ogawa, Hisashi; Hamatani, Mio; Abe, Mitsuru; Akao, Masaharu

    2016-07-01

    Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke. PMID:26219729

  1. Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart.

    PubMed

    Klevstig, Martina; Ståhlman, Marcus; Lundqvist, Annika; Scharin Täng, Margareta; Fogelstrand, Per; Adiels, Martin; Andersson, Linda; Kolesnick, Richard; Jeppsson, Anders; Borén, Jan; Levin, Malin C

    2016-04-01

    Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy. PMID:26930027

  2. Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation.

    PubMed

    Wang, Yu-Feng; Parpura, Vladimir

    2016-01-01

    Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas, associated with maladapted astrocytic plasticity. The astrocytic plasticity includes both morphological and functional plasticity. The former involves a reactive gliosis and the subsequent glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K(+) and glutamate, as well as the integrity of the blood-brain barrier (BBB). The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein (GFAP) and water channel protein aquaporin 4 (AQP4) to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the BBB. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the BBB, but also leads to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation. PMID:27242440

  3. Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke

    PubMed Central

    Zhao, Xu; Yu, Yue; Xu, Wenlong; Dong, Lei; Wang, Yuan; Gao, Bing; Li, Guangyu; Zhang, Wentao

    2016-01-01

    Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage. PMID:27043525

  4. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke

    PubMed Central

    Lakhan, Shaheen E.; Kirchgessner, Annette; Tepper, Deborah; Leonard, Aidan

    2013-01-01

    Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined. PMID:23565108

  5. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine

    PubMed Central

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-01-01

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837

  6. Genetic Ablation of Pannexin1 Protects Retinal Neurons from Ischemic Injury

    PubMed Central

    Dvoriantchikova, Galina; Ivanov, Dmitry; Barakat, David; Grinberg, Alexander; Wen, Rong; Slepak, Vladlen Z.; Shestopalov, Valery I.

    2012-01-01

    Pannexin1 (Panx1) forms large nonselective membrane channel that is implicated in paracrine and inflammatory signaling. In vitro experiments suggested that Panx1 could play a key role in ischemic death of hippocampal neurons. Since retinal ganglion cells (RGCs) express high levels of Panx1 and are susceptible to ischemic induced injury, we hypothesized that Panx1 contributes to rapid and selective loss of these neurons in ischemia. To test this hypothesis, we induced experimental retinal ischemia followed by reperfusion in live animals with the Panx1 channel genetically ablated either in the entire mouse (Panx1 KO), or only in neurons using the conditional knockout (Panx1 CKO) technology. Here we report that two distinct neurotoxic processes are induced in RGCs by ischemia in the wild type mice but are inactivated in Panx1KO and Panx1 CKO animals. First, the post-ischemic permeation of RGC plasma membranes is suppressed, as assessed by dye transfer and calcium imaging assays ex vivo and in vitro. Second, the inflammasome-mediated activation of caspase-1 and the production of interleukin-1β in the Panx1 KO retinas are inhibited. Our findings indicate that post-ischemic neurotoxicity in the retina is mediated by previously uncharacterized pathways, which involve neuronal Panx1 and are intrinsic to RGCs. Thus, our work presents the in vivo evidence for neurotoxicity elicited by neuronal Panx1, and identifies this channel as a new therapeutic target in ischemic pathologies. PMID:22384122

  7. Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Caughey, Melissa C.; Loehr, Laura R.; Key, Nigel S.; Derebail, Vimal K.; Gottesman, Rebecca F.; Kshirsagar, Abhijit V.; Grove, Megan L.; Heiss, Gerardo

    2014-01-01

    Background and Purpose Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. Methods A population-based sample of African Americans (N=3,497, mean age=54, female=62%) was followed from 1987–2011 in the Atherosclerosis Risk in Communities Study (ARIC), contributing a total of 65,371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A (HbAA). Models were adjusted for age, sex, smoking, diabetes, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. Results SCT was identified in 223 (6.4%) participants. Over a median follow up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than HbAA (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0 – 2.0), and an incidence rate difference amounting to 1.9 (0.4 – 3.8) extra strokes per 1000 person-years. Conclusion We observed an increased risk of ischemic stroke in African Americans with SCT. Further investigation of the incidence and pathophysiology of stroke in SCT patients is warranted. PMID:25139879

  8. Evaluation of mean diffusion and kurtosis MRI mismatch in subacute ischemic stroke: Comparison with NIHSS score.

    PubMed

    Guo, Yue-Lin; Zhang, Zhong-Ping; Zhang, Gui-Shan; Kong, Ling-Mei; Rao, Hai-Bing; Chen, Wei; Wang, Guang-Wen; Shen, Zhi-Wei; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-08-01

    Neurological deterioration (ND) is a devastating complication following ischemic stroke. This study aimed to identify the differences in lesion characteristics in subacute ischemic stroke patients with and without ND using diffusional kurtosis imaging (DKI), as well as to confirm the responsible lesions that may lead to ND, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Seventy-nine patients with subacute cerebral infarction were allocated to the ND (-) and ND (+) groups according to the NIHSS score and lesion number. The mean diffusion (MD) lesions were significantly larger than the mean kurtosis (MK) deficits in the ND (+) group (P<0.05); however, there was no significant difference in the ND (-) group (P>0.05). The MD and MK in the lesion recovered to normal levels over time; however, the recovery trends in the ND (+) group were substantially slower than the ND (-) group. The differences between the two groups were only significant regarding the MK (p<0.05). Furthermore, multiple infarction lesions exhibited good consistency in the ND (-) group, but were non-homogeneous in the ND (+) group. To the best of our knowledge, this is the first study to demonstrate that a significant MD/MK mismatch and heterogeneity of multiple ischemic lesions on MK in subacute ischemic stroke may represent a new expansion of an ischemic lesion or acute reinfarction, which is closely related to ND. PMID:27208488

  9. Serum C-reactive protein level as a biomarker for differentiation of ischemic from hemorrhagic stroke.

    PubMed

    Roudbary, Seyed Ali; Saadat, Farshid; Forghanparast, Kambiz; Sohrabnejad, Reza

    2011-01-01

    Cerebrovascular accidents rank first in the frequency and importance among all neurological disease. Although a number of studies had shown increased level of the high sensitive C-reactive protein (hs-CRP) in patients with ischemic stroke, the association of increased hs-CRP with various type of stroke especially the assessment hs-CRP level in ischemic and hemorrhagic stroke have not been investigated. In the present study, we assessed the concentration of hs-CRP in patients with documented ischemic and hemorrhagic stroke in the first 24 hours of the onset of symptoms. Thirty-two patients with Ischemic and hemorrhagic stroke were evaluated at neurology department of Poursina Hospital. The presence of baseline vascular risk factors, including hypertension, diabetes mellitus, hypercholesterolemia, obesity, and smoking, was determined. The blood samples were then collected and routine hematology and biochemistry tests were done. hs-CRP levels were determined using a highly sensitive immunonephelometric method. In this cross sectional study, the age of patient varied from 45-85 years (Mean 70.9 ± 9.4). Serum level of hs-CRP in Ischemic patients were 18.92 ± 11.28 and in hemorrhagic group was 2.65 ± 1.7. This relationship was statistically significant (P<0.0001). It might be concluded that hs-CRP might be considered as a usefully adjunct method for the initial diagnosis of the type of stroke. PMID:21681701

  10. Effects of passive smoking on ischemic heart disease mortality of nonsmokers. A prospective study

    SciTech Connect

    Garland, C.; Barrett-Connor, E.; Suarez, L.; Criqui, M.H.; Wingard, D.L.

    1985-05-01

    The mortality attributable to ischemic heart disease as a result of cigarette smoking is greater of a community of older adults in southern California, the authors tested the hypothesis that nonsmoking women exposed to their husband's cigarette smoke would have an elevated risk of fatal ischemic heart disease. Married women aged 50-79 years who had never smoked cigarettes (n = 695) were classified according to the husband's self-reported smoking status at entry into the study: never, former, or current smoker. After 10 years, nonsmoking wives of current or former cigarette smokers had a higher total (p less than or equal to 0.05) and age-adjusted (p less than or equal to 0.10) death rate from ischemic heart disease than women whose husbands never smoked. After adjustment for differences in risk factors for heart disease, the relative risk for death from ischemic heart disease in nonsmoking women married to current or former cigarette smokers was 14.9 (p less than or equal to 0.10). These data are compatible with the hypothesis that passive cigarette smoking carries an excess risk of fatal ischemic heart disease.

  11. Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload.

    PubMed

    Zhao, Yixiu; Gao, Feng; Zhang, Yong; Wang, Hongtao; Zhu, Jiuxin; Chang, Liping; Du, Zhimin; Zhang, Yan

    2016-06-01

    Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload. PMID:27122298

  12. Myocardial ischemic post-conditioning attenuates ischemia reperfusion injury via PTEN/Akt signal pathway

    PubMed Central

    Li, Chun-Mei; Shen, Shu-Wen; Wang, Tao; Zhang, Xing-Hua

    2015-01-01

    Objectives: To investigate whether myocardial ischemic post-conditioning attenuates ischemia reperfusion injury via PTEN/Akt signal pathway. Design: Forty-five male Sprague-Dawley rats were randomly divided into three groups: Sham, Ischemia reperfusion (I/R) and Ischemic post-conditioning (IPost) group. After the experiment finished, myocardial infarction area was examined. Serum creatine phosphokinase and lactate dehydrogenase activity were detected at baseline and the end of reperfusion. The protein levels of PTEN, Akt, p-Akt, Bax and Bcl-2 were measured by Western blot method. Results: Myocardial infarct size was significantly reduced in IPost as compared to I/R. Results were confirmed by serum creatine phosphokinase and lactate dehydrogenase activity. In addition, PTEN and Bax protein expression were inhibited and the p-Akt and bcl-2 protein expression were enhanced in IPost compared with I/R (P < 0.05). At the same time, the ratio of Bax and Bcl-2 was decreased in IPost (P < 0.05). However, ischemic post conditioning did not affect the total Akt level (P > 0.05). Conclusions: We confirmed that ischemic post-conditioning protects the heart against reperfusion injury. It is important that we demonstrated that the cardioprotective effect of ischemic post-conditioning was involved in the inhibition of PTEN, activation of the PI3K/Akt pathway and reduction of the cardiomyocyte apoptosis. PMID:26629079

  13. Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke.

    PubMed

    Zhao, Xu; Yu, Yue; Xu, Wenlong; Dong, Lei; Wang, Yuan; Gao, Bing; Li, Guangyu; Zhang, Wentao

    2016-01-01

    Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage. PMID:27043525

  14. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage

    PubMed Central

    Kim, Kyeong-A; Akram, Muhammad; Shin, Young-Jun; Kim, Eun-Sun; Yu, Seong Woon; Majid, Arshad; Bae, Ok-Nam

    2014-01-01

    Background and Purpose Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide which has robust neuroprotective activity against ischemic brain damage. Methods We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Results Autophagic pathways such as reduction of phosphorylated mTOR/p70S6K and the conversion of LC3-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Conclusion Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection, and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences. PMID:24938837

  15. Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation

    PubMed Central

    Wang, Yu-Feng; Parpura, Vladimir

    2016-01-01

    Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas, associated with maladapted astrocytic plasticity. The astrocytic plasticity includes both morphological and functional plasticity. The former involves a reactive gliosis and the subsequent glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K+ and glutamate, as well as the integrity of the blood-brain barrier (BBB). The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein (GFAP) and water channel protein aquaporin 4 (AQP4) to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the BBB. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the BBB, but also leads to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation. PMID:27242440

  16. The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future

    PubMed Central

    L.L.Yeo, Leonard; Sharma, Vijay K

    2013-01-01

    Ischemic stroke is one of the major causes of mortality and long-term disability. In the recent past, only very few treatment options were available and a considerable proportion of stroke survivors remained permanently disabled. However, over the last 2 decades rapid advances in acute stroke care have resulted in a corresponding improvement in mortality rates and functional outcomes. In this review, we describe the evolution of systemic thrombolytic agents and various interventional devices, their current status as well as some of the future prospects. We reviewed literature pertaining to acute ischemic stroke reperfusion treatment. We explored the current accepted treatment strategies to attain cerebral reperfusion via intravenous modalities and compare and contrast them within the boundaries of their clinical trials. Subsequently we reviewed the trials for interventional devices for acute ischemic stroke, categorizing them into thrombectomy devices, aspiration devices, clot disruption devices and thrombus entrapment devices. Finally we surveyed several of the alternative reperfusion strategies available. We also shed some light on the controversies surrounding the current strategies of treatment of acute ischemic stroke. Acute invasive interventional strategies continue to improve along with the noninvasive modalities. Both approaches appear promising. We conducted a comprehensive chronological review of the existing treatments as well as upcoming remedies for acute ischemic stroke. PMID:23864913

  17. Semi-rigid penile prosthesis as a salvage management of idiopathic ischemic stuttering priapism

    PubMed Central

    Faddan, Amr A; Aksenov, Alexey V; Naumann, Carsten M; Jünemann, Klaus P; Osmonov, Daniar K

    2015-01-01

    Introduction Priapism is the persistent erection resulting from dysfunction of the mechanisms that regulate penile swelling, stiffness, and sagging. It is a full or partial erection that persists for a period more than 4 hours beyond sexual stimulation and/or orgasm or is unrelated to sexual stimulation. Ischemic priapism should be managed in a step-by-step fashion. Objective To demonstrate step-by-step management of stuttering refractory ischemic priapism. We report a case of stuttering refractory ischemic priapism. Moreover, we reviewed different approaches to priapism management in the literature. Case presentation A 53-year-old male presented with a painful erection of 29 hours’ duration, probably caused by consumption of alcohol. The penile blood gas showed a pH of 7.08, PCO2 of 75 mmHg and PO2 of 39 mmHg. Aspiration was followed by irrigation of an α-adrenergic, Winter and T-shunt operations were preformed, and finally a semi-rigid penile prosthesis was implanted to overcome the refractory stuttering ischemic priapism. Conclusion In case of stuttering refractory ischemic priapism, immediate implantation of a penile prosthesis is a simple and effective procedure that manages both the acute episode and the inevitable erectile dysfunction that would otherwise occur, while preserving penile length. PMID:26380229

  18. Isolation and Flow Cytometric Analysis of Immune Cells from the Ischemic Mouse Brain

    PubMed Central

    Boltze, Johannes; Wagner, Daniel-Christoph; Weise, Gesa

    2016-01-01

    Ischemic stroke initiates a robust inflammatory response that starts in the intravascular compartment and involves rapid activation of brain resident cells. A key mechanism of this inflammatory response is the migration of circulating immune cells to the ischemic brain facilitated by chemokine release and increased endothelial adhesion molecule expression. Brain-invading leukocytes are well-known contributing to early-stage secondary ischemic injury, but their significance for the termination of inflammation and later brain repair has only recently been noticed. Here, a simple protocol for the efficient isolation of immune cells from the ischemic mouse brain is provided. After transcardial perfusion, brain hemispheres are dissected and mechanically dissociated. Enzymatic digestion with Liberase is followed by density gradient (such as Percoll) centrifugation to remove myelin and cell debris. One major advantage of this protocol is the single-layer density gradient procedure which does not require time-consuming preparation of gradients and can be reliably performed. The approach yields highly reproducible cell counts per brain hemisphere and allows for measuring several flow cytometry panels in one biological replicate. Phenotypic characterization and quantification of brain-invading leukocytes after experimental stroke may contribute to a better understanding of their multifaceted roles in ischemic injury and repair. PMID:26967380

  19. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine.

    PubMed

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-01-01

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837

  20. Elevation of troponin I in acute ischemic stroke

    PubMed Central

    Su, Yu-Chin; Huang, Kuo-Feng; Yang, Fu-Yi

    2016-01-01

    Background. Cardiac morbidities account for 20% of deaths after ischemic stroke and is the second commonest cause of death in acute stroke population. Elevation of cardiac troponin has been regarded as a prognostic biomarker of poor outcome in patients with acute stroke. Methods. This retrospective study enrolled 871 patients with acute ischemic stroke from August 2010 to March 2015. Data included vital signs, laboratory parameters collected in the emergency department, and clinical features during hospitalization. National Institutes of Health Stroke Scale (NIHSS), Barthel index, and modified Rankin Scale (mRS) were used to assess stroke severity and outcome. Results. Elevated troponin I (TnI) > 0.01 µg/L was observed in 146 (16.8%) patients. Comparing to patients with normal TnI, patients with elevated TnI were older (median age 77.6 years vs. 73.8 years), had higher median heart rates (80 bpm vs. 78 bpm), higher median white blood cells (8.40 vs. 7.50 1,000/m3) and creatinine levels (1.40 mg/dL vs. 1.10 mg/dL), lower median hemoglobin (13.0 g/dL vs. 13.7 g/dL) and hematocrit (39% vs. 40%) levels, higher median NIHSS scores on admission (11 vs. 4) and at discharge (8 vs. 3), higher median mRS scores (4 vs3) but lower Barthel index scores (20 vs. 75) at discharge (p < 0.001). Multivariate analysis revealed that age ≥ 76 years (OR 2.25, CI [1.59–3.18]), heart rate ≥ 82 bpm (OR 1.47, CI [1.05–2.05]), evidence of clinical deterioration (OR 9.45, CI [4.27–20.94]), NIHSS score ≥ 12 on admission (OR 19.52, CI [9.59–39.73]), and abnormal TnI (OR 1.98, CI [1.18–3.33]) were associated with poor outcome. Significant factors for in-hospital mortality included male gender (OR 3.69, CI [1.45–9.44]), evidence of clinical deterioration (OR 10.78, CI [4.59–25.33]), NIHSS score ≥ 12 on admission (OR 8.08, CI [3.04–21.48]), and elevated TnI level (OR 5.59, CI [2.36–13.27]). C-statistics revealed that abnormal TnI improved the predictive power of both poor

  1. Effects of ischemic stroke on dynamics of cerebral autoregulation

    NASA Astrophysics Data System (ADS)

    Chen, Zhi; Ivanov, Plamen Ch; Hu, Kun; Stanley, Eugene; Novak, Vera

    2004-03-01

    Cerebral vasoregulation involves several complex mechanisms adapting blood flow to fluctuations of systemic blood pressure (BP). Autonomic BP and metabolic vasoregulation are impaired after stroke and cerebral blood flow depends on systemic BP. To probe the mechanisms of cerebral autoregulation we study levels of nonlinear synchronization between cerebral blood flow velocity (BFV) and peripheral BP. We quantify the instantaneous phase of each signal employing analytic signal approach and Hilbert transform. As a marker of synchronization, we introduce a measure of cross-correlation between the instantaneous phase increments of the BFV and BP signals at different time lags. We have studied 12 subjects with minor chronic ischemic stroke and 11 matched normotensive controls (age<65years). BFV and BP of these subjects are continuously recorded during supine baseline, head-up tilt, hyperventilation and CO2 rebreathing. For control subjects we find significant synchronization between cerebral BFV and peripheral BP only for short time lags of up to 5-6 seconds, suggesting a rapid return to a steady cerebral blood flow after initial blood pressure perturbations. In contrast, for stroke subjects BFV/BP we find enhanced synchronization over longer time lags of up to 20 seconds, suggesting entrainment of cerebral blood flow velocity by slow vasomotor rhythms. These findings suggest that cerebral vasoregulation is impaired and cerebral blood flow follows the fluctuations of systemic BP in a synchronous manner. Our analysis shows that cerebral autoregulation is impaired in 10 out of the 12 stroke subjects, which is typically difficult to diagnose with conventional methods. Thus, our novel synchronization approach offers a new tool sensitive for evaluation of changes in the dynamics of cerebral autoregulation under stroke.

  2. Statins in Acute Ischemic Stroke: A Systematic Review

    PubMed Central

    Hong, Keun-Sik; Lee, Ji Sung

    2015-01-01

    Background and Purpose Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS. Methods From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates. Results In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). Conclusions The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence. PMID:26437994

  3. Establishment of a new animal model for ischemic lumbar vertebrae

    PubMed Central

    Hou, Changlong; Tan, Guosheng; Zhuang, Wenquan; Yang, Jianyong

    2015-01-01

    Degeneration and ischemia of lumbar intervertebral disc has become a more and more important issue for elder people. However the mechanism for this is still known, largely due to a lack of a suitable animal model. In this study, we constructed a new animal model for the study of ischemic lumbar vertebrae. 42 New Zealand white rabbits were chosen for the study. For each rabbit, two vertebrae were used. L5 was set as the experimental group and L4 was set as the control group. Percutaneous lumbar puncture needles were applied in vertebrae adjacent to endplate for L5 and L4. For L4 1 ml saline was injected and for L5 1 ml pingyangmycin (2 mg/mL) was used. 1, 2, 3, 4, 5 weeks; 2 and 3 months after surgery, 6 rabbits at each time point were randomly chosen and underwent MRI, pathological test. The results in L5 and L4 were compared. Another 6 rabbits were used for DSA (Digital Subtraction Angiography) and vascular cast to study the length and diameters of the branches of lumbar artery. It was identified that since the third week, slightly hyperintense signal on T2-weighted image (T2WI) and fat-suppression T2-weighted image (FS T2WI) were detected. Lumbar vertebrae damage could be identified since the fourth week. Results of MRI and the size of pathological area were positively related (r=0.965, P<0.05). DSA and vascular cast could both clearly show the third level branches of lumbar artery. Our study suggested that injection of pingyangmycin via percutaneous lumbar needle could successfully induce ischemia in lumbar endplate. This method had little trauma, required a simple operation process and is highly repetitive. Besides, by vascular cast, the most important source of blood supply is the media branch of the lumbar artery. This branch could be a new therapy pathway for the degeneration of lumbar vertebrae. PMID:26379856

  4. Assessing the Global Burden of Ischemic Heart Disease

    PubMed Central

    Moran, Andrew E.; Oliver, John T.; Mirzaie, Masoud; Forouzanfar, Mohammad H.; Chilov, Marina; Anderson, Laurie; Morrison, Janina L.; Khan, Aayla; Zhang, Nasen; Haynes, Norrisa; Tran, Jackie; Murphy, Adrianna; DeGennaro, Vincent; Roth, Gregory; Zhao, Dong; Peer, Nasheeta; Pichon-Riviere, Andres; Rubinstein, Adolfo; Pogosova, Nana; Prabhakaran, Dorairaj; Naghavi, Mohsen; Ezzati, Majid; Mensah, George A.

    2012-01-01

    BACKGROUND Ischemic heart disease (IHD) is the leading cause of death worldwide. The GBD (Global Burden of Disease, Injuries, and Risk Factors) study (GBD 2010 Study) conducted a systematic review of IHD epidemiology literature from 1980 to 2008 to inform estimates of the burden on IHD in 21 world regions in 1990 and 2010. METHODS The disease model of IHD for the GBD 2010 Study included IHD death and 3 sequelae: myocardial infarction, heart failure, and angina pectoris. Medline, EMBASE, and LILACS were searched for IHD epidemiology studies in GBD high-income and low- and middle-income regions published between 1980 and 2008 using a systematic protocol validated by regional IHD experts. Data from included studies were supplemented with unpublished data from selected high-quality surveillance and survey studies. The epidemiologic parameters of interest were incidence, prevalence, case fatality, and mortality. RESULTS Literature searches yielded 40,205 unique papers, of which 1,801 met initial screening criteria. Upon detailed review of full text papers, 137 published studies were included. Unpublished data were obtained from 24 additional studies. Data were sufficient for high-income regions, but missing or sparse in many low- and middle-income regions, particularly Sub-Saharan Africa. CONCLUSIONS A systematic review for the GBD 2010 Study provided IHD epidemiology estimates for most world regions, but highlighted the lack of information about IHD in Sub-Saharan Africa and other low-income regions. More complete knowledge of the global burden of IHD will require improved IHD surveillance programs in all world regions. PMID:23682350

  5. Effects of ischemic preconditioning on short-duration cycling performance.

    PubMed

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Salvador, Amadeo Félix; Caputo, Fabrizio

    2016-08-01

    It has been demonstrated that ischemic preconditioning (IPC) improves endurance performance. However, the potential benefits during anaerobic events and the mechanism(s) underlying these benefits remain unclear. Fifteen recreational cyclists were assessed to evaluate the effects of IPC of the upper thighs on anaerobic performance, skeletal muscle activation, and metabolic responses during a 60-s sprint performance. After an incremental test and a familiarization visit, subjects were randomly submitted in visits 3 and 4 to a performance protocol preceded by intermittent bilateral cuff inflation (4 × (5 min of blood flow restriction + 5 min reperfusion)) at either 220 mm Hg (IPC) or 20 mm Hg (control). To increase data reliability, each intervention was replicated, which was also in a random manner. In addition to the mean power output, the pulmonary oxygen uptake, blood lactate kinetics, and quadriceps electromyograms (EMGs) were analyzed during performance and throughout 45 min of passive recovery. After IPC, performance was improved by 2.1% compared with control (95% confidence intervals of 0.8% to 3.3%, P = 0.001), followed by increases in (i) the accumulated oxygen deficit, (ii) the amplitude of blood lactate kinetics, (iii) the total amount of oxygen consumed during recovery, and (iv) the overall EMG amplitude (P < 0.05). In addition, the ratio between EMG and power output was higher during the final third of performance after IPC (P < 0.05). These results suggest an increased skeletal muscle activation and a higher anaerobic contribution as the ultimate responses of IPC on short-term exercise performance. PMID:27404398

  6. Trans-system mechanisms against ischemic myocardial injury.

    PubMed

    Liu, Shu Q; Ma, Xin-Liang; Qin, Gangjian; Liu, Qingping; Li, Yan-Chun; Wu, Yu H

    2015-01-01

    A mammalian organism possesses a hierarchy of naturally evolved protective mechanisms against ischemic myocardial injury at the molecular, cellular, and organ levels. These mechanisms comprise regional protective processes, including upregulation and secretion of paracrine cell-survival factors, inflammation, angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration. There are also interactive protective processes between the injured heart, circulation, and selected remote organs, defined as trans-system protective mechanisms, including upregulation and secretion of endocrine cell-survival factors from the liver and adipose tissue as well as mobilization of bone marrow, splenic, and hepatic cells to the injury site to mediate myocardial protection and repair. The injured heart and activated remote organs exploit molecular and cellular processes, including signal transduction, gene expression, cell proliferation, differentiation, migration, mobilization, and/or extracellular matrix production, to establish protective mechanisms. Both regional and trans-system cardioprotective mechanisms are mediated by paracrine and endocrine messengers and act in coordination and synergy to maximize the protective effect, minimize myocardial infarction, and improve myocardial function, ensuring the survival and timely repair of the injured heart. The concept of the trans-system protective mechanisms may be generalized to other organ systems-injury in one organ may initiate regional as well as trans-system protective responses, thereby minimizing injury and ensuring the survival of the entire organism. Selected trans-system processes may serve as core protective mechanisms that can be exploited by selected organs in injury. These naturally evolved protective mechanisms are the foundation for developing protective strategies for myocardial infarction and injury-induced disorders in other organ systems. PMID:25589268

  7. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models

    PubMed Central

    Bernstein, Steven L.; Johnson, Mary A.; Miller, Neil R.

    2011-01-01

    Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, and the power of a `vertically integrated' multi-species approach can help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may

  8. Blueberry-Enriched Diet Protects Rat Heart from Ischemic Damage

    PubMed Central

    Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara; Juhaszova, Magdalena; Sollott, Steven J.; Joseph, James A.; Ingram, Donald K.; Talan, Mark

    2009-01-01

    Objectives to assess the cardioprotective properties of a blueberry enriched diet (BD). Background Reactive oxygen species (ROS) play a major role in ischemia-related myocardial injury. The attempts to use synthetic antioxidants to block the detrimental effects of ROS have produced mixed or negative results precipitating the interest in natural products. Blueberries are readily available product with the highest antioxidant capacity among fruits and vegetables. Methods and Results Following 3-mo of BD or a regular control diet (CD), the threshold for mitochondrial permeability transition (tMPT) was measured in isolated cardiomyocytes obtained from young male Fischer-344 rats. Compared to CD, BD resulted in a 24% increase (p<0.001) of ROS indexed tMPT. The remaining animals were subjected to a permanent ligation of the left descending coronary artery. 24 hrs later resulting myocardial infarction (MI) in rats on BD was 22% less than in CD rats (p<0.01). Significantly less TUNEL(+) cardiomyocytes (2% vs 9%) and 40% less inflammation cells were observed in the myocardial area at risk of BD compared to CD rats (p<0.01). In the subgroup of rats, after coronary ligation the original diet was either continued or switched to the opposite one, and cardiac remodeling and MI expansion were followed by serial echocardiography for 10 weeks. Measurements suggested that continuation of BD or its withdrawal after MI attenuated or accelerated rates of post MI cardiac remodeling and MI expansion. Conclusion A blueberry-enriched diet protected the myocardium from induced ischemic damage and demonstrated the potential to attenuate the development of post MI chronic heart failure. PMID:19536295

  9. [Vertebrobasilar transient ischemic attacks in young and middle aged patients].

    PubMed

    Beliavskiĭ, N N; Likhachev, S A; Varenik, T N; Demarin, V

    2008-01-01

    A complex clinical, neurological, laboratory, ultrasound and neuroimaging examination of 70 patients, aged 31-59 years, suffering from vertebrobasilar transient ischemic attack (TIA) was carried out in order to determine clinical and pathogenetic peculiarities of the disease in young and middle aged patients. The hemodynamically significant atherosclerotic lesion of the large cerebral arteries (LCA) as a cause of TIA was observed more rarely in the young and middle age groups than in elderly and aged people. Heart valves lesion was the main cause of cerebral cardioembolism in young and middle aged patients with TIA. A greater number of cases with other established causes of the disease (dissections, kinking of vertebral arteries, hemorheological microocclusion) were revealed. An undetermined pathogenesis of the disease mostly due to the inability to choose the main pathogenetic mechanism out of other potential mechanisms, e.g., the association of arterial hypertension with kinking, the hypoplasia or anomaly of the entrance of vertebral artery into the transverse channel, was observed in these groups more often than in elderly and aged people. The clinical picture of TIA in young and middle aged patients with hemodynamically significant atherosclerotic lesion of LCA had the highest similarity with that in elderly and aged ones. In case of cardioembolic pathogenesis, it was characterized by the markedly less severe signs of the disease and in case of the disease due to isolated arterial hypertension--by the lower rate of vascular white matter abnormalities on neuroimaging. A relatively higher rate of symptoms attributed to the manifestation of hypertensive crisis during the attack was observed in young and middle aged patients with TIA due to isolated arterial hypertension comparing with other pathogenetic variants of the disease. The clinical picture of TIA due to other established causes was depended on the main pathogenetic mechanism of the disease. PMID:19431240

  10. Hyperinsulinemia improves ischemic LV function in insulin resistant subjects

    PubMed Central

    2010-01-01

    Background Glucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR. Methods 24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC. Results HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR. Conclusions Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy. PMID:20576156

  11. Ischemic preconditioning reduces hemodynamic response during metaboreflex activation.

    PubMed

    Mulliri, Gabriele; Sainas, Gianmarco; Magnani, Sara; Palazzolo, Girolamo; Milia, Nicola; Orrù, Andrea; Roberto, Silvana; Marongiu, Elisabetta; Milia, Raffaele; Crisafulli, Antonio

    2016-05-01

    Ischemic preconditioning (IP) has been shown to improve exercise performance and to delay fatigue. However, the precise mechanisms through which IP operates remain elusive. It has been hypothesized that IP lowers the sensation of fatigue by reducing the discharge of group III and IV nerve endings, which also regulate hemodynamics during the metaboreflex. We hypothesized that IP reduces the blood pressure response during the metaboreflex. Fourteen healthy males (age between 25 and 48 yr) participated in this study. They underwent the following randomly assigned protocol: postexercise muscle ischemia (PEMI) test, during which the metaboreflex was elicited after dynamic handgrip; control exercise recovery session (CER) test; and PEMI after IP (IP-PEMI) test. IP was obtained by occluding forearm circulation for three cycles of 5 min spaced by 5 min of reperfusion. Hemodynamics were evaluated by echocardiography and impedance cardiography. The main results were that after IP the mean arterial pressure response was reduced compared with the PEMI test (means ± SD +3.37 ± 6.41 vs. +9.16 ± 7.09 mmHg, respectively). This was the consequence of an impaired venous return that impaired the stroke volume during the IP-PEMI more than during the PEMI test (-1.43 ± 15.35 vs. +10.28 ± 10.479 ml, respectively). It was concluded that during the metaboreflex, IP affects hemodynamics mainly because it impairs the capacity to augment venous return and to recruit the cardiac preload reserve. It was hypothesized that this is the consequence of an increased nitric oxide production, which reduces the possibility to constrict venous capacity vessels. PMID:26936782

  12. End-ischemic reconditioning of liver allografts: Controlling the rewarming.

    PubMed

    Hoyer, Dieter Paul; Paul, Andreas; Luer, Sebastian; Reis, Henning; Efferz, Patrik; Minor, Thomas

    2016-09-01

    Different nonhypothermic preservation modalities have shown beneficial effects in liver transplantation models. This study compares controlled oxygenated rewarming (COR) to normothermic machine perfusion (NMP) to resuscitate liver grafts following cold storage (CS). Porcine livers were preserved for 18 hours by CS. Before reperfusion, the grafts were put on a machine perfusion device (Liver Assist) for 3 hours and were randomly assigned to COR (n = 6) or NMP (n = 5) and compared to standard CS. COR was carried out with the new Custodiol-N solution, slowly increasing temperature from 8 °C to 20 °C during the first 90 minutes. NMP was carried out with diluted autologous blood at 37 °C for 3 hours. In both cases, the perfusate was oxygenated to partial pressure of oxygen > 500 mm Hg. Then liver viability was tested for 180 minutes during in vitro isolated sanguineous reperfusion. Activity of the mitochondrial caspase 9 was lower after COR. Measurement of tissue adenosine triphosphate and total adenine nucleotides at the end of the reconditioning period showed better energetic recovery after COR. COR also resulted in significantly lower enzyme leakage and higher bile production (P < 0.05) during reperfusion. This first comparison of COR and NMP as end-ischemic reconditioning modalities demonstrates superior results in terms of mitochondrial integrity resulting in better energetic recovery, less hepatocellular injury, and ultimately superior function in favor of COR. Liver Transplantation 22 1223-1230 2016 AASLD. PMID:27398813

  13. Gallstone Disease and the Risk of Ischemic Heart Disease

    PubMed Central

    Lv, Jun; Qi, Lu; Yu, Canqing; Guo, Yu; Bian, Zheng; Chen, Yiping; Yang, Ling; Shen, Jie; Wang, Shanqing; Li, Mingqiang; Liu, Yongmei; Zhang, Libo; Chen, Junshi; Chen, Zhengming; Li, Liming

    2015-01-01

    Objective Gallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD). Approach and Results We examined the association of GSD with IHD among 199,292 men and 288,081 women aged 30–79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3,431,124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10,245 incident IHD cases in men and 14,714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval [CI], 1.02–1.22) for men with GSD; the respective hazard ratio was 1.27 (95% CI, 1.20–1.34) in women and 1.23 (95% CI, 1.17–1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (P=0.009 for interaction with sex). In addition, we found the association between GSD and IHD was stronger in non-hypertensive than hypertensive women (P<0.001 for interaction). Conclusions In this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health. PMID:26272939

  14. Effects of systemic erythropoietin on ischemic wound healing in rats.

    PubMed

    Arslantaş, Mustafa Kemal; Arslantaş, Reyhan; Tozan, Emine Nur

    2015-03-01

    Results of in vivo studies have shown erythropoietin (EPO) is associated with anti-inflammatory, anti-apoptotic, and cell protective effects on wound healing. These effects are dose-dependent. The aim of this study was to evaluate whether the duration of EPO treatment affects the healing process in the ischemic wound. Forty-two (42) Sprague-Dawley rats were anesthetized, wounded with H-shaped flaps, and randomized to 2 groups; Group 1 received 400 u/kg/day EPO and Group 2 received a saline solution, both via intraperitoneal injection following the wounding. All substances were administered once daily at the same time for up to 10 days after surgery. At days 3, 5, and 10, 7 rats from each group were sacrificed. Skin samples were stained with hematoxylin/eosin, viewed under an optical microscope at 10X and 40X magnification, and analyzed by blinded investigators for re-epithelialization, neovascularization amount and maturation of granulation tissue, inflammatory cells, and ulcer healing using an evaluation scale where 0 = none; 1 = partial; 2 = complete, but immature/thin: and 4 = complete and mature. Blood hemoglobin and hematocrit levels also were measured. Data were analyzed using ANOVA one-way test (P <0.05). Hemoglobin and hematocrit levels rose while subsequent doses of EPO were administered over time, accompanied by a transient surge in healing on day 5, when differences in healing scores were significant. Flap necrosis, ulceration, and abscess were noted on post-wounding day 10 near the pedicle. The study showed EPO therapy can improve wound healing early in the post-wounding period but can reduce wound healing after post-injury treatment day 5. Further research is necessary, particularly to establish how EPO influences the microcirculation and rheology. PMID:25751848

  15. Alcohol consumption, Lewis phenotypes, and risk of ischemic heart disease

    SciTech Connect

    Hein, H.O.; Suadicani, P.; Gyntelberg, F. . Epidemiological Research Unit); Sorenson, H. . Dept. of Chemical Immunology); Hein, H.O. . Dept. of Internal Medicine)

    1993-02-13

    The authors have previously found an increased risk of ischemic heart disease (IHD) in men with the Lewis phenotype Le(a[minus]b[minus]) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. The authors have investigated whether any conventional risk factors explain the increased risk in Le(a[minus]b[minus]) men. 3,383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, the authors excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a[minus]b[minus]), alcohol was the only risk factor significantly associated with risk of IHD. There was a significant inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p=0.02), all IHD (p=0.03), and all causes of death (p=0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a[minus]b[minus]) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. The authors suggest that alcohol consumption may modify insulin resistance in Le(a[minus]b[minus]) men.

  16. Polymorphisms of IGFI contribute to the development of ischemic stroke.

    PubMed

    Kim, Hak Jae; Kim, Su Kang; Park, Hae Jeong; Chung, Joo-Ho; Chun, Jinman; Yun, Dong Hwan; Kim, Young Ock

    2012-01-01

    Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the IFG1 gene are associated with the development and clinical features of IS in a Korean population. A total of 119 patients with IS and 289 control subjects were recruited. Stroke patients were classified into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and ≥6) and the Modified Barthel Index (MBI; <60 and ≥60). Among the SNPs of the IFG1 gene, five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron), rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3' untranslated region; 3'UTR). Multiple logistic regression models were conducted to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After Bonferroni correction (p(c)), the A and G alleles of rs2162679 and rs6214 had significant differences between patients with IS and the controls [rs2162679, OR (95% CI) = 1.64 (1.17-2.31), p=0.004, p(c)=0.02; rs6214, OR (95% CI) = 1.52 (1.12-2.07), p=0.007, p(c)=0.035], respectively. However, the five selected SNPs were not related to the NIHSS and MBI scores. These results suggest that IGF1 may be associated with the development of IS. PMID:22969851

  17. Polymorphisms of IGFI contribute to the development of ischemic stroke

    PubMed Central

    KIM, HAK JAE; KIM, SU KANG; PARK, HAE JEONG; CHUNG, JOO-HO; CHUN, JINMAN; YUN, DONG HWAN; KIM, YOUNG OCK

    2012-01-01

    Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the IFG1 gene are associated with the development and clinical features of IS in a Korean population. A total of 119 patients with IS and 289 control subjects were recruited. Stroke patients were classified into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and ≥6) and the Modified Barthel Index (MBI; <60 and ≥60). Among the SNPs of the IFG1 gene, five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron), rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3′ untranslated region; 3′UTR). Multiple logistic regression models were conducted to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After Bonferroni correction (pc), the A and G alleles of rs2162679 and rs6214 had significant differences between patients with IS and the controls [rs2162679, OR (95% CI) = 1.64 (1.17–2.31), p=0.004, pc=0.02; rs6214, OR (95% CI) = 1.52 (1.12–2.07), p=0.007, pc=0.035], respectively. However, the five selected SNPs were not related to the NIHSS and MBI scores. These results suggest that IGF1 may be associated with the development of IS. PMID:22969851

  18. Factors associated with unfavorable outcome in minor ischemic stroke

    PubMed Central

    Uehara, Toshiyuki; Ohara, Tomoyuki; Suzuki, Rieko; Toyoda, Kazunori; Minematsu, Kazuo

    2014-01-01

    Objectives: The purpose of this study was to elucidate the factors that correlate with unfavorable outcomes and to develop a simple validated model for assessing risk of unfavorable outcomes in patients with minor ischemic stroke. Methods: The derivation cohort included 1,313 patients hospitalized within 72 hours after onset with an initial NIH Stroke Scale score of 0 to 3 enrolled in a prospective, multicenter, observational study. Unfavorable outcome was defined as dependency (modified Rankin Scale score of 3–5) or death at 90 days. The predictive values of factors related to unfavorable outcome were evaluated. External validation was performed in 879 patients from a single-center stroke registry. Results: In the derivation cohort, a total of 203 patients (15%) had unfavorable outcomes. On multivariable analysis, women (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.30–2.94), age ≥72 years (OR 2.80, 95% CI 1.83–4.36), intra/extracranial vascular occlusive lesion (OR 2.80, 95% CI 1.82–4.28), leg weakness (OR 1.72, 95% CI 1.06–2.82), and extinction/inattention (OR 5.55, 95% CI 1.30–21.71) were independently associated with unfavorable outcome. Patients having both a vascular lesion and either leg weakness or extinction/inattention showed 4.63 (95% CI 2.23–9.33) times the risk of unfavorable outcome compared with those having neither. In the validation cohort, the risk was similar, at 3.77 (95% CI 1.64–8.37). Conclusions: Intra- and extracranial vascular imaging, NIH Stroke Scale items such as leg weakness and extinction/inattention, and their combination, as well as female sex and advanced age, may be useful for predicting unfavorable outcomes in patients with minor stroke. PMID:24907232

  19. Role of Mitochondria in Neonatal Hypoxic-Ischemic Brain Injury

    PubMed Central

    Lu, Yujiao; Tucker, Donovan; Dong, Yan; Zhao, Ningjun; Zhuo, Xiaoying; Zhang, Quanguang

    2016-01-01

    Hypoxic-ischemia (HI) causes severe brain injury in neonates. It’s one of the leading causes to neonatal death and pediatric disability, resulting in devastating consequences, emotionally and economically, to their families. A series of events happens in this process, e.g. excitatory transmitter release, extracelluar Ca2+ influxing, mitochondrial dysfunction, energy failure, and neuron death. There are two forms of neuron death after HI insult: necrosis and apoptosis, apoptosis being the more prevalent form. Mitochondria handle a series of oxidative reactions, and yield energy for various cellular activities including the maintainance of membrane potential and preservation of intracellular ionic homeostasis. Therefore mitochondria play a critical role in neonatal neurodegeneration following HI, and mitochondrial dysfunction is the key point in neurodegenerative evolution. Because of this, exploring effective mitochondria-based clinical strategies is crucial. Today the only efficacious clinic treatment is hypothermia. However, due to its complex management, clinical complication and autoimmune decrease, its clinical application is limited. So far, many mitochondria-based strategies have been reported neuroprotective in animal models, which offers promise on neonatal therapy. However, since their clinical effectiveness are still unclear, plenty of studies need to be continued in the future. According to recent reports, two novel strategies have been proposed: methylene blue (MB) and melatonin. Although they are still in primary stage, the underlying mechanisms indicate promising clinical applications. Every neurological therapeutic strategy has its intrinsic deficit and limited efficacy, therefore in the long run, the perfect clinical therapy for hypoxic-ischemic neonatal brain injury will be based on the combination of multiple strategies. PMID:27441209

  20. Carotid Artery Stenosis with Acute Ischemic Stroke: Stenting versus Angioplasty

    PubMed Central

    Villwock, Mark R.; Padalino, David J.; Deshaies, Eric M.

    2015-01-01

    Background When a patient with carotid artery stenosis presents emergently with acute ischemic stroke, the optimum treatment plan is not clearly defined. If intervention is warranted, and open surgery is prohibitive, endovascular revascularization may be performed. The use of stents places the patient at additional risk due to their thrombogenic potential. The intent of this study was to compare outcomes following endovascular approaches (angioplasty alone vs. stent) in the setting of acute stroke. Methods We extracted a population from the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2003–2011) composed of patients with carotid artery stenosis with infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with mechanical thrombectomy or thrombolysis were excluded. Categorical variables were compared between treatment groups with Chi-squared tests. Binary logistic regression was performed to evaluate mortality and iatrogenic stroke while controlling for age, case severity, and comorbidity burden. Results About 6,333 admissions met our criteria. A majority were treated via stenting (89%, n = 5,608). The angioplasty-alone group had significantly higher mortality (9.0% vs. 3.8%, p < 0.001) and iatrogenic stroke rate (3.9% vs. 1.9%, p < 0.001) than the stent group. The adjusted odds ratios of mortality and iatrogenic stroke for patients treated with angioplasty alone were 1.953 (p < 0.001) and 1.451 (p = 0.105), respectively, in comparison to patients treated with carotid stenting. Conclusion Multivariate analysis found the risk of mortality to be elevated following angioplasty alone. This may represent selection bias, but it also may indicate that symptomatic patients with stroke suffer from severe stenosis and unstable plaques that would benefit from stent placement. These results would caution angioplasty alone as an arm of a future randomized trial involving this severely burdened patient

  1. Carbonic Anhydrase Protects Fatty Liver Grafts against Ischemic Reperfusion Damage

    PubMed Central

    Bejaoui, Mohamed; Pantazi, Eirini; De Luca, Viviana; Panisello, Arnau; Folch-Puy, Emma; Hotter, Georgina; Capasso, Clemente; T. Supuran, Claudiu; Rosselló-Catafau, Joan

    2015-01-01

    Carbonic anhydrases (CAs) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. CAs are involved in numerous physiological and pathological processes, including acid-base homeostasis, electrolyte balance, oxygen delivery to tissues and nitric oxide generation. Given that these processes are found to be dysregulated during ischemia reperfusion injury (IRI), and taking into account the high vulnerability of steatotic livers to preservation injury, we hypothesized a new role for CA as a pharmacological agent able to protect against ischemic damage. Two different aspects of the role of CA II in fatty liver grafts preservation were evaluated: 1) the effect of its addition to Institut Georges Lopez (IGL-1) storage solution after cold ischemia; 2) and after 24h of cold storage followed by two hours of normothermic ex-vivo perfusion. In all cases, liver injury, CA II protein concentration, CA II mRNA levels and CA II activity were determined. In case of the ex-vivo perfusion, we further assessed liver function (bile production, bromosulfophthalein clearance) and Western blot analysis of phosphorylated adenosine monophosphate activated protein kinase (AMPK), mitogen activated protein kinases family (MAPKs) and endoplasmic reticulum stress (ERS) parameters (GRP78, PERK, IRE, eIF2α and ATF6). We found that CA II was downregulated after cold ischemia. The addition of bovine CA II to IGL-1 preservation solution efficiently protected steatotic liver against cold IRI. In the case of reperfusion, CA II protection was associated with better function, AMPK activation and the prevention of ERS and MAPKs activation. Interestingly, CA II supplementation was not associated with enhanced CO2 hydration. The results suggest that CA II modulation may be a promising target for fatty liver graft preservation. PMID:26225852

  2. Occupational noise and ischemic heart disease: A systematic review.

    PubMed

    Dzhambov, Angel M; Dimitrova, Donka D

    2016-01-01

    Noise exposure might be a risk factor for ischemic heart disease (IHD). Unlike residential exposure, however, evidence for occupational noise is limited. Given that high-quality quantitative synthesis of existing data is highly warranted for occupational safety and policy, we aimed at conducting a systematic review and meta-analysis of the risks of IHD morbidity and mortality because of occupational noise exposure. We carried out a systematic search in MEDLINE, EMBASE, and on the Internet since April 2, 2015, in English, Spanish, Russian, and Bulgarian. A quality-scoring checklist was developed a priori to assess different sources of methodological bias. A qualitative data synthesis was performed. Conservative assumptions were applied when appropriate. A meta-analysis was not feasible because of unresolvable methodological discrepancies between the studies. On the basis of five studies, there was some evidence to suggest higher risk of IHD among workers exposed to objectively assessed noise >75-80 dB for <20 years (supported by one high, one moderate, and one low quality study, opposed by one high and one moderate quality study). Three moderate and two low quality studies out of six found self-rated exposure to be associated with higher risk of IHD, and only one moderate quality study found no effect. Out of four studies, a higher mortality risk was suggested by one moderate quality study relying on self-rated exposure and one of high-quality study using objective exposure. Sensitivity analyses showed that at higher exposures and in some vulnerable subgroups, such as women, the adverse effects were considerably stronger. Despite methodological discrepancies and limitations of the included studies, occupational noise appeared to be a risk factor for IHD morbidity. Results suggested higher risk for IHD mortality only among vulnerable subgroups. Workers exposed to high occupational noise should be considered at higher overall risk of IHD. PMID:27569404

  3. Women and Ischemic Heart Disease: Recognition, Diagnosis and Management

    PubMed Central

    Park, Seong-Mi

    2016-01-01

    Cardiovascular disease is one of the most frequent causes of death in both males and females throughout the world. However, women exhibit a greater symptom burden, more functional disability, and a higher prevalence of nonobstructive coronary artery disease (CAD) compared to men when evaluated for signs and symptoms of myocardial ischemia. This paradoxical sex difference appears to be linked to a sex-specific pathophysiology of myocardial ischemia including coronary microvascular dysfunction, a component of the 'Yentl Syndrome'. Accordingly, the term ischemic heart disease (IHD) is more appropriate for a discussion specific to women rather than CAD or coronary heart disease. Following the National Heart, Lung, and Blood Institute Heart Truth/American Heart Association, Women's Ischemia Syndrome Evaluation and guideline campaigns, the cardiovascular mortality in women has been decreased, although significant gender gaps in clinical outcomes still exist. Women less likely undergo testing, yet guidelines indicate that symptomatic women at intermediate to high IHD risk should have further test (e.g. exercise treadmill test or stress imaging) for myocardial ischemia and prognosis. Further, women have suboptimal use of evidence-based guideline therapies compared with men with and without obstructive CAD. Anti-anginal and anti-atherosclerotic strategies are effective for symptom and ischemia management in women with evidence of ischemia and nonobstructive CAD, although more female-specific study is needed. IHD guidelines are not "cardiac catheterization" based but related to evidence of "myocardial ischemia and angina". A simplified approach to IHD management with ABCs (aspirin, angiotensin-converting enzyme inhibitors/angiotensin-renin blockers, beta blockers, cholesterol management and statin) should be used and can help to increases adherence to guidelines. PMID:27482251

  4. Can postmortem computed tomography detect antemortem hypoxic-ischemic encephalopathy?

    PubMed

    Shirota, Go; Ishida, Masanori; Shintani, Yukako; Abe, Hiroyuki; Ikemura, Masako; Fukayama, Masashi; Gonoi, Wataru

    2016-09-01

    The purpose of this study was to evaluate the usefulness of brain postmortem computed tomography (PMCT) findings for the detection of global hypoxia or hypoperfusion leading to hypoxic-ischemic encephalopathy (HIE) prior to death. Cadavers of individuals who died from non-traumatic causes were subjected to PMCT and pathological autopsy. Cases with an episode of cardiopulmonary arrest, hypoxia, or hypoperfusion that required intensive respiratory management at least 24 h before death and exhibited findings of HIE in conventional autopsy (HIE group, n = 6) were compared with those without such episodes prior to death (control group; overall, n = 37; age-matched, n = 8) with regard to four parameters: (1) width of the central sulcus (CS), (2) attenuation difference at the basal ganglia (BG) level, (3) attenuation difference between cerebral gray matter (GM) and cerebral white matter (WM), and (4) attenuation difference between cerebellar GM and cerebral GM. The results revealed significant differences in the width of the CS (P < 0.001), attenuation difference at the BG level (P < 0.001), and attenuation difference between cerebral GM and cerebral WM (P = 0.009) between the HIE group and the overall control group. When the age-matched control group and the HIE group were compared, there was a significant difference in the width of the CS (P = 0.026) and attenuation difference at the BG level (P < 0.001). Our results suggest that effacement of the sulcus of the cerebral hemisphere and the loss of contrast at the BG level on brain PMCT indicate the existence of HIE prior to death. PMID:27342771

  5. The Association Between Peptic Ulcer Disease and Ischemic Stroke

    PubMed Central

    Cheng, Tain-Junn; Guo, How-Ran; Chang, Chia-Yu; Weng, Shih-Feng; Li, Pi-I; Wang, Jhi-Joung; Wu, Wen-Shiann

    2016-01-01

    Abstract Stroke is a common cause of death worldwide, but about 30% of ischemic stroke (IS) patients have no identifiable contributing risk factors. Because peptic ulcer disease (PUD) and vascular events share some common risk factors, we conducted a population-based study to evaluate the association between PUD and IS. We followed up a representative sample of 1 million residents of Taiwan using the National Health Insurance Research Database from 1997 to 2011. We defined patients who received medications for PUD and had related diagnosis codes as the PUD group, and a reference group matched by age and sex was sampled from those who did not have PUD. We also collected data on medical history and monthly income. The events of IS occurred after enrollment were compared between the 2 groups. The data were analyzed using Cox proportional hazard models at the 2-tailed significant level of 0.05. The PUD group had higher income and prevalence of hypertension, diabetes mellitus (DM), heart disease, and hyperlipidemia. They also had a higher risk of developing IS with an adjusted hazard ratio of 1.31 (95% confidence interval: 1.20–1.41). Other independent risk factors included male sex, older age, lower income, and co-morbidity of hypertension, diabetes mellitus (DM), and heart disease. PUD is a risk factor for IS, independent of conventional risk factors such as male sex, older age, lower income, and co-morbidity of hypertension, DM, and heart disease. Prevention strategies taking into account PUD should be developed and evaluated. PMID:27258514

  6. Impact of cardiac magnetic resonance imaging in non-ischemic cardiomyopathies

    PubMed Central

    Kalisz, Kevin; Rajiah, Prabhakar

    2016-01-01

    Non-ischemic cardiomyopathies include a wide spectrum of disease states afflicting the heart, whether a primary process or secondary to a systemic condition. Cardiac magnetic resonance imaging (CMR) has established itself as an important imaging modality in the evaluation of non-ischemic cardiomyopathies. CMR is useful in the diagnosis of cardiomyopathy, quantification of ventricular function, establishing etiology, determining prognosis and risk stratification. Technical advances and extensive research over the last decade have resulted in the accumulation of a tremendous amount of data with regards to the utility of CMR in these cardiomyopathies. In this article, we review CMR findings of various non-ischemic cardiomyopathies and focus on current literature investigating the clinical impact of CMR on risk stratification, treatment, and prognosis. PMID:26981210

  7. [Dynamics of intracranial pressure in patients with massive ischemic stroke after decompressive craniotomy].

    PubMed

    Nikitin, A S; Burov, S A; Petrikov, S S; Asratian, S A; Gorshkov, K M; Krylov, V V

    2013-01-01

    The goal of the study was assessment of the value of ICP monitoring in patients with massive ischemic stroke after decompressive craniotomy. 12 patients with massive ischemic stroke were performed ICP monitoring after decompressive craniotomy. We identified 3 types of ICP dynamics: a) normal ICP, which no need to treat; b) ICP elevation to 20 mm Hg and more in postoperative period, which can be treated by nonsurgical therapy; c) refractory to therapy ICP elevation to 20 mm Hg and more with development of intracranial hypertension. We consider that ICP monitoring in patients with massive ischemic stroke after decompressive craniotomy can be useful for optimization of the therapy and correction of intracranial hypertension. PMID:24341041

  8. Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.

    PubMed

    Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco; Tassorelli, Cristina; Micieli, Giuseppe; Corasaniti, Maria Tiziana; Puccetti, Paolo; Fallarino, Francesca; Bagetta, Giacinto

    2016-01-01

    To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype. PMID:26518285

  9. Cost - effectiveness analysis of the antiplatelet treatment administered on ischemic stroke patients using goal programming approach

    NASA Astrophysics Data System (ADS)

    Rajendran, Rasvini; Zainuddin, Zaitul Marlizawati; Idris, Badrisyah

    2014-09-01

    There are numerous ways to prevent or treat ischemic stroke and each of these competing alternatives is associated with a different effectiveness and a cost. In circumstances where health funds are budgeted and thus fixed, cost-effectiveness analysis (CEA) can provide information on how to comprehend the largest health gains with that limited fund as CEA is used to compare different strategies for preventing or treating a single disease. The most common medications for ischemic stroke are the anti-platelet drugs. While some drugs are more effective than others, they are also more expensive. This paper will thus assess the CEA of anti-platelet drug available for ischemic stroke patients using goal programming (GP) approach subject to in-patients days and patients' quality-of-life. GP presents a way of striving towards several objectives simultaneously whereby in this case we will consider minimizing the cost and maximizing the effectiveness.

  10. Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

    PubMed

    Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori

    2014-10-01

    Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils. PMID:24792782

  11. Deep vein thrombosis after ischemic stroke: rationale for a therapeutic trial

    SciTech Connect

    Bornstein, N.M.; Norris, J.W.

    1988-11-01

    Deep venous thrombosis (DVT) in the legs occurs in 23% to 75% of patients with acute ischemic stroke, and pulmonary embolism accounts for about 5% of deaths. New heparinoid substances, lacking the hazards of more established anticoagulants, raise the question of DVT prophylaxis for these patients. Two hundred fifty consecutive acute ischemic stroke patients were evaluated for the presence of DVT of the legs in a feasibility study for a trial of low-molecular-weight heparin prophylaxis. Forty-nine patients were found suitable for the study, of whom 11 (22.5%) developed DVT. All patients underwent clinical examination, I-125 fibrinogen leg scanning, and impedance plethysmography. Five patients were sufficiently alert and without serious neurologic deficits to justify DVT prophylaxis. Recent advances in noninvasive diagnostic techniques to detect DVT early and the development of relatively safe heparinoid compounds increase the need for a prophylactic study in patients with ischemic stroke.

  12. Does nitric oxide generation contribute to the mechanism of remote ischemic preconditioning?

    PubMed

    Petrishchev, N N.; Vlasov, T D.; Sipovsky, V G.; Kurapeev, D I.; Galagudza, M M.

    2001-03-01

    The protective effect of local or remote ischemic preconditioning (IPC) on subsequent 40-min ischemic and 120-min reperfusion myocardial damage was investigated. Preconditioned rats underwent one cycle of myocardial ischemia/reperfusion consisting of 5-min ischemia produced as a left coronary artery (LCA) occlusion and 5 min of reperfusion. Remote IPC was produced as 15 min of small intestinal ischemia with 15 min of reperfusion as well as 30 min of limb ischemia with 15 min of reperfusion. A marked protective action was afforded by both IPC protocols with a more significant effect of local (classic) ischemic preconditioning. Since the protective effect of remote IPC was not abolished by nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine (L-NNA) it is concluded that NO generation may not be involved in the mechanism of remote IPC. PMID:11228397

  13. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  14. [Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke].

    PubMed

    Ershov, V I

    2011-01-01

    Comparative efficacy of neuroprotective preparations: actovegin, cerebrolysin and ceraxon was studied in 73 patients in the most acute phase of ischemic stroke. A control group included 33 patients in the most acute phase of ischemic stroke who received only basic treatment without neuroprotectors. Patient's state was assessed with the NIHSS, the original scale of E.I. Gusev and V.I. Skvortsova and the Barthel index. Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group. Barthel index scores did not differ in the groups studied. PMID:22224244

  15. Ischemic optic neuropathies and their models: disease comparisons, model strengths and weaknesses

    PubMed Central

    Miller, Neil R.

    2015-01-01

    Ischemic optic neuropathies (IONs) describe a group of diseases that specifically target the optic nerve and result in sudden vision loss. These include nonarteritic and arteritic anterior ischemic optic neuropathy (NAION and AAION) and posterior ischemic optic neuropathy (NPION, APION). Until recently, little was known of the mechanisms involved in ION damage, due to a lack of information about the mechanisms associated with these diseases. This review discusses the new models that closely mimic these diseases (rodent NAION, primate NAION, rodent PION). These models have enabled closer dissection of the mechanisms involved with the pathophysiology of these disorders and enable identification of relevant mechanisms and potential pathways for effective therapeutic intervention. Descriptions of the different models are included, and comparisons between the models, their relative similarities with the clinical disease, as well as differences are discussed. PMID:25690987

  16. Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

    PubMed

    Takeda, Seiichi; Toda, Takao; Nakamura, Kazuki

    2016-01-01

    We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. PMID:27381605

  17. Gait improvement after treadmill training in ischemic stroke survivors: A critical review of functional MRI studies☆

    PubMed Central

    Xiao, Xiang; Huang, Dongfeng; O’Young, Bryan

    2012-01-01

    Stroke survivors often present with abnormal gait, movement training can improve the walking performance post-stroke, and functional MRI can objectively evaluate the brain functions before and after movement training. This paper analyzes the functional MRI changes in patients with ischemic stroke after treadmill training with voluntary and passive ankle dorsiflexion. Functional MRI showed that there are some changes in some regions of patients with ischemic stroke including primary sensorimotor cortex, supplementary motor area and cingulate motor area after treadmill training. These findings suggest that treadmill training likely improves ischemic stroke patients’ lower limb functions and gait performance and promotes stroke recovery by changing patients’ brain plasticity; meanwhile, the novel treadmill training methods can better training effects. PMID:25337096

  18. Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke

    PubMed Central

    Hill, M D; Barber, P A; Demchuk, A M; Sevick, R J; Newcommon, N J; Green, T; Buchan, A M

    2000-01-01

    Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke. PMID:10862236

  19. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart.

    PubMed

    Evans, Cameron W; Iyer, K Swaminathan; Hool, Livia C

    2016-04-01

    Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent examples of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia. PMID:26980180

  20. [Changes in the hemoglobin A2 level of patients with ischemic heart disease].

    PubMed

    Damianova, L; Popnikolov, S; Pencheva, B; Angelova, A

    1989-01-01

    40 patients with ischemic heart disease were studied. In 60% of them a higher content of HbA2 was found. These data for higher frequency of HbA2 among the patients with ischemic heart disease do not correspond with the average incidence of the genetically determined anomaly A2-beta-thalassemia among the Bulgarian population. The negative data for increased methemoglobin, the shift of the oxygen dissociation curve to the right toward increased oxygen release from the hemoglobin molecule, the normalization of HbA2 after several days, the lack of anomalous fraction in the analyses lead to the conclusion that HbA2 plays a compensatory role in patients with ischemic heart disease and its dynamic changes could be used as a diagnostic test for ischemia. PMID:2474909

  1. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

    PubMed

    Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  2. Ischemic Colitis Is a Common Cause of Severe Hematochezia and Patient Outcomes Are Worse Than with Other Colonic Diagnoses

    PubMed Central

    Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O.G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.

    2013-01-01

    Background Outcomes of severe hematochezia from ischemic colitis vs. other colonic diagnoses have not been well studied. Objective Our purposes were: 1) to compare demographics and outcomes of patients hospitalized with severe hematochezia from ischemic colitis vs. other colonic diagnoses, 2) to compare inpatient vs. outpatient start of bleeding from ischemic colitis, 3) to describe potential risk factors. Design Prospective cohort study. Setting Tertiary referral academic centers. Patients Patients referred for gastroenterology consultation about severe hematochezia. Interventions Colonoscopic therapy was provided as indicated. Main outcome measurements Rebleeding, surgery and length of hospital stay Results Of 550 patients in the last 12 years with severe colonic hematochezia, 65 were caused by ischemia. Major 30 day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Patients with inpatient (vs. outpatient) ischemic colitis had significantly more and severe comorbidities at baseline and significantly higher rates of rebleeding, surgery & more hospital & intensive care unit days. Limitations Two-center study Conclusions Ischemic colitis was found more often in females and patients with anticoagulant usage, severe lung disease, higher creatinine, higher glucose, & more fresh frozen plasma transfused. Five patients with focal lesions had colonoscopic hemostasis. Major 30 day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Comparing outpatient vs. inpatient start of ischemic colitis, inpatients had significantly worse outcomes. PMID:21839438

  3. Rational modulation of the innate immune system for neuroprotection in ischemic stroke

    PubMed Central

    Amantea, Diana; Micieli, Giuseppe; Tassorelli, Cristina; Cuartero, María I.; Ballesteros, Iván; Certo, Michelangelo; Moro, María A.; Lizasoain, Ignacio; Bagetta, Giacinto

    2015-01-01

    The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction. PMID:25972779

  4. A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers.

    PubMed

    Perk, Sinem; Izamis, Maria-Louisa; Tolboom, Herman; Uygun, Basak; Berthiaume, Francois; Yarmush, Martin L; Uygun, Korkut

    2011-01-01

    With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine. PMID:22194843

  5. Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

    PubMed Central

    Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

    2016-01-01

    Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

  6. Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.

    PubMed

    Morrison, Helena; McKee, Dana; Ritter, Leslie

    2011-04-01

    As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain. PMID:21044968

  7. A Metabolic Index of Ischemic Injury for Perfusion-Recovery of Cadaveric Rat Livers

    PubMed Central

    Tolboom, Herman; Uygun, Basak; Berthiaume, Francois; Yarmush, Martin L.; Uygun, Korkut

    2011-01-01

    With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine. PMID:22194843

  8. Lack of associations between rs2910164 and rs11614913 polymorphisms and the risk of ischemic stroke

    PubMed Central

    Qin, Biyong; Zheng, Yan; Zhang, Wenjun; Wang, Chengmou; Wang, Jian; Cai, Zhiyou

    2015-01-01

    Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA genes may play a role in the development of cerebrovascular diseases including ischemic stroke through functionally modulating the expression of microRNA target genes. However, the current studies regarding the associations of the common microRNA polymorphisms with susceptibility to ischemic stroke have obtained discrepant results, which prompted us to perform a meta-analysis for a more precise estimation of the concerned associations. Relevant studies evaluating the associations between two common polymorphisms (miR-146a rs2910164 and miR-196a2 rs11614913) and the risk of ischemic stroke were retrieved from the PubMed, Embase, Cochrane Library, Google Scholar, Chinese Wanfang, Chinese Biomedical Database, and Chinese National Knowledge Infrastructure databases. The odds ratio (OR) with its 95% confidence interval (95% CI) were pooled to assess the strength of the associations using RevMan 5.2 and Stata 12.0 software. A total of 5 case-control studies with 2069 cases and 2061 controls on rs2910164, 4 case-control studies with 1873 cases and 1856 controls on rs11614913 polymorphisms were enrolled in the meta-analysis. Overall, neither allele frequency nor genotype distribution of the two common polymorphisms was found to be associated with risk for ischemic stroke in all genetic models. The subgroup analysis revealed a significant association between miR-146a rs2910164 polymorphism and increased risk of ischemic stroke in large sample size group and in Koreans under homozygous, allele, dominant and recessive models. The present meta-analysis suggests that the two common polymorphisms (rs2910164, rs11614913) may not contribute to the susceptibility to ischemic stroke. However, more well-designed studies with large sample size are warranted to further validate the results in different ethnicities. PMID:26770439

  9. A Population-Based Study of 30-day Incidence of Ischemic Stroke Following Surgical Neck Dissection

    PubMed Central

    MacNeil, S. Danielle; Liu, Kuan; Garg, Amit X.; Tam, Samantha; Palma, David; Thind, Amardeep; Winquist, Eric; Yoo, John; Nichols, Anthony; Fung, Kevin; Hall, Stephen; Shariff, Salimah Z.

    2015-01-01

    Abstract The objective of this study was to determine the 30-day incidence of ischemic stroke following neck dissection compared to matched patients undergoing non-head and neck surgeries. A surgical dissection of the neck is a common procedure performed for many types of cancer. Whether such dissections increase the risk of ischemic stroke is uncertain. A retrospective cohort study using data from linked administrative and registry databases (1995–2012) in the province of Ontario, Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery, and comorbidities to patients undergoing non-head and neck surgeries. The primary outcome was ischemic stroke assessed in hospitalized patients using validated database codes. A total of 14,837 patients underwent surgical neck dissection. The 30-day incidence of ischemic stroke following the dissection was 0.7%. This incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006; 0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic stroke in patients undergoing neck dissection is similar to matched patients undergoing thoracic surgery (0.5%, P = 0.26) and colectomy (0.5%, P = 0.1). Factors independently associated with a higher risk of stroke in 30 days following neck dissection surgery were of age ≥75 years (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05–2.53), and a history of diabetes (OR 1.60, 95% CI 1.02–2.49), hypertension (OR 2.64, 95% CI 1.64–4.25), or prior stroke (OR 4.06, 95% CI 2.29–7.18). Less than 1% of patients undergoing surgical neck dissection will experience an ischemic stroke in the following 30 days. This incidence of stroke is similar to thoracic surgery and colectomy. PMID:26287406

  10. Preventive Effects of Antioxidants and Exercise on Muscle Atrophy Induced by Ischemic Reperfusion

    PubMed Central

    Umei, Namiko; Ono, Takeya; Oki, Sadaaki; Otsuka, Akira; Otao, Hiroshi; Tsumiyama, Wakako; Tasaka, Atsushi; Ishikura, Hideki; Aihara, Kazuki; Sato, Yuta; Shimizu, Michele Eisemann

    2014-01-01

    [Purpose] This study aimed to determine whether muscle atrophy induced by ischemic reperfusion injury in rats can be prevented by the administration of antioxidants and exercise. [Subjects] Rats were randomly divided into five groups: non-treated, ischemic, exercise, ascorbic acid and exercise, and tocopherol and exercise. [Methods] The relative weight ratio of the soleus muscle and the length of the soleus muscle fiber cross-section minor axis were used for the evaluation of muscle atrophy. Pain was assessed as the weight-bearing ratio of the ischemic side. A multiple comparison test and the paired t-test were used for the statistical analyses. [Results] Compared with the non-treated group, the relative weight ratios of the soleus muscle and the lengths of the soleus muscle fiber cross-section minor axis significantly decreased in the other groups. Excluding the non-treated group, the relative weight ratios of the soleus muscle were heaviest in the tocopherol and exercise group. Excluding the non-treated group, the lengths of the soleus muscle fiber cross-section minor axis were longest in the tocopherol and exercise group, followed by the ischemic, exercise, and ascorbic acid and exercise groups. The amount of antioxidant substances did not decrease on the weight-bearing ratio of the ischemic side. [Conclusion] In this study, using an experimental rat model, we confirmed that antioxidants and exercise effect muscle atrophy induced by ischemic reperfusion. The results show that muscle regeneration was facilitated by phagocytosis in the tocopherol and exercise group. PMID:25540491

  11. Adjuvant Chinese Herbal Products for Preventing Ischemic Stroke in Patients with Atrial Fibrillation

    PubMed Central

    Muo, Chih-Hsin; Chiu, Hsienhsueh Elley; Liu, Chun-Ting

    2016-01-01

    Objective Chinese herbal products (CHPs) are widely used for atrial fibrillation (AF) in Taiwan. We investigated the effect of adjuvant CHPs in preventing ischemic stroke in patients with AF. Methods Taiwanese patients in the Health Insurance Database newly diagnosed with AF during 2000–2011 were enrolled. Medication treatment with/without CHPs was administered within 7 days after the AF diagnosis. The clinical endpoint was an ischemic stroke. The Chi-square test, Fisher’s exact test, and Student t test were used to examine differences between the traditional Chinese medicine (TCM) and non-TCM cohorts. Cox proportional hazard regression was used to assess the risk for ischemic stroke between two cohorts. Results Three hundred and eleven patients underwent TCM treatment and 1715 patients did not. Compared to non-TCM users, TCM users had a lower incidence of stroke (12.59% vs. 1.93%, respectively) and lower risk of stroke [CHA2DS2-VASc score = 0–2 (hazard ratio = 0.20; 95% confidence interval = 0.06–0.65)]. Compared to non-TCM users, the stroke risk was significantly lower in TCM users with AF who were female or younger than 65 years, but not in males, people more than 65 years old, or people with comorbidities. Compared to TCM users, non-TCM users who received conventional treatment had a higher