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Sample records for acute cerebral ischemia

  1. Purine Metabolism in Acute Cerebral Ischemia

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    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  2. Early CT findings in acute middle cerebral artery ischemia

    International Nuclear Information System (INIS)

    Mohamed, M.; Poniatowska, R.; Boguslawska, R.; Krawczyk, R.; Rejnowski, J.; Ryterski, J.; Tarrakowski, J.; Mendel, T.

    2004-01-01

    Stroke is characterized by a sudden onset of focal central neurological deficit, with symptoms lasting more than 24 hours, that can be fatal. The introduction of anti-coagulation treatments, together with continuous advances inneuroimaging techniques, have a positive impact, both on morbidity and mortality in stroke patients. It must be stressed, that 'therapeutic window' for fibrolytic treatment is up to 3 hours. The group consisted of 50 patients with clinical diagnosis of stroke, who met the following criteria: first ever, non-hemorrhagic stroke, middle cerebral artery territory involvement, first CT performed within 12 hours from the onset of symptoms, control CT, performed within 7 days, confirming signs of infarction in the distribution of middle cerebral artery. All CT were performed without contrast administration. First CT examinations were retrospectively studied for early evidence of ischemic changes, subsequently depicted as infarction in the control CT. Hyperdencemiddle cerebral artery sign (HMCAS), hypoattenuation of lentiform nucleus (ALN), loss of insular ribbon (LIR), hemispheric sulcus effacement (HES) were found as early abnormalities CT examinations continue to play a dominant role in the initial diagnosis of acute cerebral ischemia. Signs of early ischemia can be often detected within the first three hours from the onset, in the hyper acute phase. CT is used in evaluation of recent symptoms in acute phase and proper selection of patients for thrombolysis with significant therapeutic results. [author

  3. Magnetic resonance spectroscopy and imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    Rijen, P.C. van.

    1991-01-01

    In-vivo proton and phosphorus magnetic resonance spectroscopy was used to detect changes in cerebral metabolism during ischemia and other types of metabolic stress. Magnetic resonance imaging was performed in an animal model to observe morphological alterations during focal cerebral ischemia. Spectroscopy was performed in animal models with global ischemia, in volunteers during hyperventilation and pharmaco-logically altered cerebral perfusion, and in patients with acute and prolonged focal cerebral ischemia. (author). 396 refs.; 44 figs.; 14 tabs

  4. Magnetic resonance imaging in acute stage of cerebral ischemia

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    Yamagata, Sen; Kikuchi, Haruhiko; Ihara, Ikuo

    1986-01-01

    The value of the nuclear magnetic resonance image (MRI) was investigated in the acute stage of experimental cerebral ischemia. The MRI system employed was designed for clinical use, and the superconducting magnet was operated at a field strength of 1.5 tesla. Ischemic insult was made by transorbital occlusion of the middle cerebral artery (MCA) permanently in 4 cats and temporarily in 2 cats. After MCA occlusion the regional cerebral blood flow (rCBF) was measured on the affected cortex, and 5 cats with rCBF below 10 ml/100 g/min and one with rCBF over 15 ml/100 g/min were studied. In the permanent occlusion group, MRI was performed every 2 hours from 4 to 12 hours after MCA occlusion and another MRI was carried out 20 min after gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) intravenous administration. The earliest changes were found 6 to 8 hours after MCA occlusion on the spin echo image (repetition time = 1.4 sec, echo time = 70 msec) in 3 cats with severe ischemia. It was postulated that the ischemic lesion could be depicted less than 6 hours on more T 2 -weighted images. The increased intensity area was markedly enhanced with Gd-DTPA 12 hours after occlusion. In the recirculation group, the increased intensity area was observed on enhanced MRI in a cat with recirculation as early as one hour after MCA occlusion, although it was not found on the plain MRI. In the other cat with recirculation after 2 hours' occlusion, definite lesion was found in all parameter images without enhancement. The results suggest that changes in cerebral ischemia can be obtained on the MRI earlier than X-ray computed tomography, and that it may be possible to determine the severity of the ischemic brain injury by the MRI findings. (author)

  5. Pharmacologicalmodification of thegabaergicsystem as a potentialvariant of cerebral protection in acute cerebral ischemia

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    Олександр Володимирович Тихоновський

    2015-10-01

    Full Text Available The aim is to study the possible impact of some derivatives of gamma-aminobutyric acid (GABA, piracetam, picamilon and Krebs cycle intermediates - succinate (as sodium salt on the pathobiochemical changes in the central nervous system, that occur under experimental playing of acute ischemic tissue damage of the cerebrum.Research methods: The study was conducted in 96 rats Wistar, who were on a standardized vivarium diet. Cerebral ischemia was caused by bond of the unilateral common carotid artery. All drugs were administered intraperitoneally once daily for 4 days after modeling of an acute cerebral ischemia after which animals were withdrawn from experiment. In the brain tissues concentrations of pyruvic, izocitric, dairy and apple acids were determined. The activity of antioxidant enzymes: catalase and superoxide dysmutaza. In addition, the brain tissues the contents of lipid peroxidation products were evaluated – diene conjugates and malonic dialdehyde. Level of brain energy production was judged by the content of the adenylic nucleotide and also phosphocreatine . The degree of destruction of the brain cells was assessed by activity of the enzyme lactate dehydrogenase in the blood and brain fraction of the creatine phosphokinase.Research results: As a result of studies, on the 4th day of ischemia a significant carbohydrate metabolism is detected, which is reflected in the sharp strengthening of anaerobic glycolysis and reduced activity of the Krebs cycle reactions, as evidenced by a significant increase in quantity of lactate and decrease in quantity of malate, isocitrate and pyruvate.A sharp strengthening of anaerobic glycolysis results in the accumulation of oxidized products and intermediates especially the latter product – lactic acid. Metabolic acidosis develops against the background of energy failure, which leads to activation of lipid peroxidation reactions. Courses appointment of the cyclic derivatives of GABA piracetam

  6. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

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    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-01-01

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

  7. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

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    Hua, Fang, E-mail: fhua2@emory.edu [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States); Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G. [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States)

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  8. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

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    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  9. Gene expression in cerebral ischemia: a new approach for neuroprotection.

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    Millán, Mónica; Arenillas, Juan

    2006-01-01

    Cerebral ischemia is one of the strongest stimuli for gene induction in the brain. Hundreds of genes have been found to be induced by brain ischemia. Many genes are involved in neurodestructive functions such as excitotoxicity, inflammatory response and neuronal apoptosis. However, cerebral ischemia is also a powerful reformatting and reprogramming stimulus for the brain through neuroprotective gene expression. Several genes may participate in both cellular responses. Thus, isolation of candidate genes for neuroprotection strategies and interpretation of expression changes have been proven difficult. Nevertheless, many studies are being carried out to improve the knowledge of the gene activation and protein expression following ischemic stroke, as well as in the development of new therapies that modify biochemical, molecular and genetic changes underlying cerebral ischemia. Owing to the complexity of the process involving numerous critical genes expressed differentially in time, space and concentration, ongoing therapeutic efforts should be based on multiple interventions at different levels. By modification of the acute gene expression induced by ischemia or the apoptotic gene program, gene therapy is a promising treatment but is still in a very experimental phase. Some hurdles will have to be overcome before these therapies can be introduced into human clinical stroke trials. Copyright 2006 S. Karger AG, Basel.

  10. Diagnostic radiology of apoplexy - imaging of cerebral ischemia

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    Rieber, A.; Tomczak, R.; Brambs, H.J.

    1998-01-01

    The recent enhancements achieved in CT and MR imaging techniques have launched a debate about the techniques preferrably to be applied for diagnostic evaluation of acute cerebral stroke. At present, CT still is the modality of choice for primary evaluation of cerebral ischemia, due to relative cost-effectiveness, high availability, and the capability to reliably differentiate ischemia from hemorrhage. MRI on the other hand is superior to CT in detecting and imaging the infarction area within the first few hours, especially if the technique of diffusion-weighted sequencing is applied. Current research focuses on determining whether MRI with perfusion and diffusion-weighted sequencing will yield images distinctly showing the penumbra on the one hand, and the damaged brain tissue on the other. It remains to be seen whether improved tomographic imaging will lead to novel approaches for therapy. (orig./CB) [de

  11. Discussion on the treatment of cerebral ischemia-reperfusion injuries following intra-arterial thrombolysis

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    Tian Hong; Song Chuan; Fan Ruxiong; Zhou Huchuan; Zhang Yubo; Zang Qiaoli; Zhang Yunquan; Liu Lei

    2011-01-01

    Objective: To investigate the therapeutic method of cerebral ischemia-reperfusion injuries occurred after arterial thrombolytic therapy for acute cerebral infarction. Methods: Thirty-five patients, encountered in authors' Department since Oct. 2005, with cerebral ischemia-reperfusion injuries, which occurred after thrombolytic therapy by using arterial perfusion of urokinase for acute cerebral infarction, were enrolled in this study. The clinical data were retrospectively analyzed. Results: After the thrombolytic therapy, completer or partial recanalization of the occluded cerebral arteries was obtained in 33 cases, while secondary cerebral hemorrhage occurred in 13 cases, of whom cerebral parenchyma bleeding was seen in 2 and hemorrhagic infarction in 11. Different degrees of cerebral edema were found in all 33 cases. Among them significant shift of the midline structures was detected in 18 (54.5%), which was manifested clinically as the worsening of disturbance of consciousness. Strict control of blood pressure, prompt adjustment of dehydration medication, strengthening the cerebral protection measures, cerebral decompression by fenestration, etc. were carried out. All the patients took a turn for the better and were out of danger with remarkable improvement of neurological functions except one patient who died from massive intracerebral hemorrhage. Conclusion: Usually, different degrees of reperfusion injuries will develop after thrombolytic therapy for cerebral arterial infarction. Strictly controlling blood pressure, promptly adjusting dehydration medication and strengthening cerebral protection are the keys to reduce the severity of cerebral reperfusion injuries. (authors)

  12. MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

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    Jian-Min Piao

    2018-04-01

    Full Text Available Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381 on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB by targeting leucine-rich repeat C4 protein (LRRC4 through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. Methods: Rat models of CLB and middle cerebral artery occlusion (MCAO were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA to determine contents of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, interleukin-10 (IL-10, nerve growth factor (NGF and neurite outgrowth inhibitor -A (Nogo-A, Reverse transcription quantitative polymerase chain reaction (RT-qPCR and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF. Results: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group, while BrdU-positive cell number, contents of NGF and

  13. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  14. Local fibrinolytic therapy for patients with cerebral embolism and reversibility of cerebral ischemia in ultra-acute stage

    International Nuclear Information System (INIS)

    Koizumi, Takayuki

    1993-01-01

    The present study was undertaken to determine candidates for fibrinolytic therapy in cerebral embolism. Forty-three patients were examined by single photon emission computed tomography (SPECT) using 99m c-d, hexamethyl-propylene-amine oxime (HM-PAO) or N-isopropyl p[ 123 I]-iodoamphetamine ( 123 I-IMP) just before and after intra-arterial local fibrinolytic therapy. Regional cerebellar ratio (R/Ce) and asymmetry index (AI) were calculated just before the treatment (n=9). Quantitative analysis was performed after the treatment (n=all). SPECT images taken within 24 hours after the treatment fell into three patters: normal perfusion, hypoperfusion, and hyperperfusion. Patients showing normal perfusion pattern after complete recanalization developed no or smaller infarction on CT scans. However, patients showing either hypoperfusion or hyperperfusion developed large infarction. Regions with R/Ce ratio of 0.3 or smaller and/or AI of 1.5 or greater were irreversible, which was associated with cerebral infarction regardless of the duration of ischemia. On the other hand, regions with R/Ce of 0.5 or greater or AI of 1.2 or smaller were reversible with no association of infarction. Intra-arterial local fibrinolytic therapy seems to be helpful for patients with slight reduction of regional cerebral blood flow (i.e., R/Ce>0.5, AI 1.5). These findings indicate that SPECT is capable of determining reversibility of ischemic region, thereby contributing to better management of patients with acute cerebral embolism. (N.K.)

  15. β2-Adrenergic Receptor-Mediated HIF-1α Upregulation Mediates Blood Brain Barrier Damage in Acute Cerebral Ischemia

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    Yanyun Sun

    2017-08-01

    Full Text Available Disruption of the blood brain barrier (BBB within the thrombolytic time window is an antecedent event to intracerebral hemorrhage in ischemic stroke. Our recent studies showed that 2-h cerebral ischemia induced BBB damage in non-infarcted area and secreted matrix metalloproteinase-2 (MMP-2 accounted for this disruption. However, the factors that affect MMP-2 secretion and regulate BBB damage remains unknown. Since hypoxia-inducible factor-1 alpha (HIF-1α was discovered as a mater regulator in hypoxia, we sought to investigate the roles of HIF-1α in BBB damage as well as the factors regulating HIF-1α expression in the ischemic brain. in vivo rat middle cerebral artery occlusion (MCAO and in vitro oxygen glucose deprivation (OGD models were used to mimic ischemia. Pretreatment with HIF-1α inhibitor YC-1 significantly inhibited 2-h MCAO-induced BBB damage, which was accompanied by suppressed occludin degradation and vascular endothelial growth factor (VEGF mRNA upregulation. Interestingly, β2-adrenergic receptor (β2-AR antagonist ICI 118551 attenuated ischemia-induced BBB damage by regulating HIF-1α expression. Double immunostaining showed that HIF-1α was upregulated in ischemic neurons but not in astrocytes andendothelial cells. Of note, HIF-1α inhibition with inhibitor YC-1 or siRNA significantly prevented OGD-induced VEGF upregulation as well as the secretion of VEGF and MMP-2 in neurons. More importantly, blocking β2-AR with ICI 118551 suppressedHIF-1α upregulation in ischemic neurons and attenuated occludin degradation induced by the conditioned media of OGD-treatedneurons. Taken together, blockade of β2-AR-mediated HIF-1α upregulation mediates BBB damage during acute cerebral ischemia. These findings provide new mechanistic understanding of early BBB damage in ischemic stroke and may help reduce thrombolysis-related hemorrhagic complications.

  16. Relaxation along a fictitious field (RAFF and Z-spectroscopy using alternating-phase irradiation (ZAPI in permanent focal cerebral ischemia in rat.

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    Kimmo T Jokivarsi

    Full Text Available Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI, were quantified together with conventional relaxation parameters (T1, T2 and T1ρ and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1 Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2 RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3 MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4 ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

  17. Ligustrazine monomer against cerebral ischemia-reperfusion injury

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    Hai-jun Gao

    2015-01-01

    Full Text Available Ligustrazine (2,3,5,6-tetramethylpyrazine is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyloxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine.

  18. Animal models of cerebral ischemia

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    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  19. Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

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    Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

    2017-09-01

    A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

  20. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

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    Wang-shu Xu

    2016-01-01

    Full Text Available Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  1. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice

    International Nuclear Information System (INIS)

    Cao Canxiang; Yang Qingwu; Lv Fenglin; Cui Jie; Fu Huabin; Wang Jingzhou

    2007-01-01

    Inflammatory reaction plays an important role in cerebral ischemia-reperfusion injury, however, its mechanism is still unclear. Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water content, cerebral infarct size and neurologic impairment in C3H/Hej mice were obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and electron microscopic results showed that cerebral ischemia-reperfusion injury in C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-α and IL-6 contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with ELISA. The results showed that TLR4 participates in the process of cerebral ischemia-reperfusion injury probably through decrease of inflammatory cytokines. TLR4 may become a new target for prevention of cerebral ischemia-reperfusion injury. Our study suggests that TLR4 is one of the mechanisms of cerebral ischemia-reperfusion injury besides its important role in innate immunity

  2. Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia.

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    Chen, Zheng-Zhen; Yang, Dan-Dan; Zhao, Zhan; Yan, Hui; Ji, Juan; Sun, Xiu-Lan

    2016-04-01

    Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size. The amount of astrocytes and the somal volume of the microglia cell body were analyzed by immunohistochemistry and stereological estimates. Western blotting was used to determine the protein expressions. Memantine prevented cerebral ischemia-induced brain infarct and neuronal injury, and reduced oxygen-glucose deprivation-induced cortical neuronal apoptosis. Moreover, memantine reduced the amount of the damaged astrocytes and over activated microglia after 24h of ischemia. In the early phase of ischemia, higher production of MMP-9 was observed, and thereby collagen IV was dramatically disrupted. Meanwhile, the post-synaptic density protein 95(PSD-95) was also severely cleavaged. Memantine decreased MMP-9 secretion, prevented the degradation of collagen IV in mouse brain. PSD-95 cleavage was also inhibited by memantine. These results suggested that memantine exerted neuroprotection effects in acute ischemic brain damage, partially via improving the functions of neurovascular unit. Taking all these findings together, we consider that memantine might be a promising protective agent against ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dynamics of cognitive disturbances in rats with acute cerebral ischemia on the background of introduction of 0.9 % solution NaCl

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    Андрій Ігорович Семененко

    2015-06-01

    Full Text Available For today there are no clear recommendations on infusion therapy at the disease and injuries of brain, and infusion preparations are commonly used empirically. Within the framework of the complex study of an influence of the different infusion remedies on brain at an experimental ischemia of brain, an aim of this work is to investigate how the 0,9 % solution of NaCl influences on the dynamics of cognitive functions and neurological status of the rats with an acute cerebral ischemia at the course medical introduction into an animal organism.Methods. Experiments were carried out on 60 white rats-males. An acute disturbance of cerebral blood circulation (ADCBC was modeled by means of the two-sided dressing of internal carotid arteries. The 0,9 % solution of NаСІ was injected intravenously in catheterized thigh vein 2,5 ml/kg 2 times/day (5 ml/kg for a day. The first introduction was carried out in 30 minutes after ADCBC and then every day in 12 hours during 7 days. The control groups consist of intact rats that received 0,9 % NаСІ and animals with a model ischemia without treatment.Neurological deficiency in animals was defined on the scale stroke-index McGrow C. P. The dynamics of position-finding activity was assessed in experiment “an open field”. An assessment of animal capacity to training and memorization of an aversive stimulus was studied in the test of conditioned response of passive avoidance. The results were processed using the program StatPlus 2009.Results. The study showed that bilateral carotid occlusion in rats without treatment is followed not only by the high animal lethality but also by the development of a hard neurological symptomatology and then by essential disturbance of mnestic functions in animals that survived during the recovery period of model insult (р<0,01.The study of lethality dynamics, neurological status, behavioral responses in rats with ADCBC on the model of bilateral carotid occlusion showed that the

  4. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Nabi Shamsaei; Mehdi Khaksari; Sohaila Erfani; Hamid Rajabi; Nahid Aboutaleb

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral isch-emic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction th rough occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic ex-ercise signiifcantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  5. Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection

    OpenAIRE

    Yu, Yong-Qiang; Liu, Lian-Cheng; Wang, Fa-Cai; Liang, Yan; Cha, Da-Qin; Zhang, Jing-Jing; Shen, Yu-Jun; Wang, Hai-Ping; Fang, Shengyun; Shen, Yu-Xian

    2009-01-01

    Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion w...

  6. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Ozbilgin, Sule; Yılmaz, Osman; Ergur, Bekir Ugur; Hancı, Volkan; Ozbal, Seda; Yurtlu, Serhan; Gunenc, Sakize Ferim; Kuvaki, Bahar; Kucuk, Burcu Ataseven; Sisman, Ali Rıza

    2016-06-01

    Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. Copyright © 2016. Published by Elsevier Taiwan.

  7. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Sule Ozbilgin

    2016-06-01

    Full Text Available Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats.

  8. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

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    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  9. Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

    Science.gov (United States)

    Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

    2017-12-01

    Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

  10. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

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    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  11. Identification of proteins regulated by curcumin in cerebral ischemia.

    Science.gov (United States)

    Shah, Fawad-Ali; Gim, Sang-Ah; Sung, Jin-Hee; Jeon, Seong-Jun; Kim, Myeong-Ok; Koh, Phil-Ok

    2016-03-01

    Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

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    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  13. Diffusion-weighted MRI in acute cerebral stroke

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, Hideichi; Kobayashi, Masahito; Suga, Sadao; Kawase, Takeshi; Nagasawa, Masakazu; Sadanaga, Humiko; Okamura, Miyuki; Kanai, Yoshihiro; Mihara, Ban [Mihara Memorial Hospital, Isezaki, Gunma (Japan)

    1999-03-01

    Diffusion-weighted MRI has been demonstrated to be valuable in the assessment of cerebral stroke. Recent advance in MR systems of hardware with larger maximum gradient amplitude and faster imaging strategies, such as EPI, has made it possible to acquire whole brain diffusion-weighted imaging (DWI) in less that one minute. The purposes of this study are to evaluate clinical usefulness of DWI and to clarify pitfalls in the diagnosis of acute cerebral stroke. Seventeen patients with 18 ischemic lesions were studied. DWI were taken with 1.5 Tesla MRI (Magnetom Vision, Siemens, Germany) using EPI sequence. Fifteen lesions out of them (3 in cerebral cortex, 9 in basal ganglia/deep white matter and 3 in cerebellum) were studied serially at various times up to 147 days. Acute cerebral infarction was seen clearly as an area of hyperintensity with DWI and as hypointensity in apparent diffusion coefficient (ADC) maps which are indicative of decreased diffusion. DWI detected areas of hyperintense acute infarcts, as early as 2.5 hours after onset, which were not visualized on T{sub 2}-weighted image (T2WI). The lesion of cerebral infarction became isointense in ADC maps at 14-28 days after onset, whereas with DWI it became isointense at about 2 months. Because ADC changed earlier than DWI, ADC maps were useful for differentiate acute from nonacute lesion in cases of recurrent stroke within a short period. In a patient with transient global amnesia for 7 hours, DWI did not show any lesion at 8 hours. In terms of cerebral hemorrhage, lesions were seen as area of hyperintensity in DWI at 3 days and were not distinguishable from that of infarct. Despite limitations in the diagnosis of transient ischemia and cerebral hemorrhage, DWI is a useful technique for early detection of cerebral infarction, especially within the first 6 hours after stroke onset. (author)

  14. Diffusion-weighted MRI in acute cerebral stroke

    International Nuclear Information System (INIS)

    Takayama, Hideichi; Kobayashi, Masahito; Suga, Sadao; Kawase, Takeshi; Nagasawa, Masakazu; Sadanaga, Humiko; Okamura, Miyuki; Kanai, Yoshihiro; Mihara, Ban

    1999-01-01

    Diffusion-weighted MRI has been demonstrated to be valuable in the assessment of cerebral stroke. Recent advance in MR systems of hardware with larger maximum gradient amplitude and faster imaging strategies, such as EPI, has made it possible to acquire whole brain diffusion-weighted imaging (DWI) in less that one minute. The purposes of this study are to evaluate clinical usefulness of DWI and to clarify pitfalls in the diagnosis of acute cerebral stroke. Seventeen patients with 18 ischemic lesions were studied. DWI were taken with 1.5 Tesla MRI (Magnetom Vision, Siemens, Germany) using EPI sequence. Fifteen lesions out of them (3 in cerebral cortex, 9 in basal ganglia/deep white matter and 3 in cerebellum) were studied serially at various times up to 147 days. Acute cerebral infarction was seen clearly as an area of hyperintensity with DWI and as hypointensity in apparent diffusion coefficient (ADC) maps which are indicative of decreased diffusion. DWI detected areas of hyperintense acute infarcts, as early as 2.5 hours after onset, which were not visualized on T 2 -weighted image (T2WI). The lesion of cerebral infarction became isointense in ADC maps at 14-28 days after onset, whereas with DWI it became isointense at about 2 months. Because ADC changed earlier than DWI, ADC maps were useful for differentiate acute from nonacute lesion in cases of recurrent stroke within a short period. In a patient with transient global amnesia for 7 hours, DWI did not show any lesion at 8 hours. In terms of cerebral hemorrhage, lesions were seen as area of hyperintensity in DWI at 3 days and were not distinguishable from that of infarct. Despite limitations in the diagnosis of transient ischemia and cerebral hemorrhage, DWI is a useful technique for early detection of cerebral infarction, especially within the first 6 hours after stroke onset. (author)

  15. Post-Traumatic Late Onset Cerebral Ischemia

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    Gencer Genc

    2014-03-01

    Full Text Available Artery-to-artery emboli or occlusion of craniocervical arteries mostly due to dissection are the most common causes of ischemia after trauma. A 29 year-old male had been admitted to another hospital with loss of consciousness lasting for about 45 minutes after a hard parachute landing without head trauma three days ago. As his neurological examination and brain CT were normal, he had been discharged after 24 hours of observation. Two days after his discharge, he was admitted to our department with epileptic seizure. His neurological examination revealed left hemianopia. After observing occipital subacute ischemia at right side in brain magnetic resonance imaging (MRI, we performed cerebral angiography and no dissection was observed. Excluding the rheumatologic, cardiologic and vascular events, our final diagnosis was late onset cerebral ischemia. Anti-edema and antiepileptic treatment was initiated. He was discharged with left hemianopia and mild cognitive deficit. We suggest that it will be wise to hospitalize patients for at least 72 hours who has a history of unconsciousness following trauma.

  16. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  17. Effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia

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    Xiang-Long Hong

    2016-07-01

    Full Text Available Objective: To explore the effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia, and the role of autophagy in the cerebral ischemia injury. Methods: The healthy male SD rats were randomized into the sham operation group, the ischemia model group, baicalin treatment group (100 mg/kg, and 3MA group (15 mg/kg, with 10 rats in each group. Transient focal cerebral ischemia injury model in rats was induced by occlusion of middle cerebral artery (MCA for 180 min. The rats were given the corresponding drugs through the tail veins 30 min before molding. Half of the specimens were used for TTC staining to analyze the cerebral infarction volume. The others were used to determine the expression of Beclin-1 in the brain tissues by Western-blot. Results: When compared with the ischemia model group, the cerebral infarction volume in 3MA group was significantly increased, while that in baicalin treatment group was significantly reduced, and the comparison among the groups was statistically significant. When compared with the ischemia model group, Beclin-1 expression level in baicalin treatment group was significantly elevated, while Beclin-1 expression level in 3MA group was significantly higher than that in the sham-operation group but lower than that in the ischemia model group. Conclusions: The autophagy level of brain tissues in normal rats is low. The cerebral ischemia can activate autophagy. The activated autophagy is probably involved in the neuroprotection of cerebral ischemia injury. Application of 3MA to inhibit the occurrence of autophagy can aggravate the cerebral injury. Baicalin can significantly improve the cerebral ischemia injury and promote the occurrence of autophagy, whose mechanism is probably associated with the up-regulation of Beclin-1 expression to promote the activation of type III PI3K signal transduction pathway.

  18. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  19. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    International Nuclear Information System (INIS)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  20. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

    Science.gov (United States)

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-06-10

    The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

  1. Sequential assessment of regional cerebral blood flow, regional cerebral blood volume, and blood-brain barrier in focal cerebral ischemia: a case report

    International Nuclear Information System (INIS)

    Di Piero, V.; Perani, D.; Savi, A.; Gerundini, P.; Lenzi, G.L.; Fazio, F.

    1986-01-01

    Regional CBF (rCBF) and regional cerebral blood volume (rCBV) were evaluated by N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-[123I]iodobenzyl-1, 3-propanediamine-2 HCl- and /sup 99m/TC-labeled red blood cells, respectively, and single-photon emission computerized tomography (SPECT) in a patient with focal cerebral ischemia. Sequential transmission computerized tomography (TCT) and SPECT functional data were compared with clinical findings to monitor the pathophysiological events occurring in stroke. A lack of correlation between rCBF-rCBV distributions and blood-brain barrier (BBB) breakdown was found in the acute phase. In the face of more prolonged alteration of BBB, as seen by TCT enhancement, a rapid evolution of transient phenomena such as luxury perfusion was shown by SPECT studies. Follow-up of the patient demonstrated a correlation between the neurological recovery and a parallel relative improvement of the cerebral perfusion

  2. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

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    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  3. 13-Methyltetradecanoic acid mitigates cerebral ischemia/reperfusion injury

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    Juan Yu

    2016-01-01

    Full Text Available 13-Methyltetradecanoic acid can stabilize cell membrane and have anti-inflammatory, antioxidant and anti-apoptotic effects. Previous studies mainly focused on peripheral nerve injury, but seldom on the central nervous system. We investigated whether these properties of 13-methyltetradecanoic acid have a neuroprotective effect on focal cerebral ischemia/reperfusion injury, and detected the expression of basic fibroblast growth factor and vascular endothelial growth factor. This study established rat models of middle cerebral artery occlusion/reperfusion injury by ischemia for 2 hours and reperfusion for 24 hours. At the beginning of reperfusion, 13-methyltetradecanoic acid 10, 40 or 80 mg/kg was injected into the tail vein. Results found that various doses of 13-methyltetradecanoic acid effectively reduced infarct volume, mitigate cerebral edema, and increased the mRNA and protein expression of basic fibroblast growth factor and vascular endothelial growth factor at 24 hours of reperfusion. The effect was most significant in the 13-methyltetradecanoic acid 40 and 80 mg/kg groups. The findings suggest that 13-methyltetradecanoic acid can relieve focal ischemia/reperfusion injury immediately after reperfusion, stimulate the upregulation of basic fibroblast growth factor and vascular endothelial growth factor to exert neuroprotective effects.

  4. Lateral intracerebroventricular injection of Apelin-13 inhibits apoptosis after cerebral ischemia/reperfusion injury

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    Xiao-ge Yan

    2015-01-01

    Full Text Available Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide, yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied. In this study, Apelin-13 (0.1 µg/g was injected into the lateral ventricle of middle cerebral artery occlusion model rats. TTC, TUNEL, and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group, infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group. Additionally, Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity. Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.

  5. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

    2013-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

  6. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    International Nuclear Information System (INIS)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases

  7. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  8. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2013-01-01

    Full Text Available Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

  9. Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

    International Nuclear Information System (INIS)

    Zhang Yuqing; Stevenson, Gail D.; Barber, Christy; Furenlid, Lars R.; Barrett, Harrison H.; Woolfenden, James M.; Zhao Ming; Liu Zhonglin

    2013-01-01

    Objectives: Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of 99m Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion. Methods: Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21–24 hr reperfusion. After i.v. injection of 99m Tc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis. Results: SPECT images showed that 99m Tc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92 ± 0.79. Fractional washout at 1 hr was 38.2 ± 4.5% of peak activity for left cerebral hot-spot areas and 80.9 ± 2.0% for remote control areas (P 99m Tc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

  10. MR perfusion/diffusion-weighted imaging of acute ischemia in an animal model with PET correlation

    International Nuclear Information System (INIS)

    Pickens, D.R.; Dawson, R.C.; Votaw, J.R.; Lorenz, C.H.; Holburn, G.E.; Price, R.R.

    1990-01-01

    This paper evaluates acute cerebral ischemia in an animal model with MR perfusion/diffusion-sensitive pulse sequences and to compare the results with PET regional cerebral blood flow (rCBF) measurements. An embolizing agent was injected into the proximal middle cerebral artery (MCA) of a dog, and this was followed by DSA. Next, the animal was imaged in a 1.5-T MR system with perfusion/diffusion-sensitive spin-echo pulse sequence. Then, PET imaging was performed with H 2 O 15 at corresponding levels of the brain

  11. Cerebral Ischemia Due to Traumatic Carotid Artery Dissection: Case Report

    OpenAIRE

    Deniz Kamacı Şener; Özlem Taşkapılıoğlu; Nermin Kelebek Girgin; Bahattin Hakyemez; Mustafa Bakar; Yakup Tomak

    2012-01-01

    Blunt injury to the neck region may lead to carotid artery dissection and cerebral ischemia. Blunt injury to carotid artery is not frequent but determination of the presence of trauma in the history of stroke patients will provide early diagnosis and treatment of them. In this article, a case with cerebral ischemia resulting from traumatic carotid artery dissection is presented and clinical findings, diagnostic procedures and choice of treatment are discussed in the light of the literature.

  12. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

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    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  13. A comparison study of PET, NMR, and CT imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    Babikian, V.L.; Ford, C.S.; Buonanno, F.S.; Kistler, J.P.; Ackerman, R.H.; Alpert, N.M.; Correia, J.A.; Johnson, K.A.; Buxton, R.B.

    1987-01-01

    Whether ischemia without infarction produces recognizable changes in relaxation times of ischemic but viable brain is an important, unresolved issue. Therefore, a study was initiated of patients with cerebral ischemia, using positron emission tomography (PET), NMR, and computed tomography (CT) to compare and contrast the pathophysiologic information provided by each and to study the issue of whether cerebral ischemia without infarction can be appreciated by proton NMR imaging. Here the initial results are reported. 4 refs.; 2 figs.; 1 table

  14. Cerebral Ischemia Due to Traumatic Carotid Artery Dissection: Case Report

    Directory of Open Access Journals (Sweden)

    Deniz Kamacı Şener

    2012-12-01

    Full Text Available Blunt injury to the neck region may lead to carotid artery dissection and cerebral ischemia. Blunt injury to carotid artery is not frequent but determination of the presence of trauma in the history of stroke patients will provide early diagnosis and treatment of them. In this article, a case with cerebral ischemia resulting from traumatic carotid artery dissection is presented and clinical findings, diagnostic procedures and choice of treatment are discussed in the light of the literature.

  15. Is chlormethiazole neuroprotective in experimental global cerebral ischemia? A microdialysis and behavioral study.

    Science.gov (United States)

    Thaminy, S; Reymann, J M; Heresbach, N; Allain, H; Lechat, P; Bentué-Ferrer, D

    1997-04-01

    Chlormethiazole, an anticonvulsive agent, has been shown to have a possible neuroprotective effect against cerebral ischemia. In addition, chlormethiazole inhibits methamphetamine-induced release of dopamine, protecting against this neurotransmitter's neurotoxicity. The aim of this work was to ascertain whether, in experimental cerebral ischemia, chlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whether it reduces ischemia-induced deficits in memory and learning. Histology for assessment of ischemic damage was a so included. The four-vessel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extracellular fluid obtained by microdialysis were assayed by high-performance liquid chromatography-electrochemical detection. The drug was administered either IP (50 mg/kg-1) or directly through the dialysis probe (30 microM) 80 min before ischemia. For the behavioral test and histology, the drug was given IP (100 mg/kg-1) 1 h postischemia. The results obtained did not demonstrate any statistically significant evidence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no variation in metabolite levels. Behavioral measures (learning, recall) were not changed appreciably by the treatment. We observed no significant cell protection in the hippocampus (CA1, CA1), striatum, and entorhinal cortex in animals treated with chlormethiazole. We conclude that, under our experimental conditions, chlormethiazole has little or no effect on the neurochemical, neurobehavioral, and histological consequences of global cerebral ischemia.

  16. Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Wang, Xifeng; Li, Gang; Shen, Wei

    2018-01-01

    Stroke is a leading cause of disability and death world-wide and there is currently a lack of effective treatments for acute stroke. D-Limonene is a common natural monocyclic monoterpene possessing various activities. The present study aimed to evaluate the therapeutic efficacy of D-limonene against ischemia-associated cerebral injury in hypertensive SHRsp rats. Although systolic blood pressure was not altered by ischemia, D-Limonene decreased the systolic blood pressure of SHRsp rats following stroke. Induction of stroke resulted in increased escape latency time, decreased time spent in the target quadrant in the probe trial, decreased capacity to distinguish between familiar objects and novel objects, and increased sensory neglect in the SHRsp rat, however these symptoms were significantly inhibited by D-limonene. D-limonene also decreased the cerebral infarct size in the SHRsp rats following stroke. D-Limonene markedly decreased the mRNA expression of interleukin-1β, monocyte chemoattractant protein-1 and cyclooxygenase-2 in SHRsp rats following stroke. The mRNA expression of vascular endothelial growth factor in the brain of SHRsp rats following stroke was significantly increased by D-Limonene. D-Limonene increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level, increased glutathione content and reduced the DHE-staining in SHRsp rats following stroke. Overall, inhibition of cerebral inflammation, vascular remodeling and antioxidant activities of D-Limonene may be involved in the protective effects against ischemia-induced damage in SHRsp rats. The present study identified D-Limonene as a potential therapeutic candidate for treatment of stroke-associated cerebral and vascular damage under conditions of hypertension.

  17. Protective effect of grifolin against brain injury in an acute cerebral ...

    African Journals Online (AJOL)

    Purpose: To evaluate the protective effects of grifolin against brain injury in an acute cerebral ischemia rat model. Methods: Rats were assigned to five groups: control, negative control, and grifolin (50, 100, and 200 mg/kg, p.o.) treated groups, which received the drug for 2 weeks. All the animals were sacrificed at the end of ...

  18. Adoptive regulatory T-cell therapy preserves systemic immune homeostasis after cerebral ischemia.

    Science.gov (United States)

    Li, Peiying; Mao, Leilei; Zhou, Guoqing; Leak, Rehana K; Sun, Bao-Liang; Chen, Jun; Hu, Xiaoming

    2013-12-01

    Cerebral ischemia has been shown to result in peripheral inflammatory responses followed by long-lasting immunosuppression. Our recent study demonstrated that intravenous delivery of regulatory T cells (Tregs) markedly protected against transient cerebral ischemia by suppressing neutrophil-derived matrix metallopeptidase 9 production in the periphery. However, the effect of Tregs on systemic inflammatory responses and immune status has not been fully characterized. Cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were isolated from donor animals by CD4 and CD25 double selection and transferred intravenously to ischemic recipients at 2 hours after middle cerebral artery occlusion. Animals were euthanized on different days after reperfusion. The effects of Tregs on systemic inflammation and immune status were evaluated using flow cytometry, ELISAs, and immunohistochemistry. Systemic administration of purified Tregs raises functional Tregs in the blood and peripheral organs, including spleen and lymph nodes. These exogenous Tregs remain in the blood and peripheral organs for ≥12 days. Functionally, Treg adoptive transfer markedly inhibits middle cerebral artery occlusion-induced elevation of inflammatory cytokines (interleukin-6 and tumor necrosis factor α) in the blood. Furthermore, Treg treatment corrects long-term lymphopenia and improves cellular immune functions after ischemic brain injury. As a result, Treg-treated animals exhibit decreased bacterial loads in the blood during recovery from cerebral ischemic attack. Treg treatment did not exacerbate poststroke immunosuppression. On the contrary, Treg-treated animals displayed improved immune status after focal cerebral ischemia.

  19. Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage.

    Science.gov (United States)

    Garry, Payashi S; Rowland, Matthew J; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W; Westbrook, Jon; Warnaby, Catherine E; Pattinson, Kyle T S

    2016-11-01

    Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed "early brain injury," with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Unblinded pilot study testing response to drug intervention. Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41-69 yr]; 11 women). IV sodium nitrite (10 μg/kg/min) for 1 hour. Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to -31%) (p = 0.006, multivariate analysis accounting for major confounds). Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient's susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage.

  20. [Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

    Science.gov (United States)

    Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

    2017-01-01

    To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

  1. Aerobic exercise combined with huwentoxin-I mitigates chronic cerebral ischemia injury

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    Hai-feng Mao

    2017-01-01

    Full Text Available Ca2+ channel blockers have been shown to protect neurons from ischemia, and aerobic exercise has significant protective effects on a variety of chronic diseases. The present study injected huwentoxin-I (HWTX-I, a spider peptide toxin that blocks Ca2+ channels, into the caudal vein of a chronic cerebral ischemia mouse model, once every 2 days, for a total of 15 injections. During this time, a subgroup of mice was subjected to treadmill exercise for 5 weeks. Results showed amelioration of cortical injury and improved neurological function in mice with chronic cerebral ischemia in the HWTX-I + aerobic exercise group. The combined effects of HWTX-I and exercise were superior to HWTX-I or aerobic exercise alone. HWTX-I effectively activated the Notch signal transduction pathway in brain tissue. Aerobic exercise up-regulated synaptophysin mRNA expression. These results demonstrated that aerobic exercise, in combination with HWTX-I, effectively relieved neuronal injury induced by chronic cerebral ischemia via the Notch signaling pathway and promoting synaptic regeneration.

  2. Neuroprotection of taurine through inhibition of 12/15 lipoxygenase pathway in cerebral ischemia of rats.

    Science.gov (United States)

    Zhang, Zhe; Yu, Rongbo; Cao, Lei

    2017-05-01

    Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. Taurine (Tau), an endogenous substance, possesses a number of cytoprotective properties. The aim of the present study was to examine the neuroprotective effect of Tau, through affecting 12/15 lipoxygenase (12/15-LOX) signal pathway in an acute permanent middle cerebral artery occlusion (MCAO) model of rats. Sprague-Dawley rats were randomly divided into 3 groups (n = 10), namely the sham-operated group, MCAO group and Tau group. Tau was intraperitoneally administrated immediately after cerebral ischemia. At 24 h after MCAO, neurological function score, brain water content and infarct volume were assessed. The expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK), and cytosolic phospholipase A2 (cPLA2) was measured by Western blot. Enzyme-linked immunosorbent assay was used to evaluate the inflammatory factors TNF-α, IL-1β and IL-6 in serum. Compared with MCAO group, taurine significantly improved neurological function and significantly reduced brain water content (p Taurine protected the brain from damage caused by MCAO; this effect may be through down-regulation of 12/15-LOX, p38 MAPK, and cPLA2.

  3. Effect of total flavonoids of Radix Ilicis pubescentis on cerebral ischemia reperfusion model

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    Xiaoli Yan

    2017-03-01

    Full Text Available This paper aims to observe the effects of total flavonoids of Radix Ilicis pubescentis on mouse model of cerebral ischemia reperfusion. Mice were orally given different doses of total flavonoids of Radix Ilicis pubescentis 10 d, and were administered once daily. On the tenth day after the administration of 1 h in mice after anesthesia, we used needle to hook the bilateral common carotid artery (CCA for 10 min, with 10 min ischemia reperfusion, 10 min ischemia. Then we restored their blood supply, copy the model of cerebral ischemia reperfusion; We then had all mice reperfused for 24 h, and then took their orbital blood samples and measured blood rheology. We quickly removed the brain, with half of the brain having sagittal incision. Then we fixed the brains and sectioned them to observe the pathological changes of brain cells in the hippocampus and cortex. We also measured the other half sample which was made of brain homogenate of NO, NOS, Na+-K+-, ATP enzyme Mg2+-ATPase and Ca2+-ATPase. Acupuncture needle hook occlusion of bilateral common carotid arteries can successfully establish the model of cerebral ischemia reperfusion. After comparing with the model mice, we concluded that Ilex pubescens flavonoids not only reduce damage to the brain nerve cells in the hippocampus and cortex, but also significantly reduce the content of NO in brain homogenate, the activity of nitric oxide synthase (NOS and increases ATP enzyme activity (P < 0.05, P < 0.01. In this way, cerebral ischemia reperfusion injury is improved. Different dosages of Ilex pubescens flavonoids on mouse cerebral ischemia reperfusion model have good effects.

  4. Clinical aspects and characteristics of the course of Parkinson’s disease with chronic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Voskresenskaya O.N.

    2012-06-01

    Full Text Available

    The article is devoted characteristics current of Parkinson’s disease with chronic cerebral ischemia. Objective: to study the clinical presentation and features of PD against cerebral ischemia. Methods. A total of 44 patients with a diagnosis of “Parkinson’s disease”, 20 of which were determined by accurate clinical and instrumental signs of chronic cerebral ischemia. Comparative characteristics of the neurological status, cognitive functions, some laboratory and instrumental data in the two groups of patients: Parkinson’s disease with a background of chronic ischemia of the brain and without it. Results. Statistically signifcant differences between groups are observed on the following variables: duration of illness, severity of depression, the concentration of glucose in the blood. Formed groups of signifcant difference in the severity of atherosclerosis of cerebral vessels. Conclusion. The data of the acceleration of the progression of Parkinson’s disease with chronic cerebral ischemia, as well as the more frequent occurrence of depression in this patient group.

  5. Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Tenjin, Hiroshi; Ueda, Satoshi; Mizukawa, Norihiko [Kyoto Prefectural Univ. of Medicine (Japan); and others

    1992-10-01

    Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69[+-]0.20, p<0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p<0.05). Clearly, OEF changes remarkably in the acute stage. (author).

  6. Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and 123I-IMP with acetazolamide test

    International Nuclear Information System (INIS)

    Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi; Suematsu, Katsumi.

    1989-01-01

    To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl 123 I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25∼50% stenosis), and severe degree(50%cerebral vasodilatory capacity was preserved at the normal level during the period of vasospasm. In eight patients with asymptomatic vasospasm (moderate degree), a transient limitation of cerebral vasodiratory capacity was observed between the 6th and 16th day after a rupture of the cerebral aneurysm. In five patients with symptomatic vasospasm resulting in reversible ischemia, a marked limitation of cerebral vasodilatory capacity was noted between the 7th and 15th day, and a delayed recovery of cerebral vasodilatory capacity was observed. This reversibility of cerebral vasodilatory capacity in patients with cerebral vasospasm suggests that a local decrease of purfusion pressure due to cerebral vasospasm causes compensatory vasodilation of intraparenchymal arteries and the vasodilatory reaction to acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.)

  7. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

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    Mohammad Allahtavakoli

    2011-01-01

    Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

  8. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia

    OpenAIRE

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-01-01

    Background The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. Results I...

  9. Neuroprotective effects of female sex steroids in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Drača Sanja

    2013-03-01

    Full Text Available The central and peripheral nervous system are important targets of sex steroids. Sex steroids affect the brain development and differentiation, and influence neuronal functions. Recent evidence emphasizes a striking sex-linked difference in brain damage after experimental stroke, as well as the efficacy of hormones in treating cerebral stroke injury. Several different models of cerebral ischemia have been utilized for hormone neuroprotection studies, including transient or permanent middle cerebral artery occlusion, transient global ischemia, and transient forebrain ischemia. Extensive experimental studies have shown that female sex steroids such as progesterone and 176-estradiol exert neuroprotective effects in the experimental models of stroke, although deleterious effects have also been reported. Also, a significance of numerous factors, including gender and age of experimental animals, localization of brain lesion, duration of ischemia and precise dose of steroids has been pointed out. There are multiple potential mechanisms that might be invoked to explain the beneficial effects of female sex steroids in brain injury, involving neuroprotection, anti-inflammatory properties, effects on vasculature and altered transcriptional regulation. A several clinical trials on the effects of sex hormones to traumatic brain injury have been performed, suggesting that hormone therapy may represent a new therapeutic tool to combat certain diseases, such as traumatic brain injury. Further basic science studies and randomized clinical trials are necessary to reveal a potential application of these molecules as a new therapeutic strategy.

  10. MR of experimental cerebral ischemia

    International Nuclear Information System (INIS)

    DeLaPaz, R.; Steinberg, G.; Rocklage, S.; Glover, G.H.

    1990-01-01

    This paper reports on MR imaging of cerebral ischemia and treatment with N-methyl-D-aspartate (NMDA) antagonists in an animal model. Forty-four New Zealand white rabbits underwent 1-hour transorbital ICA-MCA-ACA occlusion and pretreatment or immediate posttreatment with systemic dextromethorphan (DM, n = 14), dextrorphan (DX, n = 14), or normal saline (NS, n = 16). Serial MR studies (1.5 T) were performed 1--6 hours after occlusion with T1- and T2-weighted spinecho, IVIM (b = 1,352), gradient recalled acquisition in a steady-state, and chemical shift sequences (for magnetic susceptibility, T2* and T2') and DyDTPA-BMA intravenous contrast material (Salutar). Spatial correlation between MR findings, histologic findings (ischemic neuronal damage), and regional cerebral blood flow (microspheres) was done

  11. Effect of Panax notoginseng saponins on the content of IL-8 in serum after cerebral ischemia-reperfusion in rat

    International Nuclear Information System (INIS)

    He Wei; Zhu Zunping

    2002-01-01

    Objective: To investigate the effect of Panax notoginseng saponins (Pns) against cerebral ischemia-reperfusion injury. Methods: Focal cerebral ischemia-reperal ischemia-reperfusion model in rat was established by occlusion the middle cerebral artery for 2 h, after 3 h reperfusion. The serum concentration of IL-8 was detected with radioimmunoassay (RIA). Results: Png 50 mg·kg -1 ip, qd x 7d before MCAO decreased the serum content of IL-8 after ischemia-reperfusion. Conclusion: Pns has protective effect against cerebral ischemia-reperfusion injury by decreased the serum content of IL-8

  12. CT perfusion during delayed cerebral ischemia after subarachnoid hemorrhage: distinction between reversible ischemia and ischemia progressing to infarction

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, Charlotte H.P. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, PO Box 85500, Utrecht, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vos, Pieter C. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Schaaf, Irene C. van der; Velthuis, Birgitta K.; Dankbaar, Jan Willem [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vergouwen, Mervyn D.I.; Rinkel, Gabriel J.E. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, PO Box 85500, Utrecht, Utrecht (Netherlands)

    2015-09-15

    Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction. From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95 % confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve. In qualitative analyses of 33 included patients, 15 of 17 patients (88 %) with and 6 of 16 patients (38 %) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71 % (95%CI: 48-89 %) and NPV of 83 % (95%CI: 52-98 %) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63 % (95%CI: 41-81 %) and a NPV of 78 % (95%CI: 40-97 %) for infarction. CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation. (orig.)

  13. Toll-like receptors in cerebral ischemic inflammatory injury

    OpenAIRE

    Wang, Yan-Chun; Lin, Sen; Yang, Qing-Wu

    2011-01-01

    Abstract Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the...

  14. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    Science.gov (United States)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  15. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats.

    Science.gov (United States)

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2017-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blotting was performed to examine the change in levels of apoptosis-associated proteins in the injured brains. The results suggested that sanguinarine, an anti-inflammatory agent derived from the roots of Sanguinaria canadensis , improved the state of cerebral ischemia in a rat model. The data demonstrated that when rats were treated with sanguinarine prior to middle cerebral artery occlusion, the infarct volume was reduced significantly. The inflammatory factors tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured in sanguinarine and vehicle-treated groups using an enzyme-linked immunosorbent assay, and the expression levels of the three factors were significantly reduced following treatment with sanguinarine (Pprotective effect in cerebral ischemia, and that this effect is associated with the anti-inflammatory and anti-apoptotic properties of sanguinarine.

  16. Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and sup 123 I-IMP with acetazolamide test

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi (Nakamura Memorial Hospital, Sapporo (Japan)); Suematsu, Katsumi

    1989-11-01

    To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl {sup 123}I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25{approx}50% stenosis), and severe degree(50%cerebral vasodilatory capacity was preserved at the normal level during the period of vasospasm. In eight patients with asymptomatic vasospasm (moderate degree), a transient limitation of cerebral vasodiratory capacity was observed between the 6th and 16th day after a rupture of the cerebral aneurysm. In five patients with symptomatic vasospasm resulting in reversible ischemia, a marked limitation of cerebral vasodilatory capacity was noted between the 7th and 15th day, and a delayed recovery of cerebral vasodilatory capacity was observed. This reversibility of cerebral vasodilatory capacity in patients with cerebral vasospasm suggests that a local decrease of purfusion pressure due to cerebral vasospasm causes compensatory vasodilation of intraparenchymal arteries and the vasodilatory reaction to acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.).

  17. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

    Science.gov (United States)

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  18. Acute bowel ischemia: CT findings

    International Nuclear Information System (INIS)

    Angelelli, Giuseppe; Scardapane, Arnaldo; Memeo, Maurizio; Stabile Ianora, Amato Antonio; Rotondo, Antonio

    2004-01-01

    Acute bowel ischemia represents one of the most dramatic abdominal emergencies and, despite the fact it is more and more frequently observed in clinical practice, its mortality rate remains very high. In recent years Computed Tomography (CT) has proved to be a valid diagnostic tool in the evaluation of patients with acute abdominal syndrome and in the visualization of early signs of bowel ischemia. This paper reviews the aetiological and pathophysiological aspects as well as a broad spectrum of CT findings of this clinical condition

  19. Mixed models in cerebral ischemia study

    Directory of Open Access Journals (Sweden)

    Matheus Henrique Dal Molin Ribeiro

    2016-06-01

    Full Text Available The data modeling from longitudinal studies stands out in the current scientific scenario, especially in the areas of health and biological sciences, which induces a correlation between measurements for the same observed unit. Thus, the modeling of the intra-individual dependency is required through the choice of a covariance structure that is able to receive and accommodate the sample variability. However, the lack of methodology for correlated data analysis may result in an increased occurrence of type I or type II errors and underestimate/overestimate the standard errors of the model estimates. In the present study, a Gaussian mixed model was adopted for the variable response latency of an experiment investigating the memory deficits in animals subjected to cerebral ischemia when treated with fish oil (FO. The model parameters estimation was based on maximum likelihood methods. Based on the restricted likelihood ratio test and information criteria, the autoregressive covariance matrix was adopted for errors. The diagnostic analyses for the model were satisfactory, since basic assumptions and results obtained corroborate with biological evidence; that is, the effectiveness of the FO treatment to alleviate the cognitive effects caused by cerebral ischemia was found.

  20. Association of Automatically Quantified Total Blood Volume after Aneurysmal Subarachnoid Hemorrhage with Delayed Cerebral Ischemia

    NARCIS (Netherlands)

    Zijlstra, I. A.; Gathier, C. S.; Boers, A. M.; Marquering, H. A.; Slooter, A. J.; Velthuis, B. K.; Coert, B. A.; Verbaan, D.; van den Berg, R.; Rinkel, G. J.; Majoie, C. B.

    2016-01-01

    The total amount of extravasated blood after aneurysmal subarachnoid hemorrhage, assessed with semiquantitative methods such as the modified Fisher and Hijdra scales, is known to be a predictor of delayed cerebral ischemia. However, prediction rates of delayed cerebral ischemia are moderate, which

  1. Hemodynamic disturbances in cerebral ischemia; Correlation between positron emission tomographic and angiographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Tenjin, Hiroshi; Ueda, Satoshi; Mizukawa, Norihiko; Imahori, Yoshio; Hino, Akihiko; Ohmori, Yoshio [Kyoto Prefectural Univ. of Medicine (Japan); Nakahashi, Hisamitsu

    1993-04-01

    Proper treatment of ischemic stroke requires better understanding of cerebral hemodynamic changes. The hemodynamic changes associated with ischemia were measured using positron emission tomography and related to angiographic findings in the subacute and chronic stages of 17 ischemia patients who showed symptoms of main trunk stenosis of the internal carotid artery system. The hemodynamic factors, cerebral blood flow, cerebral blood volume, cerebral metabolic rate for oxygen, oxygen extraction fraction, and flow/volume ratio, were measured in regions of interest determined from the angiographic stenosis (over 50%) and compared in each stage. The cerebral blood flow and flow/volume ratio in the territory downstream of the main trunk stenosis and cerebral metabolic rate for oxygen in the whole cortex were decreased in the subacute stage. In the chronic stage, cerebral blood flow and flow/volume ratio decreased mainly in borderzone areas. (author).

  2. Inflammation and the neurovascular unit in the setting of focal cerebral ischemia.

    Science.gov (United States)

    del Zoppo, G J

    2009-02-06

    Responses to focal cerebral ischemia by neurons and adjacent microvessels are rapid, simultaneous, and topographically related. Recent observations indicate the simultaneous appearance of proteases by components of nearby microvessels that are also expressed by neurons in the ischemic territory, implying that the events could be coordinated. The structural relationship of neurons to their microvascular supply, the direct functional participation of glial cells, and the observation of a highly ordered microvessel-neuron response to ischemia suggest that these elements are arranged in and behave in a unitary fashion, the neurovascular unit. Their roles as a unit in the stimulation of cellular inflammation and the generation of inflammatory mediators during focal cerebral ischemia have not been explored yet. However, components of the neurovascular unit both generate and respond to these influences under the conditions of ischemia. Here we briefly explore the potential inter-relationships of the components of the neurovascular unit with respect to their potential roles in ischemia-induced inflammatory responses.

  3. Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia.

    Science.gov (United States)

    Chen, Tong; Ma, Zhanqiang; Zhu, Lingpeng; Jiang, Wenjiao; Wei, Tingting; Zhou, Rui; Luo, Fen; Zhang, Kai; Fu, Qiang; Ma, Chunhua; Yan, Tianhua

    2016-11-01

    The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor-interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-κB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis.

  4. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  5. [Mechanism of treatment effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats based on metabolomic approach].

    Science.gov (United States)

    Cao, Hui-Ting; Zhu, Hua-Xu; Zhang, Qi-Chun; Guo, Li-Wei

    2017-06-01

    The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry method(UPLC-Q-TOF/MS), Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database. The 20 potential biomarkers were found in the urine of rats with cerebral ischemia, which mainly involved in the neurotransmitter regulation, amino acid metabolism, energy metabolism, lipid metabolism and so on. Those metabolic pathways were disturbed in cerebral ischemia model rats, the principal component analysis showed that the normal and cerebral ischemia model is clearly distinguished, and the compound can be given to the normal state of change after HL, HQ, LQ administration. This study index the interpretation of cerebral ischemia rat metabolism group and mechanism, the embodiment of metabonomics can reflect the physiological and metabolic state, which can better reflect the traditional Chinese medicine as a whole view, system view and the features of multi ingredient synergistic or antagonistic effects. Copyright© by the Chinese Pharmaceutical Association.

  6. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  7. Effects of standard ethanolic extract from Erythrina velutina in acute cerebral ischemia in mice.

    Science.gov (United States)

    Rodrigues, Francisca Taciana Sousa; de Sousa, Caren Nádia Soares; Ximenes, Naiara Coelho; Almeida, Anália Barbosa; Cabral, Lucas Moraes; Patrocínio, Cláudio Felipe Vasconcelos; Silva, Aline Holanda; Leal, Luzia Kalyne Almeida Moreira; Honório Júnior, José Eduardo Ribeiro; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-12-01

    The objective of this study was to verify a possible neuroprotective effect of the ethanolic extract of Erythrina velutina (EEEV). Male Swiss mice were submitted to transient cerebral ischemia by occlusion of both carotid arteries for 30 min and treated for 5 days with EEEV (200 or 400 mg/kg) or Memantine (MEM) 10 mg/kg, with initiation of treatment 2 or 24 h after Ischemia. On the 6th day after the induction of ischemia, the animals were submitted to evaluation of locomotor activity and memory and then sacrificed. The brains were dissected for the removal of the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) for determination of amino acid concentrations. In the step down and Y-maze tests, ischemia caused damage to the animals and treatment with EEEV or MEM reversed this effect. The animals submitted to ischemia also showed memory deficit in the object recognition test, an effect that was reverted by EEEV400 and MEM10. Amino acid dosage showed an increase in excitatory amino acid concentrations in the PFC of the ischemic animals and this effect was reversed by the treatment with EEEV400/24H. Regarding the inhibitory amino acids, ischemia caused an increase of taurine in the PFC while treatment with MEM10/24H or EEEV400/24H reversed this effect. In HC, an increase in excitatory amino acids was also observed in ischemiated animals having treatment with EEEV200/2H or EEEV400/24H reversed this effect. Similar effect was also observed in the same area in relation to the inhibitory amino acids with treatment with MEM10/24H or EEEV400/24H. In the ST, ischemia was also able to cause an increase in excitatory amino acids that was reversed more efficiently by the treatments with MEM10/24H and EEEV200. Also in this area, an increase of taurine and GABA was observed and only the treatment with EEEV200/2H showed a reversion of this effect. In view of these findings, EEEV presents a neuroprotective effect possibly due to its action on amino acid

  8. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  9. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Chin-Yi Cheng

    2016-01-01

    Full Text Available Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs, including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

  10. Cost-effectiveness of CT angiography and perfusion imaging for delayed cerebral ischemia and vasospasm in aneurysmal subarachnoid hemorrhage

    NARCIS (Netherlands)

    P.C. Sanelli (Pina C.); A. Pandya; A.Z. Segal; A. Gupta; S. Hurtado-Rua; J. Ivanidze; K. Kesavabhotla; D. Mir; A.I. Mushlin; M.G.M. Hunink (Myriam)

    2014-01-01

    textabstractBACKGROUND AND PURPOSE: Delayed cerebral ischemia and vasospasm are significant complications following SAH leading to cerebral infarction, functional disability, and death. In recent years, CTA and CTP have been used to increase the detection of delayed cerebral ischemia and vasospasm.

  11. Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

    Science.gov (United States)

    Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

    2013-12-15

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (ppills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    2017-01-01

    Full Text Available Neurotrophin-3 (NT-3 is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

  13. Protective Effect of Extract of Folium Ginkgo on Repeated Cerebral Ischemia-Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the protective effect of extract of Folium Ginkgo (FGE) on repeated cerebral ischemia-reperfusion injury. Methods: The model in waking mice induced by repeated cerebral ischemia-reperfusion were used in the experiment to observe the effect of FGE on behavior, oxygen free radical metabolism and prostaglandin E2 (PGE2) content by step-through experiment, diving stand and colorimetric method. Results: FGE could obviously improve the learning ability and memory of model animals, and could lower obviously the content of malonyldialdehyde, nitric oxide and PGE2, restore the lowered activity of superoxide dismutase and catalase in cerebral tissue. Conclusion: FGE has highly protective effect against repeated ischemia-reperfusion injury, the mechanism might be related with its action on anti-lipid oxidatin, improve the activity of antioxidase and inhibit the producing of PGE2.

  14. Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Hui-Lin Wang

    2017-01-01

    Full Text Available Astragaloside IV (AST-IV is a principal component of Radix Astragali seu Hedysari (Huangqi and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P<0.05; seven studies for reducing the infarct volume (P<0.05; and three or two studies for reducing the brain water content and Evans blue leakage (P<0.05, respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

  15. Mitoxantrone Therapy for Acute Posterior Multifocal Placoid Pigment Epitheliopathy with Cerebral Vasculitis

    Directory of Open Access Journals (Sweden)

    Hélène Massé

    2009-01-01

    Full Text Available Purpose. To report favorable outcome of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE associated with cerebral vasculitis after treatment with immunosuppressive therapy by mitoxantrone. Design. Single case report. Method. A 22-year-old man presented with acute isolated bilateral loss of vision revealing APMPPE. Corticosteroid therapy was initiated and visual acuity gradually improved. Seventeen days later, visual function deteriorated again, associated with flu-like syndrome and severe headaches. A relapse of APMPPE was diagnosed, complicated with lymphocytic meningitis and cerebral ischemia. Intravenous therapy with mitoxantrone was performed in combination with methylprednisolone. Results. Headaches disappeared in a few days whereas visual acuity gradually improved and stabilized at 20/40 in the right eye and 20/32 in the left eye. No adverse event was observed. Clinical improvement was confirmed by magnetic resonance imaging. Conclusion. Cerebral vasculitis is the most severe complication of the extraocular manifestations of APMPEE. This diagnosis should be evoked when severe headaches or behavior disorder are associated with APMPEE.

  16. Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia.

    Science.gov (United States)

    Burrell, Christian; Avalon, Nicole E; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M Cristine; Freeman, William D

    2016-11-01

    Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.

  17. CSF and Serum Biomarkers Focusing on Cerebral Vasospasm and Ischemia after Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Carla S. Jung

    2013-01-01

    Full Text Available Delayed cerebral vasospasm (CVS and delayed cerebral ischemia (DCI remain severe complications after subarachnoid hemorrhage (SAH. Although focal changes in cerebral metabolism indicating ischemia are detectable by microdialysis, routinely used biomarkers are missing. We therefore sought to evaluate a panel of possible global markers in serum and cerebrospinal fluid (CSF of patients after SAH. CSF and serum of SAH patients were analyzed retrospectively. In CSF, levels of inhibitory, excitatory, and structural amino acids were detected by high-performance liquid chromatography (HPLC. In serum, neuron-specific enolase (NSE and S100B level were measured and examined in conjunction with CVS and DCI. CVS was detected by arteriography, and ischemic lesions were assessed by computed tomography (CT scans. All CSF amino acids were altered after SAH. CSF glutamate, glutamine, glycine, and histidine were significantly correlated with arteriographic CVS. CSF glutamate and serum S100B were significantly correlated with ischemic events after SAH; however, NSE did not correlate neither with ischemia nor with vasospasm. Glutamate, glutamine, glycine, and histidine might be used in CSF as markers for CVS. Glutamate also indicates ischemia. Serum S100B, but not NSE, is a suitable marker for ischemia. These results need to be validated in larger prospective cohorts.

  18. Outcomes of lower extremity bypass performed for acute limb ischemia.

    Science.gov (United States)

    Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

    2013-10-01

    Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function

  19. Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: clinicoanatomic correlations

    NARCIS (Netherlands)

    Hijdra, A.; van Gijn, J.; Stefanko, S.; van Dongen, K. J.; Vermeulen, M.; van Crevel, H.

    1986-01-01

    Fifty-seven of 176 prospectively studied patients with aneurysmal subarachnoid hemorrhage (SAH) developed delayed cerebral ischemia. Clinical features included hemispheric focal signs (13), decrease in level of consciousness (14), or both (30), and mutism (15). Forty-seven patients showed hypodense

  20. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  1. Sequential changes in ischemic edema following transient focal cerebral ischemia in rats; Magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Nagahiro, Shinji; Goto, Satoshi; Kogo, Kasei; Sumi, Minako; Takahashi, Mutsumasa; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    1994-07-01

    Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T[sub 2]-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T[sub 2] high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T[sub 2] high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema. (author).

  2. [Brain protection against cerebral ischemia].

    Science.gov (United States)

    Kitagawa, Kazuo

    2013-01-01

    Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.

  3. Protective Effect Of Bosentan In Experimental Cerebral Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Eser Ataş

    2013-02-01

    Full Text Available OBJECTIVE: In cerebral ischemia, there are many factors that start the events leading to cell death. These factors contain free radical production, excitotoxicity, sodium and calcium flow disruption, enzymatic changes, stimulation of the inflamatuar process, the activation of platelets and leukocytes, delayed coagulation, endothelial dysfunction and endothelin (ET release. Bosentan is the competitive antagonist of endothelin receptors; ETA and ETB. The aim of this study is to determine whether the protective effects of bosentan in experimental cerebral ischemia reperfusion injury. MATERIAL and METHODS: In this study, after ischemia-reperfusion procedure, bosentan molecule was regularly given to rats for 5 days. The brain tissues of decapitated rats were histopathologically examined. The levels of oxidant and antioxidant were determined in these brain tissues. RESULTS: It was observed that antioxidant levels and histopathological examinations were in rats given bosentan better than control group rats. CONCLUSION: In conclusion, this study has showed that bosentan may be an agent which could reduce negative effects resulting from neuronal death associated with ischemic stroke.

  4. Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy

    Directory of Open Access Journals (Sweden)

    Ming-Shuo Sun

    2018-01-01

    Full Text Available Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury has been found to play a key role in the process. Free radicals lead to protein dysfunction, DNA damage, and lipid peroxidation, resulting in cell death. Additionally, free radical damage has a strong connection with inducing hemorrhagic transformation and cerebral edema, which are the major complications of revascularization therapy, and mainly influencing neurological outcomes due to the disruption of the blood-brain barrier. In order to get a better clinical prognosis, more and more studies focus on the pharmaceutical and nonpharmaceutical neuroprotective therapies against free radical damage. This review discusses the pathological mechanisms of free radicals in ischemia-reperfusion injury and adjunctive neuroprotective therapies combined with revascularization therapy against free radical damage.

  5. Effect of NMDA Receptor Antagonist on Local Cerebral Glucose Metabolic Rate in Focal Cerebral Ischemia

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Hong, Seung Bong; Yoon, Byung Woo

    1995-01-01

    There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 posttreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

  6. Salvinorin A preserves cerebral pial artery autoregulation after forebrain ischemia via the PI3K/AKT/cGMP pathway

    Directory of Open Access Journals (Sweden)

    H.P. Dong

    2018-03-01

    Full Text Available This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR control group received DMSO (1 µL/kg immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg and LY294002 (10 µM, L-NAME (10 μM, or norbinaltorphimine (norBIN, 1 μM after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF were also measured. The phosphorylation of AKT (p-AKT was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.

  7. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Energy Technology Data Exchange (ETDEWEB)

    Khodanovich, M. Yu., E-mail: khodanovich@mail.tsu.ru [Tomsk State University, Research Institute of Biology and Biophysics, Laboratory of Neurobiology (Russian Federation)

    2015-11-17

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  8. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Science.gov (United States)

    Khodanovich, M. Yu.

    2015-11-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  9. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    International Nuclear Information System (INIS)

    Khodanovich, M. Yu.

    2015-01-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors

  10. Nootropics in a Complex Therapy of Chronic Cerebral Ischemia

    OpenAIRE

    Chekman, I.S.; Belenichev, I.F.; Demchenko, A.V.; Bobrova, V.I.; Kucherenko, L.I.; Gorchakova, N.A.; Bukhtiyarova, N.V.

    2014-01-01

    Clinical and pharmacological characteristics of nootropics — one of the most productive groups of neuropsychotropic drugs, are considered. Classification of nootropics based on the main mechanism of action is constructed. The examples of clinical use of drugs in patients with chronic cerebral ischemia are presented.

  11. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

    Directory of Open Access Journals (Sweden)

    Yisong Qian

    2016-08-01

    Full Text Available Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC staining, neuronal damage was assessed by Haematoxylin Eosin (H&E staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  12. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model.

    Science.gov (United States)

    Qian, Yisong; Tang, Xuzhen; Guan, Teng; Li, Yunman; Sun, Hongbin

    2016-08-19

    Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  13. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    OpenAIRE

    Zun-Jing Liu; Wei Liu; Lei Liu; Cheng Xiao; Yu Wang; Jing-Song Jiao

    2013-01-01

    Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPAR ? agonist in that it upregulated PPAR ? expression and PPAR ? -PPRE binding activity. Administration of curcumin markedly dec...

  14. Nootropics in a Complex Therapy of Chronic Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Chekman, I.S.

    2014-07-01

    Full Text Available Clinical and pharmacological characteristics of nootropics — one of the most productive groups of neuropsychotropic drugs, are considered. Classification of nootropics based on the main mechanism of action is constructed. The examples of clinical use of drugs in patients with chronic cerebral ischemia are presented.

  15. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.

    2005-01-01

    -vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha...

  16. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    International Nuclear Information System (INIS)

    Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Hirakawa, Kimiyoshi

    1987-01-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo 1 H- and 31 P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the 1 H-MRIs and 31 P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the 31 P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the 31 P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the 31 P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly. (J.P.N.)

  17. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, S; Higuchi, T; Horikawa, Y; Tanaka, C; Hirakawa, K

    1987-02-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo /sup 1/H- and /sup 31/P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the /sup 1/H-MRIs and /sup 31/P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the /sup 31/P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the /sup 31/P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the /sup 31/P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly.

  18. Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

    Science.gov (United States)

    Kim, J A; Rosenthal, E S; Biswal, S; Zafar, S; Shenoy, A V; O'Connor, K L; Bechek, S C; Valdery Moura, J; Shafi, M M; Patel, A B; Cash, S S; Westover, M B

    2017-06-01

    To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. Changes in brain levels of N-acylethanolamines and 2-arachidonoylglycerol in focal cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Degn, Matilda; Lambertsen, Kate L; Petersen, Gitte

    2007-01-01

    cerebral ischemia and endogenous NAEs. Over the first 24 h after induction of permanent middle cerebral artery occlusion, we observed a time-dependent increase in all the investigated NAEs, except for anandamide. Moreover, we found an accumulation of 2-AG at 4 h that returned to basal level 12 h after.......5 h before arterial occlusion decreased the infarct volume in our model system. Our results suggest that NAEs and 2-AG may be involved in regulation of neuroprotection during focal cerebral ischemia in mice....

  20. Impairment of neuropsychological function in patients with hemodynamic cerebral ischemia and efficacy of bypass surgery

    International Nuclear Information System (INIS)

    Sasoh, Masayuki

    1999-01-01

    In order to evaluate the relation between neuropsychological functions and hemodynamic cerebral ischemia, the author analyzed neuropsychological examination and the cerebral blood flow and metabolism of patients before and after bypass surgery. Twenty-five patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had one or more episodes of focal cerebral ischemia due to unilateral internal carotid or middle cerebral artery occlusion. Computerized tomography scans either were normal or showed evidence of watershed infarction. Based on these criteria, superficial temporal artery-proximal middle cerebral artery anastomosis was performed. The baseline cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO 2 ) and cerebrovascular reserve capacity (CVRC) were studied using positron emission computerized tomography (PET) and the acetazolamide test. Neuropsychological evaluations including Hasegawa Dementia Scale-Revised, Mini-Mental State and Wechsler Adult Intelligence Scale-Revised (WAIS-R), and PET study were completed one month after the last ischemic event and 3-6 months after the operation. A significant negative correlation was observed between OEF and neuropsychological functions. Postoperative neuropsychological functions showed significant improvement. Significant correlations were observed for ΔWAIS-R (preoperative WAIS-R postoperative WAIS-R) versus preoperative CMRO 2 (r=0.52), for ΔWAIS-R versus preoperative OEF (r=0.47). In view of these findings, the author concludes that elevation of OEF impairs neuropsychological functions and bypass surgery improves neuropsychological functions in patients with normal CMRO 2 and elevated OEF. (author)

  1. Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ding-I Yang

    2011-10-01

    Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

  2. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

    Science.gov (United States)

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

  3. Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

    Science.gov (United States)

    Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

    2013-12-01

    There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

  4. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, Iris; Reith, Wolfgang [Department of Neuroradiology, Saarland University Clinic, Homburg/Saar (Germany)

    2002-07-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  5. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Grunwald, Iris; Reith, Wolfgang

    2002-01-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  6. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia

    OpenAIRE

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potent...

  7. Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.

    Science.gov (United States)

    Jeong, Ji Heun; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Dong Kwan; Kim, Jwa-Jin; Han, Seung-Yun

    2016-11-01

    Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

  8. The influence of stachydrine hydrochloride on the reperfusion model of mice with repetitive cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mingsan Miao

    2017-03-01

    Full Text Available To study the influence of stachydrine hydrochloride on the inflammatory cytokines and tissue morphology of the re-perfusion model of mice with repetitive cerebral ischemia and probe into the protection mechanism of stachydrine hydrochloride for cerebral ischemia reperfusion impairment. Build a repetitive cerebral ischemia reperfusion model by first blocking the common carotid artery on both sides for 10 min, then resuming perfusion for 10 min and then blocking the common carotid artery on both sides again for 10 min. Before the operation, all the mice in the Nimodipine group, and the big, medium and small stachydrine hydrochloride dose groups were given corresponding gastric perfusion, the mice in the sham operation group and the modeled groups were at the same time given 0.5% sodium carboxymethyl cellulose for gastric perfusion of the same volume. The medicine was fed daily for 7 consecutive days. The model was built 1 h after the last feed and the perfusion continued for 24 h after the operation. Then the death rate of the mice was calculated. The mouse brains were taken out to test the ICAM-1 level and the TNF-α level, and the serum was taken out to test the NSE level and the MPO level. The tissue morphology changes were also observed. All the repetitive cerebral ischemia reperfusion models were successfully duplicated. The stachydrine hydrochloride in all the dose groups significantly reduced the death rates of big and small mice, reduced the level of ICAM-1 and the level of TNF-α in the brain tissues and the NSE level and the MPO level in the serum, significantly alleviating the pathological impairment in the hippocampus. Stachydrine hydrochloride can significantly reduce the death rate of mice, improve the pathological changes in the hippocampus, inhibit inflammatory reactions after ischemia, thus reducing the re-perfusion impairment after cerebral ischemia.

  9. Neuroprotective Effect of Xueshuantong for Injection (Lyophilized in Transient and Permanent Rat Cerebral Ischemia Model

    Directory of Open Access Journals (Sweden)

    Xumei Wang

    2015-01-01

    Full Text Available Xueshuantong for Injection (Lyophilized (XST, a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk., is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx 6-toll-like receptor (TLR 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1β (IL-1β, IL-17, IL-23p19, tumor necrosis factor-α (TNFα, and inducible nitric oxide synthase (iNOS in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx 6-toll-like receptor (TLR 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats’ weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.

  10. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats

    OpenAIRE

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2016-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blot...

  11. Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

    DEFF Research Database (Denmark)

    Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard

    2014-01-01

    BACKGROUND: Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB...... and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...

  12. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

    Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

  13. Role of unphosphorylated transcription factor STAT3 in late cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Samraj, Ajoy K; Müller, Anne H; Grell, Anne-Sofie

    2014-01-01

    Molecular mechanisms behind increased cerebral vasospasm and local inflammation in late cerebral ischemia after subarachnoid hemorrhage (SAH) are poorly elucidated. Using system biology tools and experimental SAH models, we have identified signal transducer and activator of transcription 3 (STAT3...

  14. Fatty Acid Methyl Esters and Solutol HS 15 Confer Neuroprotection After Focal and Global Cerebral Ischemia

    OpenAIRE

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L.; Neumann, Jake T.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    We previously showed that palmitic methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Soluto...

  15. Scutellarin Attenuates Microglia-Mediated Neuroinflammation and Promotes Astrogliosis in Cerebral Ischemia - A Therapeutic Consideration.

    Science.gov (United States)

    Wu, Chun-Yun; Fang, Ming; Karthikeyan, Aparna; Yuan, Yun; Ling, Eng-Ang

    2017-01-01

    Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia, which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions. Here, we review the roles of activated microglia and reactive astrocytes in brain diseases with special reference to cerebral ischemia, and the effects of scutellarin, a Chinese herbal extract on both glial cells. We first reviewed the close spatial relation between activated microglia and reactive astrocytes as it suggests that both glial cells work in concert for tissue reconstruction and repair. Secondly, we have identified scutellarin as a putative therapeutic agent as it has been found to not only suppress microglial activation thus ameliorating neuroinflammation, but also enhance astrocytic reaction. In the latter, scutellarin amplified the astrocytic reaction by upregulating the expression of neurotrophic factors among others thus indicating its neuroprotective role. Remarkably, the effects of scutellarin on reactive astrocytes were mediated by activated microglia supporting a functional "cross-talk" between the two glial types. This review highlights some of our recent findings taking into consideration of others demonstrating the beneficial effects of scutellarin on both glial cell types in cerebral ischemia as manifested by improvement of neurological functions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

    Science.gov (United States)

    Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

    2013-07-21

    It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

  17. Impairment of neuropsychological function in patients with hemodynamic cerebral ischemia and efficacy of bypass surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sasoh, Masayuki [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1999-08-01

    In order to evaluate the relation between neuropsychological functions and hemodynamic cerebral ischemia, the author analyzed neuropsychological examination and the cerebral blood flow and metabolism of patients before and after bypass surgery. Twenty-five patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had one or more episodes of focal cerebral ischemia due to unilateral internal carotid or middle cerebral artery occlusion. Computerized tomography scans either were normal or showed evidence of watershed infarction. Based on these criteria, superficial temporal artery-proximal middle cerebral artery anastomosis was performed. The baseline cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO{sub 2}) and cerebrovascular reserve capacity (CVRC) were studied using positron emission computerized tomography (PET) and the acetazolamide test. Neuropsychological evaluations including Hasegawa Dementia Scale-Revised, Mini-Mental State and Wechsler Adult Intelligence Scale-Revised (WAIS-R), and PET study were completed one month after the last ischemic event and 3-6 months after the operation. A significant negative correlation was observed between OEF and neuropsychological functions. Postoperative neuropsychological functions showed significant improvement. Significant correlations were observed for {delta}WAIS-R (preoperative WAIS-R postoperative WAIS-R) versus preoperative CMRO{sub 2} (r=0.52), for {delta}WAIS-R versus preoperative OEF (r=0.47). In view of these findings, the author concludes that elevation of OEF impairs neuropsychological functions and bypass surgery improves neuropsychological functions in patients with normal CMRO{sub 2} and elevated OEF. (author)

  18. Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mustafa Guven

    2015-04-01

    Conclusion:Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future.

  19. Proposal for a universal definition of cerebral infarction.

    Science.gov (United States)

    Saver, Jeffrey L

    2008-11-01

    Cerebral infarction is a leading cause of disability and death worldwide but has no uniform international definition. Recent diagnostic advances have revised fundamental concepts in cerebral and cardiac ischemia. Cardiologists, already possessed of a nosologic framework distinguishing myocardial infarction from unstable angina on the basis of tissue state, promulgated a new "universal" tissue definition of myocardial infarction incorporating insights afforded by assays of cardiac troponin, a serum biomarker exquisitely sensitive to myocardial injury. Concurrently, vascular neurologists proposed a new tissue, rather than time, criterion to distinguish transient ischemia attack from cerebral infarction, responding to perspectives provided by diffusion MRI and cerebral blood volume CT, imaging biomarkers highly sensitive to neuronal injury. To complete this conceptual realignment, vascular neurology must now advance a clear, uniform, and operationalizable tissue definition of cerebral infarction. This review proposes cerebral infarction be defined as brain or retinal cell death due to prolonged ischemia. This definition categorizes both pannecrosis and neuronal dropout ("complete" and "incomplete" infarcts in classic neuropathologic terminology) as cerebral infarcts. Making the presence of any neuronal or glial cell death essential yields a definition of cerebral infarction that has high relevance to patients, physicians, and policymakers; is more easily applied in clinical practice; fosters action in acute care; harmonizes with myocardial ischemia classification; and focuses diagnostic evaluation on the cause of brain ischemia and the occurrence of end organ injury. The term cerebral infarction should be used when there is evidence of brain or retinal cell death due to cerebral ischemia.

  20. Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

    2012-12-01

    Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

  1. Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

    Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

  2. Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana; Yavagal, Dileep R

    2013-01-01

    Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in future.

  3. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

  4. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

    2014-01-01

    BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (Mit...... the ETBR mRNA and protein levels. It also significantly reduced the ETBR mediated cerebrovascular contractility. Detailed analysis indicated that ERK1/2 mediated phosphorylation of Sp1 might be essential for ETBR transcription. CONCLUSION: Transcription factor Sp1 regulates the ETBR mediated...

  5. The role of the endoplasmic reticulum stress response following cerebral ischemia.

    Science.gov (United States)

    Hadley, Gina; Neuhaus, Ain A; Couch, Yvonne; Beard, Daniel J; Adriaanse, Bryan A; Vekrellis, Kostas; DeLuca, Gabriele C; Papadakis, Michalis; Sutherland, Brad A; Buchan, Alastair M

    2018-06-01

    Background Cornu ammonis 3 (CA3) hippocampal neurons are resistant to global ischemia, whereas cornu ammonis (CA1) 1 neurons are vulnerable. Hamartin expression in CA3 neurons mediates this endogenous resistance via productive autophagy. Neurons lacking hamartin demonstrate exacerbated endoplasmic reticulum stress and increased cell death. We investigated endoplasmic reticulum stress responses in CA1 and CA3 regions following global cerebral ischemia, and whether pharmacological modulation of endoplasmic reticulum stress or autophagy altered neuronal viability . Methods In vivo: male Wistar rats underwent sham or 10 min of transient global cerebral ischemia. CA1 and CA3 areas were microdissected and endoplasmic reticulum stress protein expression quantified at 3 h and 12 h of reperfusion. In vitro: primary neuronal cultures (E18 Wistar rat embryos) were exposed to 2 h of oxygen and glucose deprivation or normoxia in the presence of an endoplasmic reticulum stress inducer (thapsigargin or tunicamycin), an endoplasmic reticulum stress inhibitor (salubrinal or 4-phenylbutyric acid), an autophagy inducer ([4'-(N-diethylamino) butyl]-2-chlorophenoxazine (10-NCP)) or autophagy inhibitor (3-methyladenine). Results In vivo, decreased endoplasmic reticulum stress protein expression (phospho-eIF2α and ATF4) was observed at 3 h of reperfusion in CA3 neurons following ischemia, and increased in CA1 neurons at 12 h of reperfusion. In vitro, endoplasmic reticulum stress inducers and high doses of the endoplasmic reticulum stress inhibitors also increased cell death. Both induction and inhibition of autophagy also increased cell death. Conclusion Endoplasmic reticulum stress is associated with neuronal cell death following ischemia. Neither reduction of endoplasmic reticulum stress nor induction of autophagy demonstrated neuroprotection in vitro, highlighting their complex role in neuronal biology following ischemia.

  6. Symptomatic Cerebral Vasospasm and Delayed Cerebral Ischemia Following Transsphenoidal Resection of a Craniopharyngioma.

    Science.gov (United States)

    Ricarte, Irapuá Ferreira; Funchal, Bruno F; Miranda Alves, Maramélia A; Gomes, Daniela L; Valiente, Raul A; Carvalho, Flávio A; Silva, Gisele S

    2015-09-01

    Vasospasm has been rarely described as a complication associated with craniopharyngioma surgery. Herein we describe a patient who developed symptomatic vasospasm and delayed cerebral ischemia after transsphenoidal surgery for a craniopharyngioma. A 67-year-old woman became drowsy 2 weeks after a transsphenoidal resection of a craniopharyngioma. A head computed tomography (CT) was unremarkable except for postoperative findings. Electroencephalogram and laboratory studies were within the normal limits. A repeated CT scan 48 hours after the initial symptoms showed bilateral infarcts in the territory of the anterior cerebral arteries (ACA). Transcranial Doppler (TCD) showed increased blood flow velocities in both anterior cerebral arteries (169 cm/second in the left ACA and 145 cm/second in the right ACA) and right middle cerebral artery (164 cm/second) compatible with vasospasm. A CT angiography confirmed the findings. She was treated with induced hypertension and her level of consciousness improved. TCD velocities normalized after 2 weeks. Cerebral vasospasm should be considered in the differential diagnosis of patients with altered neurologic status in the postoperative period following a craniopharyngioma resection. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke

    International Nuclear Information System (INIS)

    Klotz, Ernst; Koenig, Matthias

    1999-01-01

    Objective: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. Methods and material: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. Results: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P<0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P<0.05). Conclusion: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower

  8. Brain scan in cerebral ischemia. An experimental model in the rat

    International Nuclear Information System (INIS)

    Turner, J.H.

    1975-01-01

    A rapid embolic method for consistent induction of stroke in the rat is described. Brain scans were performed using a micro-pinhole collimator system, and the value of the model for studies in localization of radiopharmaceuticals in cerebral ischemia is demonstrated

  9. Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats.

    Science.gov (United States)

    Liang, Hao; Liu, Ping; Wang, Yunshan; Song, Shuliang; Ji, Aiguo

    2011-07-15

    The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (pagent. Further studies are warranted to assess the efficacy and safety of LHAE in patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

  10. Transient cerebral ischemia induces albumin expression in microglia only in the CA1 region of the gerbil hippocampus.

    Science.gov (United States)

    Park, Joon Ha; Park, Jin-A; Ahn, Ji Hyeon; Kim, Yang Hee; Kang, Il Jun; Won, Moo-Ho; Lee, Choong-Hyun

    2017-07-01

    Albumin, the most abundant plasma protein, is known to exhibit a neuroprotective effect in animal models of focal and global cerebral ischemia. In the present study, the expression and immunoreactivity of albumin was examined in the hippocampus following 5 min of transient cerebral ischemia in gerbils. Albumin immunoreactivity was observed in microglia of the CA1 hippocampal region 2 days post‑ischemic insult, and it was significantly increased at 4 days following ischemia-reperfusion. In addition, at 4 days post‑ischemic insult, albumin‑immunoreactive microglia were abundant in the stratum pyramidale of the CA1 region. The present results demonstrated that albumin was newly expressed post‑injury in microglia in the CA1 region, suggesting ischemia‑induced neuronal loss. Albumin expression may therefore be associated with ischemia‑induced delayed neuronal death in the CA1 region following transient cerebral ischemia.

  11. Assessment and diagnosis of acute bowel ischemia with multidetector computed tomography (MDCT)

    International Nuclear Information System (INIS)

    Sojka, B.; Gieszczyk-Paraniak, B.; Gibinska, J.; Konopka, M.

    2008-01-01

    Acute bowel ischemia (ABT) is a life-threatening condition which most often effects elderly patients. It requires an intensive treatment and quick diagnosis. Unfortunately ABI manifested not only by specific but also various nonspecific clinical or laboratory finding. The radiological symptoms of the bowel ischemia are also differentiated and often nonspecific while the specific findings are rather uncommon.That is why the knowledge of the bowel ischemia pathogenesis and possible CT findings is so important for the correct diagnosis. The our paper, we present the radiological findings of the acute bowel ischemia based on the analysis of the patients' abdominal -CT examination. The purpose of our study is to MDCT in patients with acute bowel ischemia. The material of this study consists of four computer tomography examinations - three of those an angio-CT and one abdominal - in patients with acute abdomen symptoms. The result revealed the mesenteric thrombosis in two cases, and mesenteric artery stenosis in one case. In one case, the thrombus was present in the abdominal aorta. In conclusion, we claim that the MDCT should be the modality of choice for the diagnosis of the acute bowel ischemia. (author)

  12. Acute testicular ischemia caused by incarcerated inguinal hernia.

    Science.gov (United States)

    Orth, Robert C; Towbin, Alexander J

    2012-02-01

    Acute testicular ischemia caused by an incarcerated inguinal hernia usually affects infants. There are few reports of diagnosis using US, and the effect of long-standing reducible hernias on testicular growth in infants and children is unknown. The objectives of this study were to determine the incidence of testicular ischemia secondary to an incarcerated inguinal hernia at scrotal sonography and to determine the effect on testicular size at diagnosis. A hospital database was used to locate scrotal sonography examinations documenting an inguinal hernia, and images were reviewed for signs of testicular ischemia. Testicular volumes were compared using the Wilcoxon signed rank test. A total of 147 patients were identified with an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%) had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and showed a statistically significant increase in ipsilateral testicular size compared to the contralateral testicle (P = 0.012). Patients without testicular ischemia did not show a significant difference in testicular size, regardless of patient age. An incarcerated inguinal hernia should be considered as a cause of acute testicular ischemia in infants younger than 6 months of age.

  13. CT findings of early acute cerebral infarction

    International Nuclear Information System (INIS)

    Kim, Tae Hoon; Choi, Woo Suk; Ryu, Kyung Nam

    1992-01-01

    The CT findings of the acute cerebral infarction are well known. However the CT findings of early stroke within 24 hours of the onset have not been sufficiently reported. The purpose of this study is to evaluate early acute cerebral infarction on CT within 24 hours after ictus. The early and accurate CT diagnosis could lead to the appropriate therapy and improved outcome of the patients. Authors retrospectively analyzed 16 patients with early acute cerebral infarction. Acute cerebral infarction was confirmed by follow-up CT in 11 patients, SPECT in 4 patients, and MRI in 1 patient. The CT findings of early acute cerebral infarction include effacement of cortical sulci or cistern (n = 16, 100%), hyperattenuation of MCA (n = 3), obscuration of lentiform nucleus (n = 6), loss of insular ribbon (n = 6) and subtle low density in hemisphere (n = 5). The most frequent finding was effacement of cortical sulci in our study, and it was thought to be the most important sign of early acute cerebral infarction

  14. CT findings of early acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hoon; Choi, Woo Suk; Ryu, Kyung Nam [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1992-11-15

    The CT findings of the acute cerebral infarction are well known. However the CT findings of early stroke within 24 hours of the onset have not been sufficiently reported. The purpose of this study is to evaluate early acute cerebral infarction on CT within 24 hours after ictus. The early and accurate CT diagnosis could lead to the appropriate therapy and improved outcome of the patients. Authors retrospectively analyzed 16 patients with early acute cerebral infarction. Acute cerebral infarction was confirmed by follow-up CT in 11 patients, SPECT in 4 patients, and MRI in 1 patient. The CT findings of early acute cerebral infarction include effacement of cortical sulci or cistern (n = 16, 100%), hyperattenuation of MCA (n = 3), obscuration of lentiform nucleus (n = 6), loss of insular ribbon (n = 6) and subtle low density in hemisphere (n = 5). The most frequent finding was effacement of cortical sulci in our study, and it was thought to be the most important sign of early acute cerebral infarction.

  15. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

    Science.gov (United States)

    Panickar, Kiran S; Jang, Saebyeol

    2013-08-01

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

  16. Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do.

    Science.gov (United States)

    Wickering, Ellis; Gaspard, Nicolas; Zafar, Sahar; Moura, Valdery J; Biswal, Siddharth; Bechek, Sophia; OʼConnor, Kathryn; Rosenthal, Eric S; Westover, M Brandon

    2016-06-01

    The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha-delta ratio and relative alpha variability are needed before an automated EEG-based early delayed cerebral ischemia detection system is ready for clinical use.

  17. Acute limb ischemia in cancer patients: should we surgically intervene?

    LENUS (Irish Health Repository)

    Tsang, Julian S

    2012-02-01

    BACKGROUND: Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS: Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS: Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION: Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.

  18. Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats.

    Science.gov (United States)

    Fei, Yu-Xiang; Wang, Si-Qi; Yang, Li-Jian; Qiu, Yan-Ying; Li, Yi-Ze; Liu, Wen-Yuan; Xi, Tao; Fang, Wei-Rong; Li, Yun-Man

    2017-07-31

    Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO 2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism. Following induction of cerebral ischemia in rats by permanent middle cerebral artery occlusion (pMCAO). Neurological defect score, cerebral blood flow, infarct size, and brain edema were measured to evaluate the injury. Arteriovenous shunt thrombosis model and adenosine 5'-diphosphate (ADP) induced acute pulmonary embolism model were conducted to estimate the antithrombotic effect of SCED. In order to investigate the effects of SCED on platelet aggregation, rat platelet-rich-plasma (PRP) were incubated with SCED prior to the addition of the stimuli (ADP or 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)). Aggregation was monitored in a light transmission aggregometer. Inhibitory effect of SCED on thromboxane A2 (TXA 2 ) release was detected by ELISA kit. Phospholipase C (PLC)/ Protein kinase C (PKC) signaling pathway was analyzed by a Western blot technique. The effect of the SCED was also studied in vivo on bleeding time in mice. SCED improved the neurological defect score, increased cerebral blood flow, reduced infarct size and alleviated brain edema in rats exposed to pMCAO. After administration of SCED, thrombosis formation in arteriovenous shunt was inhibited and recovery time in pulmonary embolism was shortened. The inhibitory effect of SCED on platelet activation was further confirmed by TXB 2 ELISA kit and Western blot analysis of PLC

  19. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    Science.gov (United States)

    Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2010-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

  20. Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Ryo Tamaki

    2017-01-01

    Full Text Available Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or “enriched environment” as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression (CSD induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation (Sham, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs (CSD + 2-VO. As an additional control, 15 naïve rats received no intervention except 5-bromo-2′-deoxyuridine (BrdU treatment for 7 days. Sagittal brain slices (40 μm thick were co-stained for BrdU and doublecortin (DCX; new immature neuronal cells on day 9 or NeuN (new mature neuronal cells on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD + 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in naïve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD + 2-VO is a direct effect of ischemia, rather than of CSD alone.

  1. [The pathogenetic prerequisites for the application of the general magnetic therapy in the children presenting with cerebral ischemia].

    Science.gov (United States)

    Denisova, O I; Davydkin, N F; Kulikov, A G

    2014-01-01

    This article presents the analysis of the current literature and the original data of the authors providing the rationale for the use of magnetic therapy for the treatment of the children presenting with cerebral ischemia taking into consideration pathogenesis of this disease. It is demonstrated that the application of the general magnetic field decreases the tone of the cerebral vessels and improves blood flow to the brain which increases resistance to cerebral hypoxia. The results of investigations into the microcirculatory changes and liquor dynamics in conjunction with the ventriculometric measurements give evidence of the effectiveness of the combined treatment of cerebral ischemia making use of general magnetic therapy.

  2. Ischemia modified albumin as laboratory marker of acute

    Directory of Open Access Journals (Sweden)

    Goran Miličević

    2009-02-01

    Full Text Available Daily clinical practice still lacks a marker of acute myocardial ischemia as compared with markers ofmyocardial necrosis. Ischemia modifed albumin (IMA has recently been proposed as a useful biochemicaltool for detection of ischemia – it is a test which determines the inability of N-terminal end ofalbumin to bind cobalt during ischemia. A strong relation between IMA and early myocardial ischemiahas been shown by several studies, in most of which percutaneous coronary intervention was used asa model of myocardial ischemia, where this test showed high sensitivity. IMA values raise during nextfew minutes after the ischemia has occured, and return back to normal levels within next six hours, butthe precise dynamics of its rise and fall are still unknown. Beside defining etiology of acute or sub-acutechest pain in patients with inconclusive electrocardiogram (ECG, in patients with “silent” myocardialischemia with ischemic changes in ECG or in patients with non-ischemic ECG changes during cardiacstress test, this promising marker could also be used as the earliest biochemical indicator of early developmentof myocardial infarction. Relatively low organ-specificity is a limitation of this test, becauseIMA levels are also raised during different ischemic conditions and diseases of other organs. If thisproblem is taken into consideration, IMA test shows good results in diagnosing myocardial ischemiadue to its high sensitivity.

  3. Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Nirmal

    2007-01-01

    The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysfunction in mice. Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in mice. Short-term memory was evaluated using the elevated plus maze test. The inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced impaired short-term memory, motor co-ordination and lateral push response. Three episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced behavioral deficit measured in terms of loss of short-term memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that beneficial effects of ischemic postconditioning on global cerebral ischemia and reperfusion-induced behavioral deficits may involve activation of phosphoinositide 3-kinase-linked pathway.

  4. Effects of hypoxic preconditioning on the changes of expression of neuroglobin mRNA and labeled positive cells following cerebral ischemia in gerbils

    Institute of Scientific and Technical Information of China (English)

    Yong Zhang; Yanqun Chang; Zhenfang Liu; Qingxi Fu; Xiao Zhang

    2006-01-01

    BACKGROUND: Neuroglobin (NGB), as newly discovered the third member of the globin family binding oxygen, mainly exists in brain of human beings and vertebrates, and it is closely correlated with the oxygen supply in brain.OBJECTIVE : To observe the changes of the expression of neuroglobin and number of positive cells labeled immunohistochemically following cerebral ischemia in gerbils after hypoxic preconditioning. DESIGN: A complete randomized grouping design and controlled experiment. SETTING: Department of Neurology, Department of Anesthesia, Shandong Provincial Hospital, Shandong University.MATERIALS: Sixty-six adult male Mongolian gerbils of clean degree, about 50-65 g, at an average of 57.5 g were provided by the Experimental Animal Center of Capital Medical University [certificate number of animal quality:SCXK(Beijing)2000-0012]. TRNzil (Tianwei Shidai Company, Beijing), polymerase chain reaction (PCR) primers (synthetized by Invitrogen Company, Shanghai); reverse transcription-PCR (RT-PCR) one-step kit (Toyobo Company); PCR instrument (GeneAmp PCR System 240); mice brain NGB monoclonal antibody (Academy of Military Medical Sciences); DAB (Zhongshan Company, Beijing). METHEDS: The study was completed from December 2004 to June 2005 in Shandong Provincial Hospital. ① The 66 gerbils were randomly divided into sham-operated group (n =6), cerebral ischemia group (n =30) and hypoxic preconditioning group (n =30). The gerbils in the hypoxic preconditioning group were put in the environment which contained O2 (0.08 in volume fraction) and N2 (0.92 in volume fraction) at temperature of 25 ℃ for 2 hours. After 5 hours, the gerbils in the hypoxic preconditioning group and cerebral ischemia group were anesthetized, then bilateral common carotid arteries were ligated. In the sham-operated group, bilateral common carotid arteries were only isolated without ligation and hypoxic preconditioning. ②2 At 1, 5, 10, 30 and 60 minutes after cerebral ischemia, the

  5. Basic principles of magnetic resonance imaging in cerebral ischemia and initial clinical experience

    International Nuclear Information System (INIS)

    Brant-Zawadzki, M.; Solomon, M.; Newton, T.H.; Weinstein, P.; Schmidley, J.; Norman, D.

    1985-01-01

    The basic principles of magnetic resonance imaging are described and their use in the investigation of cerebral ischemia outlined. A brief account is given of the clinical results of investigation to date

  6. Impact of Cardiac Contractility during Cerebral Blood Flow in Ischemia

    Directory of Open Access Journals (Sweden)

    Silver, Brian

    2011-05-01

    Full Text Available Objective: In cerebral regions affected by ischemia, intrinsic vascular autoregulation is often lost. Blood flow delivery depends upon cardiac function and may be influenced by neuro-endocrine mediated myocardial suppression. Our objective is to evaluate the relation between ejection fraction (EF and transcranial doppler (TCD peak systolic velocities (PSV in patients with cerebral ischemic events.Methods: We conducted a retrospective cohort study from an existing TCD registry. We evaluated patients admitted within 24 hours of onset of a focal neurological deficit who had an echocardiogram and TCD performed within 72 hours of admission.Results: We identified 58 patients from March to October 2003. Eighty-one percent (n=47 had a hospital discharge diagnosis of ischemic stroke and 18.9% (n=11 had a diagnosis of transient ischemic attack. Fourteen patients had systolic dysfunction (EF50% compared to those with systolic dysfunction (EF<50% was as follows: middle cerebral artery 62.0 + 28.6 cm/s vs. 51.0 + 23.3 cm/s, p=0.11; anterior cerebral artery 52.1 + 21.6 cm/s vs. 45.9 + 22.7 cm/s, p=0.28; internal carotid artery 56.5 + 20.1 cm/s vs. 46.4 + 18.4 cm/s, p=0.04; ophthalmic artery 18.6 + 7.2 cm/s vs. 15.3 + 5.2 cm/s, p=0.11; vertebral artery 34.0 + 13.9 cm/s vs. 31.6 + 15.0 cm/s, p=0.44.Conclusion: Cerebral blood flow in the internal carotid artery territory appears to be higher in cerebral ischemia patients with preserved left ventricular contractility. Our study was unable to differentiate pre-existing cardiac dysfunction from neuro-endocrine mediated myocardial stunning. Future research is necessary to better understand heart-brain interactions in this setting and to further explore the underlying mechanisms and consequences of neuro-endocrine mediated cardiac dysfunction. [West J Emerg Med. 2011;12(2:227-232.

  7. Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia

    Science.gov (United States)

    Deguchi, Kentaro; Liu, Ning; Liu, Wentao; Omote, Yoshio; Kono, Syoichiro; Yunoki, Taijun; Deguchi, Shoko; Yamashita, Toru; Ikeda, Yoshio; Abe, Koji

    2014-01-01

    Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:24938625

  8. MRI of experimental focal cerebral ischemia in sheep

    International Nuclear Information System (INIS)

    Foerschler, A.; Waldmin, D.; Gille, U.; Leipzig Univ.; Zimmer, C.

    2007-01-01

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2 * sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 ± 5.7; 13; 1.7 ± 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  9. Diffusion-weighted magnetic resonance imaging reflects activation of signal transducer and activator of transcription 3 during focal cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Wen-juan Wu

    2017-01-01

    Full Text Available Signal transducer and activator of transcription (STAT is a unique protein family that binds to DNA, coupled with tyrosine phosphorylation signaling pathways, acting as a transcriptional regulator to mediate a variety of biological effects. Cerebral ischemia and reperfusion can activate STATs signaling pathway, but no studies have confirmed whether STAT activation can be verified by diffusion-weighted magnetic resonance imaging (DWI in rats after cerebral ischemia/reperfusion. Here, we established a rat model of focal cerebral ischemia injury using the modified Longa method. DWI revealed hyperintensity in parts of the left hemisphere before reperfusion and a low apparent diffusion coefficient. STAT3 protein expression showed no significant change after reperfusion, but phosphorylated STAT3 expression began to increase after 30 minutes of reperfusion and peaked at 24 hours. Pearson correlation analysis showed that STAT3 activation was correlated positively with the relative apparent diffusion coefficient and negatively with the DWI abnormal signal area. These results indicate that DWI is a reliable representation of the infarct area and reflects STAT phosphorylation in rat brain following focal cerebral ischemia/reperfusion.

  10. Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats.

    Science.gov (United States)

    Ma, Xiao-Hui; Gao, Qiang; Jia, Zhen; Zhang, Ze-Wei

    2015-02-01

    Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway. Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg). TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically. TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

  11. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage

    NARCIS (Netherlands)

    Hijdra, A.; van Gijn, J.; Nagelkerke, N. J.; Vermeulen, M.; van Crevel, H.

    1988-01-01

    Using logistic regression, we analyzed the predictive value of a number of entry variables with respect to the outcome variables delayed cerebral ischemia, rebleeding, and poor outcome (death or severe disability) in patients with aneurysmal subarachnoid hemorrhage. The entry variables were clinical

  12. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia.

    Science.gov (United States)

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L; Neumann, Jake T; Dave, Kunjan R; Perez-Pinzon, Miguel A

    2014-02-01

    We previously showed that palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Solutol HS15, a clinically approved excipient because it possesses similar fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium staining of the brain was performed 24 h after MCAO and the infarct volume was quantified. Following ACA, the number of surviving hippocampal neurons was enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15 (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle) in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS15 is already administered as a solublizing agent to patients. With proper timing and dosage, administration of Solutol HS15 and PAME/SAME can be an effective therapy against cerebral ischemia.

  13. Relationship between blood uric and acute cerebral infarction

    International Nuclear Information System (INIS)

    Yin Zhanxia; Zhao Danyang

    2011-01-01

    Objective: To study the relationship between blood uric acid and acute cerebral infarction. Methods: The level of blood uric acid and prevalence of hyperuricemia (HUA) were compared in 360 patients with acute cerebral infarction and 300 patients without it. According to the level of blood uric acid, 360 acute cerebral infarction patients were divided into HUA and normouricemia (NUA) groups. Age, sex, body mass index (BMI), blood glucose and total cholesterol were compared between the HUA and NUA group. The degree of neurological functional defection was compared between the two groups when patients were attacked by acute cerebral infarction. After a recovery treatment, the neurological functional defection of the two groups was compared a second time. Results: (1)The average blood uric acid level and prevalence of HUA were higher in patients with acute cerebral infarction. (2) The BMI, blood glucose and total cholesterol were higher in HUA group than in NUA group. (3) The neurological functional defection was more serious in HUA group when patients were attacked by acute cerebral infarction and after a recovery treatment. Conclusion: Hyperuricemia is related to acute cerebral infarction. (authors)

  14. Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Zagrean, L; Vatasescu, R; Munteanu, A M

    2000-01-01

    and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF......--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats (p

  15. Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

    Science.gov (United States)

    Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

    2011-06-01

    [¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

  16. [Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

    Science.gov (United States)

    Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

    2017-10-01

    To explore the application value and forensic significance of ischemia modified albumin (IMA) in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group ( n =36), acute myocardial infarction group ( n =6), cardiomyopathy group ( n =4) and control group ( n =15) by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics (ROC) curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group ( P 0.05). The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

  17. Study on diffusion anisotropy of cerebral ischemia using diffusion weighted echo-planar MRI

    International Nuclear Information System (INIS)

    Kajima, Toshio

    1997-01-01

    Focal cerebral ischemia was produced by occlusion of the intracranial main cerebral artery with a silicone cylinder in Wistar rats. Diffusion-weighted echo-planar images (DW-EPls) using the motion-probing gradient (MPG) method were acquired at 1-3 hours and 24-48 hours after occlusion. Apparent diffusion coefficients (ADCs) were calculated from these images in ischemic lesions and in normal unoccluded regions. Results were as follows. Ischemic lesions could be detected on the DW-EPIs at 1 hour after occlusion. The ADC of water in the brain tissue was smaller than that of free water as a result of restricted diffusion. Anisotropic diffusion that probably can be attributed to the myelin sheath was observed in the normal white matter. In the ischemic lesions, the ADC decreased rapidly within 1-3 hours after occlusion and then decreased gradually after 24-48 hours. In the ischemic white matter, diffusion anisotropy disappeared at 24-48 hours after occlusion. Diffusion-weighted imaging may have applications in the examination of pathophysiological mechanisms in cerebral ischemia by means of evaluation of ADC and diffusion anisotropy. (author)

  18. Identification of Reversible Disruption of the Human Blood-Brain Barrier Following Acute Ischemia.

    Science.gov (United States)

    Simpkins, Alexis N; Dias, Christian; Leigh, Richard

    2016-09-01

    Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator. © 2016 American Heart Association, Inc.

  19. [Management of Acute Type A Dissection Complicated with Acute Mesenteric Ischemia].

    Science.gov (United States)

    Abe, Tomonobu; Usui, Akihiko

    2017-07-01

    Acute mesenteric ischemia as malperfusion syndrome associated with acute aortic dissection is a difficult situation. The incidence is approximately 3~4% in acute type A dissection. Traditionally, most of these patients underwent immediate simple central aortic repair expecting that mesenteric artery obstruction and intestinal ischemia would be resolved by simple central aortic repair. However, short term mortality has been reported very high in this strategy. With the aid of rapidly progressing imaging techniques and newer endovascular repair techniques, results seem to be improving in recent years. Newer management strategy include aggressive and patient specific revascularization to the mesenteric arteries, delayed central aortic repair, and meticulous intensive care. Diagnosis and management of this condition require high level of expertise. Cardiac surgeons, vascular surgeons, interventional radiologists, gastroenterologists, general surgeons, anesthesiologists, intensivists must corporate to save these patients' lives. Since this is a relatively rare condition, scientific evidence is insufficient to make robust recommendations. Further studies are warranted.

  20. Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

    Science.gov (United States)

    Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

    2014-08-21

    Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

  1. Statistical modeling of the mother-baby system in newborn infants with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    A. V. Filonenko

    2014-01-01

    Full Text Available The statistical model could consider the influence of specific maternal psychoemotional and personality factors on a newborn with cerebral ischemia and develop a procedure to prevent negative consequences of postpartum depression in the mother-baby system.

  2. Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia. A PET study in rat and canine models of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Hashimoto, Tadatoshi

    2000-01-01

    Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the tricarboxylic acid (TCA) cycle after β-oxidation. We speculate that [1- 11 C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1- 11 C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [ 15 O]H 2 O measured 1-2 h and 5-6 h after insult was compared with that of [1- 11 C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [ 15 O]H 2 O were lower than those determined with [1- 11 C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1- 11 C]octanoate was observed in the ischemic regions. The uptake of [1- 11 C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1- 11 C]octanoate provides functional information different from CBF. In conclusion, we found that [1- 11 C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. (author)

  3. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

    Science.gov (United States)

    Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

    2004-09-15

    Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

  4. Diagnosis of acute ischemia using dual energy CT after mechanical thrombectomy.

    Science.gov (United States)

    Gariani, Joanna; Cuvinciuc, Victor; Courvoisier, Delphine; Krauss, Bernhard; Mendes Pereira, Vitor; Sztajzel, Roman; Lovblad, Karl-Olof; Vargas, Maria Isabel

    2016-10-01

    To assess the performance of dual energy unenhanced CT in the detection of acute ischemia after mechanical thrombectomy. Retrospective study, approved by the local institutional review board, including all patients that underwent intra-arterial thrombectomy in our institution over a period of 2 years. The presence of acute ischemia and hemorrhage was evaluated by three readers. Sensitivity and specificity of the non-contrast CT weighted sum image (NCCT) and the virtual non-contrast reconstructed image (VNC) were estimated and compared using generalized estimating equations to account for the non-independence of regions in each patient. 58 patients (27 women and 31 men; mean age 70.4 years) were included in the study, yielding 580 regions of interest. Sensitivity and specificity in detecting acute ischemia were higher for all readers when using VNC, with a significant increase in sensitivity for two readers (pVNC images were superior in the identification of acute ischemia in comparison with NCCT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Cerebral blood flow in cerebral ischemia. A review (with 1 color plate)

    DEFF Research Database (Denmark)

    Lassen, N A

    1978-01-01

    In the majority of apoplexy patients the absence of a primary haemorrhage points to acute vascular occclusion with regional ischemia as the initiating event. Yet, in many such cases in particular with transient symptoms, no occlusions can be found angiographically. This along with other evidences...... and of metabolic integrity of tissue areas be possible as a prerequisite for rational therapy....

  6. Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion

    Directory of Open Access Journals (Sweden)

    Lei Ruan

    2017-01-01

    Full Text Available Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions (such as the contralateral cerebral hemisphere. The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis (shown by the increase in lactate, a perturbation of choline metabolism (suggested by the increase in choline, neuronal cell damage (shown by the decrease in N-acetyl aspartate and neurotransmitter imbalance (evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a

  7. Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

    Directory of Open Access Journals (Sweden)

    Le Li

    2016-01-01

    Full Text Available Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response. As endogenous miR expression patterns can be altered with exogenous mimics and inhibitors, miR-targeted therapies represent a viable intervention to optimize glial mitochondrial function and improve clinical outcome following cerebral ischemia. In the present article, we review the role that astrocytes and microglia play in neuronal function and fate following ischemic stress, discuss the relevance of mitochondria in the glial response to injury, and present current evidence implicating miRs as critical regulators in the glial mitochondrial response to cerebral ischemia.

  8. Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

    Science.gov (United States)

    Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

    2014-01-01

    Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p exogenous Ngb. PMID:24966924

  9. Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke

    DEFF Research Database (Denmark)

    Lassen, N A

    1990-01-01

    Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also...

  10. Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Bing Zhao

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

  11. Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jianjun Zhao; Yong Liu; Xinlin Chen; Jianxin Liu; Yingfang Tian; Pengbo Zhang; Qianyan Kang; Fen Qiu

    2006-01-01

    BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation.OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial.SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University.MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co. Ltd (Lot Number: 2004051106, Specification: 2 mL/piece).METHODS: The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, Iow-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections.MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed,RESULTS : Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the

  12. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  13. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    International Nuclear Information System (INIS)

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca"2"+ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  14. High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

    Science.gov (United States)

    Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

    2013-09-13

    Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

    Science.gov (United States)

    Durmaz, Ramazan; Ozden, Hilmi; Kanbak, Güngör; Aral, Erinç; Arslan, Okan Can; Kartkaya, Kazim; Uzuner, Kubilay

    2008-09-01

    We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p agent for the treatment of stroke patients.

  16. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Østergaard, Kamilla; Clausen, Bettina Hjelm

    2014-01-01

    known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. METHODS: The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory...... and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry......-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected...

  17. Chinese herbal formula Tongluo Jiunao injection protects against cerebral ischemia by activating neurotrophin 3/tropomyosin-related kinase C pathway

    Directory of Open Access Journals (Sweden)

    Peiman Alesheikh

    2015-01-01

    Full Text Available The Chinese herbal formula Tongluo Jiunao, containing the active components Panax notoginseng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control (Xuesai Tong, containing Panax notoginseng or saline intraperitoneally to investigate the pathway involved in the action of Tongluo Jiunao injection. 2,3,5-Triphenyltetrazolium chloride (TTC staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo Jiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo Jiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/tropomyosin-related kinase C pathway.

  18. Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice

    Directory of Open Access Journals (Sweden)

    Qiusheng Zheng

    2012-08-01

    Full Text Available The air-dried aerial parts of Lavandula angustifolia Mill, a traditional Uygur herbal drug, is used as resuscitation-inducing therapy to treat neurodisfunctions, such as stroke. This study was designed to assess the neuroprotective effects of lavender oil against ischemia/reperfusion (IR injury in mice. Focal cerebral ischemia was induced by the intraluminal occlusion method with a nylon string. The neurodysfuntion was evaluated by neurological deficit and the infarct area was showed by 2,3,5-triphenyltetrazolium chloride (TTC staining. The histopathological changes were observed by hematoxylin and eosin staining. The levels of mitochondria-generated reactive oxygen species (ROS, malondialdehyde (MDA and carbonyl, the ratio of reduced glutathione (GSH/glutathione disulfide (GSSG, the activities of superoxide dismutase (SOD, catalase (CAT and glutathion peroxidase (GSH-Px in brain tissue were measured to estimate the oxidative stress state. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22 h of reperfusion. In comparison with the model group, treatment with lavender oil significantly decreased neurological deficit scores, infarct size, the levels of MDA, carbonyl and ROS, and attenuated neuronal damage, upregulated SOD, CAT, GSH-Px activities and GSH/GSSG ratio. These results suggested that the neuroprotective effects of lavender oil against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.

  19. Acute coronary ischemia during alcohol withdrawal: a case report

    Directory of Open Access Journals (Sweden)

    Sriram Ganeshalingam

    2011-08-01

    Full Text Available Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

  20. Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : the role of coagulation and fibrinolysis

    NARCIS (Netherlands)

    Vergouwen, M.D.I.

    2009-01-01

    Patients with aneurysmal subarachnoid hemorrhage (SAH) are at risk to develop complications, especially within the first two weeks after the hemorrhage. Delayed cerebral ischemia (DCI) is a complication which occurs in about 30% of SAH patients, leading to symptoms such as aphasia, hemiparesis, or

  1. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia.

    Science.gov (United States)

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M; McCullough, Louise; Andreasson, Katrin

    2008-06-20

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

  2. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Li LIU

    2013-03-01

    Full Text Available Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results  Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions  Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

  3. [Effects of combined use of total alkaloids of Uncaria rhynchophylla and Coryadlis ambailis migo on cerebral ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Hu, Xue-yong; Sun, An-sheng; Sui, Yu-xia

    2007-11-01

    To study the effects of combined use of total alkaloids (TA) of Uncaria rhynchophylla (UR) and Coryadlis ambailis migo (CAM) on cerebral ischemia/reperfusion injury in rats. Rat model of middle cerebral artery ischemia/reperfusion was established, the changes of neurological state was scored before and after treatment with the two kinds of TA, single or combined, and the changes of cerebral infarcted volume, cerebral water content, activities of NOS and SOD and content of MDA in rats' brain were estimated as well. After being treated with the combination of both TA, the average neurological score, cerebral infracted volume, cerebral water content, activity of NOS and content of MDA in the model rats significantly decreased, and the activity of SOD was significantly increased (all P < 0.05). The effect of combined use of the two TA was higher than that of use TA of UR or CAM alone (P <0.05). Moreover, the central nervous system inhibitory effect induced by combined TA was significantly weaker than that of UR. Combined use of TA of UR and CAM may facilitate the protection against cerebral ischemia/reperfusion damage, the action mechanism might be relevant to reducing the lipid peroxidation injury of brain cells through inhibiting the NOS activity and increasing the SOD activity.

  4. Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Han, Jin; Wan, Hai-Tong; Yang, Jie-Hong; Zhang, Yu-Yan; Ge, Li-Jun; Bie, Xiao-Dong

    2014-01-01

    This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.

  5. Contribution of positron emission tomography to physiopathological study of cerebral ischemia in man

    Energy Technology Data Exchange (ETDEWEB)

    Baron, J C; Bousser, M G; Comar, D; Rougemont, D; Lebrun-Grandie, P [Commissariat a l' Energie Atomique, Centre Hospitalier Frederic Joliot, 91 - Orsay (France); Castaigne, P [Hopital de la Salpetriere, 75 - Paris (France)

    1983-12-29

    The development of positron emission tomography now allows the local study of cerebral blood flow, oxygen consumption and glucose utilization in ischemic stroke patients. In recent cerebral infarction, a disruption of the normal couple between flow and metabolism is almost constantly observed: in the first few days cerebral blood flow is either inadequate (persistant ischemia) or over-abundant (''luxury perfusion''), whereas a late ''luxury perfusion'' is almost constant within the necrotic area between the 10th and the 40th day. Threshold values for cerebral blood flow and oxygen consumption that are ultimately associated with necrosis or tissue integrity have been determined. A metabolic depression without C.T. Scan counterpart has been observed in various brain structures remote from the infarcted area per se. Lastly, the hemodynamic and metabolic effects of superficial-temporal-middle-cerebral-artery anastomosis have been studied.

  6. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage: a substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II).

    Science.gov (United States)

    Leijenaar, Jolien F; Dorhout Mees, Sanne M; Algra, Ale; van den Bergh, Walter M; Rinkel, Gabriel J E

    2015-10-01

    Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia. We investigated if magnesium treatment led to less delayed cerebral ischemia and if glucose levels interacted with magnesium treatment in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. To investigate the effect of magnesium treatment on occurrence of delayed cerebral ischemia and the interaction between glucose levels and magnesium treatment in subarachnoid hemorrhage patients. The Magnesium in Aneurysmal Subarachnoid Haemorrhage was a phase III randomized placebo-controlled trial assessing the effect of magnesium sulphate on clinical outcome in aneurysmal subarachnoid hemorrhage patients. For the current study, we included only the patients admitted to the University Medical Centre-Utrecht. We calculated hazard ratios for occurrence of delayed cerebral ischemia in patients treated with magnesium vs. placebo for the entire study population, and separately in the subgroups of patients with high and low mean fasting and mean daily glucose levels until onset of delayed cerebral ischemia. We used the cross-product of magnesium and glucose in the regression analysis to evaluate whether an interaction between magnesium and glucose existed. We included 616 patients: 307 received magnesium and 309 placebo; 156 patients had delayed cerebral ischemia. Hazard ratio for magnesium on occurrence of delayed cerebral ischemia was 1·0 (95% confidence interval: 0·7-1·4). Results were similar in patients with low or high fasting or daily glucose levels. We found no interactions between magnesium treatment and high fasting (P = 0·54) and daily glucose (P = 0·60). Magnesium treatment did not reduce the risk of delayed cerebral ischemia in patients with aneurysmal

  7. Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

    International Nuclear Information System (INIS)

    Wagner, Marlies; Kyriakou, Yiannis; Mesnil de Rochemont, Richard du; Singer, Oliver C.; Berkefeld, Joachim

    2013-01-01

    PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy

  8. Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2014-12-01

    Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P piroxicam administration in stroke rat significantly reduced (P piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

  9. Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy.

    Science.gov (United States)

    Vasquez-Vivar, Jeannette; Shi, Zhongjie; Luo, Kehuan; Thirugnanam, Karthikeyan; Tan, Sidhartha

    2017-10-01

    Antenatal brain hypoxia-ischemia, which occurs in cerebral palsy, is considered a significant cause of motor impairments in children. The mechanisms by which antenatal hypoxia-ischemia causes brain injury and motor deficits still need to be elucidated. Tetrahydrobiopterin is an important enzyme cofactor that is necessary to produce neurotransmitters and to maintain the redox status of the brain. A genetic deficiency of this cofactor from mutations of biosynthetic or recycling enzymes is a well-recognized factor in the development of childhood neurological disorders characterized by motor impairments, developmental delay, and encephalopathy. Experimental hypoxia-ischemia causes a decline in the availability of tetrahydrobiopterin in the immature brain. This decline coincides with the loss of brain function, suggesting this occurrence contributes to neuronal dysfunction and motor impairments. One possible mechanism linking tetrahydrobiopterin deficiency, hypoxia-ischemia, and neuronal injury is oxidative injury. Evidence of the central role of the developmental biology of tetrahydrobiopterin in response to hypoxic ischemic brain injury, especially the development of motor deficits, is discussed. Copyright © 2017. Published by Elsevier B.V.

  10. The Olson method for detection of acute myocardial ischemia in patients with coronary occlusion.

    Science.gov (United States)

    Lindow, Thomas; Olson, Charles W; Swenne, Cees A; Man, Sumche; Pahlm, Olle

    An automated ECG-based method may provide diagnostic support in the management of patients with acute coronary syndrome. The Olson method has previously proved to accurately identify the culprit artery in patients with acute coronary occlusion. The Olson method was applied to 360 patients without acute myocardial ischemia and 52 patients with acute coronary occlusion. This study establishes the normal variation of the Olson wall scores in patients without acute myocardial ischemia, which provides the basis for implementation of the Olson method for triage of patients with acute coronary syndrome. All patients with acute occlusion had Olson wall scores above the upper limit of normal. The Olson method can be used for ischemia detection with very high sensitivity. Future studies are needed to explore specificity in patients with non-ischemic ST elevation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    2001-01-01

    Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. (3)H-D-aspartate (test substance), and (14)C-mannitol (reference substance), were...

  12. The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

    International Nuclear Information System (INIS)

    Xian, Wenjing; Wu, Yan; Xiong, Wei; Li, Longyan; Li, Tong; Pan, Shangwen; Song, Limin; Hu, Lisha; Pei, Lei; Yao, Shanglong

    2016-01-01

    Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

  13. The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Xian, Wenjing [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wu, Yan [Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiong, Wei [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Longyan [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Tong [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pan, Shangwen [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Song, Limin [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Hu, Lisha [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pei, Lei [Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yao, Shanglong, E-mail: ysltian@163.com [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); and others

    2016-03-25

    Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

  14. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  15. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

    Science.gov (United States)

    Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

    2009-03-01

    Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

  16. Edaravone, a Free Radical Scavenger, Mitigates Both Gray and White Matter Damages after Global Cerebral Ischemia in Rats

    Science.gov (United States)

    Kubo, Kozue; Nakao, Shinichi; Jomura, Sachiko; Sakamoto, Sachiyo; Miyamoto, Etsuko; Xu, Yan; Tomimoto, Hidekazu; Inada, Takefumi; Shingu, Koh

    2012-01-01

    Recent studies have shown that similar to cerebral gray matter (mainly composed of neuronal perikarya), white matter (composed of axons and glias) is vulnerable to ischemia. Edaravone, a free radical scavenger, has neuroprotective effects against focal cerebral ischemia even in humans. In this study, we investigated the time course and the severity of both gray and white matter damage following global cerebral ischemia by cardiac arrest, and examined whether edaravone protected the gray and the white matter. Male Sprague-Dawley rats were used. Global cerebral ischemia was induced by 5 minutes of cardiac arrest and resuscitation (CAR). Edaravone, 3 mg/kg, was administered intravenously either immediately or 60 minutes after CAR. The morphological damage was assessed by cresyl violet staining. The microtubule-associated protein 2 (a maker of neuronal perikarya and dendrites), the β amyloid precursor protein (the accumulation of which is a maker of axonal damage), and the ionized calcium binding adaptor molecule 1 (a marker of microglia) were stained for immunohistochemical analysis. Significant neuronal perikaryal damage and marked microglial activation were observed in the hippocampal CA1 region with little axonal damage one week after CAR. Two weeks after CAR, the perikaryal damage and microglial activation were unchanged, but obvious axonal damage occurred. Administration of edaravone 60 minutes after CAR significantly mitigated the perikaryal damage, the axonal damage, and the microglial activation. Our results show that axonal damage develops slower than perikaryal damage and that edaravone can protect both gray and white matter after CAR in rats. PMID:19410562

  17. Magnetic resonance imaging in acute ischemic stroke

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    Ohta, Kouichi [Mito Red Cross Hospital (Japan)

    2000-01-01

    This paper summarizes current MRI technology used in the diagnosis of acute cerebral infarction and discusses tasks for further improvement of MRI technology. First, the principles and methods of MRI imaging are described in terms of 1) diffusion-weighted imaging (DWI) and ADC maps, 2) perfusion imaging, 3) the fluid-attenuated inversion recovery (FLAIR) method, and 4) MR angiography (MRA). Then, the actual use of MRI in the early phase of ischemic cerebrovascular disorders is discussed focusing on general MRI procedures, cases in which an ischemic lesion dose not yield a high signal with DWI in the acute phase, and chronological changes in DWI signal strength and ADC. Third, chronological changes in acute cerebrovascular disorder in an animal model of local cerebral ischemia are summarized in terms of expansion of reduced ADC areas and ischemic penumbras in the acute phase of cerebral ischemia. Finally, chronological changes in acute ischemic disorders in patients with cerebrovascular disorders are assessed by reviewing the development of reduced ADC and expansion of DWI lesions. Whether MRI can identify cerebral tissues that can be rescued by the reperfusion method by examining the mismatchs between perfusion images and DWI, relative CBV, and ADC is also discussed. (K.H.)

  18. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

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    Nietfeld Wilfried

    2010-03-01

    Full Text Available Abstract Background The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC and its inhibitor-protein CD59. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death. Results and Discussion CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO. Conclusion We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

  19. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Zhao, Jing; Zhao, Yong; Zheng, Weiping; Lu, Yuyu; Feng, Gang; Yu, Shanshan

    2008-09-10

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

  20. Endovascular Management of Acute Limb Ischemia.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2011-09-14

    Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series. This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies.

  1. Anchusa italica extract: phytochemical and neuroprotective evaluation on global cerebral ischemia and reperfusion

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    Akram Torki

    2018-06-01

    Full Text Available Abstract Stroke is the third leading cause of mortality and disability in industrial countries. Treatment with herbs with antioxidant properties has been reported to be an alternative to the conventional treatments. This study was conducted to investigate the effect of Anchusa italica extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in the rat. To do so, 50 rats were randomly assigned to five groups; control, sham, ischemia, and 50 or 100 mg/kg of Anchusa italica treated animals. Ischemia was induced by occlusion of carotid artery for 30 minutes. Afterward, behavioral tests and biochemical analyses were conducted. Induction of ischemia/reperfusion caused a decline in learning and passive avoidance memory in rats. Moreover, Anchusa italica caused an increase in learning and improved the passive avoidance memory. Induction of ischemia/reperfusion caused a decrease in the antioxidant capacity of the brain and serum as well as an increase in the malondialdehyde of the brain and serum. Anchusa italica led to an increase in the antioxidant capacity of the brain and serum and decrease in the malondialdehyde of the brain and serum. Overall, because of its protective effects on spatial memory, passive avoidance learning, antioxidant capacity, and lipid peroxidation during ischemia/reperfusion, Anchusa italica might be beneficial in ischemic patients.

  2. Cerebral hypoxia and ischemia in preterm infants

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    Alberto Ravarino

    2014-06-01

    Full Text Available Premature birth is a major public health issue internationally affecting 13 million babies worldwide. Hypoxia and ischemia is probably the commonest type of acquired brain damage in preterm infants. The clinical manifestations of hypoxic-ischemic injury in survivors of premature birth include a spectrum of cerebral palsy and intellectual disabilities. Until recently, the extensive brain abnormalities in preterm neonates appeared to be related mostly to destructive processes that lead to substantial deletion of neurons, axons, and glia from necrotic lesions in the developing brain. Advances in neonatal care coincide with a growing body of evidence that the preterm gray and white matter frequently sustain less severe insults, where tissue destruction is the minor component. Periventricular leukomalacia (PVL is the major form of white matter injury and consists classically of focal necrotic lesions, with subsequent cyst formation, and a less severe but more diffuse injury to cerebral white mater, with prominent astrogliosis and microgliosis but without overt necrosis. With PVL a concomitant injury occurs to subplate neurons, located in the subcortical white matter. Severe hypoxic-ischemic insults that trigger significant white matter necrosis are accompanied by neuronal degeneration in cerebral gray and white matter. This review aims to illustrate signs of cerebral embryology of the second half of fetal life and correlate hypoxic-ischemic brain injury in the premature infant. This should help us better understand the symptoms early and late and facilitate new therapeutic strategies. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  3. Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury.

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    Rachel G Khadaroo

    Full Text Available Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis. The objective of this investigation is to use nuclear magnetic resonance (NMR analysis to characterize urine metabolomic profile of AII/R injury in a mouse model. Animals were exposed to sham, early (30 min or late (60 min acute intestinal ischemia by complete occlusion of the superior mesenteric artery, followed by 2 hrs of reperfusion. Urine was collected and analyzed by NMR spectroscopy. Urinary metabolite concentrations demonstrated that different profiles could be delineated based on the duration of the intestinal ischemia. Metabolites such as allantoin, creatinine, proline, and methylamine could be predictive of AII/R injury. Lactate, currently used for clinical diagnosis, was found not to significantly contribute to the classification model for either early or late ischemia. This study demonstrates that patterns of changes in urinary metabolites are effective at distinguishing AII/R progression in an animal model. This is a proof-of-concept study to further support examination of metabolites in the clinical diagnosis of intestinal ischemia reperfusion injury in patients. The discovery of a fingerprint metabolite profile of AII/R will be a major advancement in the diagnosis, treatment, and prevention of systemic injury in critically ill patients.

  4. Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia

    International Nuclear Information System (INIS)

    Kuroda, Satoshi; Sakuragi, Mitsugi; Motomiya, Mineo; Nakagawa, Tango; Mitsumori, Kenji; Tsuru, Mitsuo; Takigawa, Shugo; Kamiyama, Hiroyasu; Abe, Hiroshi.

    1990-01-01

    To evaluate the efficacy of tests for selecting patients with hemodynamic compromise, measurement of cerebral blood volume (CBV) with 99m Tc-RBC single photon emission computed tomography (SPECT) was performed in thirteen patients with occlusive cerebrovascular disease, and was compared with results obtained by 133 Xe SPECT and acetazolamide (Diamox) test. All patients in our study suffered TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery, although plain CT scan or MRI revealed no or, if any, only localized infarcted lesions. Regional cerebral blood volume (rCBV) was measured with 99m Tc-RBC SPECT and regional cerebral blood flow (rCBF) was measured with 133 Xe SPECT before and after intravenous injection of 10 - 12 mg/kg acetazolamide (Diamox). Our results suggest that the ipsilateral rCBV/rCBF (mean transit time) is a more sensitive index of the cerebral perfusion reserve than the use of only rCBV or rCBF of the ipsilateral hemisphere. Also, the ipsilateral rCBV/rCBF is significantly correlated (r= -0.72) with the Diamox reactivity of rCBF, which is considered to represent the cerebral vasodilatory capacity in patients with chronic cerebral ischemia. Postoperative SPECT study revealed remarkable improvement of ipsilateral rCBV/rCBF and Diamox reactivity in four patients who underwent EC/IC bypass surgery to improve the hemodynamic compromise. In conclusion, our results suggest that the measurement of rCBV/rCBF with 133 Xe SPECT and 99m Tc-RBC SPECT is useful for detecting the hemodynamic compromise in patients with occlusive cerebrovascular disease. (author)

  5. Niosomes of ascorbic acid and α-tocopherol in the cerebral ischemia-reperfusion model in male rats.

    Science.gov (United States)

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4-8(°)C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  6. Cerebral Vasospasm with Ischemia following a Spontaneous Spinal Subarachnoid Hemorrhage

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    Sophia F. Shakur

    2013-01-01

    Full Text Available Cerebral vasospasm is a well-known consequence of aneurysmal subarachnoid hemorrhage (SAH triggered by blood breakdown products. Here, we present the first case of cerebral vasospasm with ischemia following a spontaneous spinal SAH. A 67-year-old woman, who was on Coumadin for atrial fibrillation, presented with chest pain radiating to the back accompanied by headache and leg paresthesias. The international normalized ratio (INR was 4.5. Ten hours after presentation, she developed loss of movement in both legs and lack of sensation below the umbilicus. Spine MRI showed intradural hemorrhage. Her coagulopathy was reversed, and she underwent T2 to T12 laminectomies. A large subarachnoid hematoma was evacuated. Given her complaint of headache preoperatively and the intraoperative finding of spinal SAH, a head CT was done postoperatively that displayed SAH in peripheral sulci. On postoperative day 5, she became obtunded. Brain MRI demonstrated focal restricted diffusion in the left frontoparietal area. Formal angiography revealed vasospasm in anterior cerebral arteries bilaterally and right middle cerebral artery. Vasospasm was treated, and she returned to baseline within 48 hours. Spontaneous spinal SAH can result in the same sequelae typically associated with aneurysmal SAH, and the clinician must have a degree of suspicion in such patients. The pathophysiological mechanisms underlying cerebral vasospasm may explain this unique case.

  7. Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia

    International Nuclear Information System (INIS)

    Frechou, M.; Beray-Berthat, V.; Plotkine, M.; Marchand-Leroux, C.; Margaill, I.; Raynaud, J.S.; Gombert, F.; Lancelot, E.; Ballet, S.; Robert, P.; Louin, G.; Meriaux, S.

    2013-01-01

    Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nano-particular contrast agent P03011, an USPIO (ultra-small superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or non-targeted USPIO P03007 were injected 5 h after ischemia (100 mmol iron kg -1 ; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. (authors)

  8. Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

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    Erol-Demirbilek Melike

    2016-09-01

    Full Text Available Background: Thioredoxin reductase (TrxR, epidermal growth factor (EGF and tumor necrosis factor-α (TNF-α have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

  9. Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances neurogenesis in the subgranular zone of dentate gyrus after transient global cerebral ischemia in rats.

    Science.gov (United States)

    Lei, Shan; Zhang, Pengbo; Li, Weisong; Gao, Ming; He, Xijing; Zheng, Juan; Li, Xu; Wang, Xiao; Wang, Ning; Zhang, Junfeng; Qi, Cunfang; Lu, Haixia; Chen, Xinlin; Liu, Yong

    2014-01-01

    Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p edaravone also decreased apoptosis of NSPCs (p edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Pre- and Posttreatment With Edaravone Protects CA1 Hippocampus and Enhances Neurogenesis in the Subgranular Zone of Dentate Gyrus After Transient Global Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Shan Lei

    2014-11-01

    Full Text Available Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15, control (n = 15, and edaravone-treated (n = 15 groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05. Treatment with edaravone also decreased apoptosis of NSPCs (p < .01. Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia.

  11. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

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    Vasilenko Т.М.

    2015-09-01

    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  12. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

  13. Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

    Science.gov (United States)

    Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

    2017-01-01

    Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

  14. Acute mesenteric ischemia: a vascular emergency.

    Science.gov (United States)

    Klar, Ernst; Rahmanian, Parwis B; Bücker, Arno; Hauenstein, Karlheinz; Jauch, Karl-Walter; Luther, Bernd

    2012-04-01

    Acute mesenteric ischemia is still fatal in 50% to 70% of cases. This consensus paper was written with the participation of physicians from all of the involved specialties for the purpose of improving outcomes. Mesenteric ischemia must be recognized as a vascular emergency requiring rapid and efficient clinical evaluation and treatment. We reviewed pertinent literature that was retrieved by a PubMed search on the terms "mesenteric ischemia" AND "arterial" OR "venous" OR "clinical presentation" OR "diagnosis" OR "therapy" OR "surgery" OR " interventional radiology." Our review also took account of the existing guidelines of the American College of Cardiology/American Heart Association. Intensive discussions among the participating physicians, representing all of the specialties involved in the management of mesenteric ischemia, led to the creation of this interdisciplinary paper. Biphasic contrast-enhanced computerized tomography is the diagnostic tool of choice for the detection of arterial or venous occlusion. If non-occlusive mesenteric ischemia is suspected, angiography should be performed, with the option of intraarterial pharmacotherapy to induce local vasodilation. Endovascular techniques have become increasingly important in the treatment of arterial occlusion. Embolic central mesenteric artery occlusion requires surgical treatment; surgery is also needed in case of peritonitis. Portal-vein thrombosis can be treated by local thrombolysis through a transhepatically placed catheter. This should be done within 3 to 4 weeks of the event to prevent later complications of portal hypertension. Rapid diagnosis (within 4 to 6 hours of symptom onset) and interdisciplinary cooperation in the provision of treatment are required if the poor outcome of this condition is to be improved.

  15. Optimized Model of Cerebral Ischemia In situ for the Long-Lasting Assessment of Hippocampal Cell Death

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    Oksana Rybachuk

    2017-07-01

    Full Text Available Among all the brain, the hippocampus is the most susceptible region to ischemic lesion, with the highest vulnerability of CA1 pyramidal neurons to ischemic damage. This damage may cause either prompt neuronal death (within hours or with a delayed appearance (over days, providing a window for applying potential therapies to reduce or prevent ischemic impairments. However, the time course when ischemic damage turns to neuronal death strictly depends on experimental modeling of cerebral ischemia and, up to now, studies were predominantly focused on a short time-window—from hours to up to a few days post-lesion. Using different schemes of oxygen-glucose deprivation (OGD, the conditions taking place upon cerebral ischemia, we optimized a model of mimicking ischemic conditions in organotypical hippocampal slices for the long-lasting assessment of CA1 neuronal death (at least 3 weeks. By combining morphology and electrophysiology, we show that prolonged (30-min duration OGD results in a massive neuronal death and overwhelmed astrogliosis within a week post-OGD whereas OGD of a shorter duration (10-min triggered programmed CA1 neuronal death with a significant delay—within 2 weeks—accompanied with drastically impaired CA1 neuron functions. Our results provide a rationale toward optimized modeling of cerebral ischemia for reliable examination of potential treatments for brain neuroprotection, neuro-regeneration, or testing neuroprotective compounds in situ.

  16. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  17. Transesophageal echocardiography in patients with cryptogenic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dreger Henryk

    2009-03-01

    Full Text Available Abstract Background In about one third of all patients with cerebral ischemia, no definite cause can be identified (cryptogenic stroke. In many patients with initially suspected cryptogenic stroke, however, a cardiogenic etiology can eventually be determined. Hence, the aim of this study was to describe the prevalence of abnormal echocardiographic findings in a large number of these patients. Method Patients with cryptogenic cerebral ischemia (ischemic stroke, IS, and transient ischemic attack, TIA were included. The initial work-up included a neurological examination, EEG, cCT, cMRT, 12-lead ECG, Holter-ECG, Doppler ultrasound of the extracranial arteries, and transthoracic echocardiography. A multiplane transeophageal echocardiography (TEE, including i.v. contrast medium application [Echovist], Valsalva maneuver was performed in all patients Results 702 consecutive patients (380 male, 383 IS, 319 TIA, age 18–90 years were included. In 52.6% of all patients, TEE examination revealed relevant findings. Overall, the most common findings in all patients were: patent foramen ovale (21.7%, previously undiagnosed valvular disease (15.8%, aortic plaques, aortic valve sclerosis, atrial septal aneurysms, regional myocardial dyskinesia, dilated left atrium and atrial septal defects. Older patients (> 55 years, n = 291 and patients with IS had more relevant echocardiographic findings than younger patients or patients with TIA, respectively (p = 0.002, p = 0.003. The prevalence rates of PFO or ASD were higher in younger patients (PFO: 26.8% vs. 18.0%, p = 0.005, ASD: 9.6% vs. 4.9%, p = 0.014. Conclusion A TEE examination in cryptogenic stroke reveals contributing cardiogenic factors in about half of all patients. Younger patients had a higher prevalence of PFO, whereas older patients had more frequently atherosclerotic findings. Therefore, TEE examinations seem indicated in all patients with cryptogenic stroke – irrespective of age – because of

  18. Effects of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats

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    Mingsan Miao

    2017-05-01

    Full Text Available The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA, and then expose external carotid artery (ECA and internal carotid artery (ICA. The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire. Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P < 0.05, P < 0.01; and reduce the serum S-100β protein content. Each dose group of the Rabdosia rubescens total flavonoids has a better Improvement effect on focal cerebral ischemia reperfusion model in rats.

  19. Reduced PBR/TSPO Expression After Minocycline Treatment in a Rat Model of Focal Cerebral Ischemia: A PET Study Using [18F]DPA-714

    International Nuclear Information System (INIS)

    Martin, A.; Boisgard, R.; Tavitian, B.; Kassiou, M.; Dolle, F.

    2011-01-01

    Background: Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [ 18 F]DPA-714. Purpose: Here, we tested whether PET with [ 18 F]DPA-714 would evidence the effect of minocycline, a broad spectrum antibiotic presently tested as neuro-protective agent after stroke, on the inflammatory reaction induced in an experimental model of stroke. Procedures: Ten rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. Minocycline or saline was intravenously administrated 1 h after reperfusion and daily during the following 6 days. PET studies were performed using [ 18 F]DPA-714 at 7 days after cerebral ischemia. Results: In vivo PET imaging showed a significant decrease in [ 18 F]DPA-714 uptake at 7 days after cerebral ischemia in rats treated with minocycline with respect to saline-treated animals. Minocycline treatment had no effect on the size of the infarcted area. Conclusion: Minocycline administered daily during 7 days after ischemia decreases [ 18 F]DPA- 714 binding, suggesting that the drug exerts an anti-inflammatory activity. [ 18 F]DPA-714 PET is a useful bio-marker to study novel anti-inflammatory strategies in experimental cerebral ischemia. (authors)

  20. Preliminary experience on early mechanical recanalization of middle cerebral artery for acute ischemic stroke and literature review

    International Nuclear Information System (INIS)

    Bai Weixing; Li Tianxiao; Zhu Liangfu; Xue Jiangyu; Wang Ziliang

    2012-01-01

    Objective: To evaluate the feasibility,efficacy and complication of early middle cerebral artery (MCA) mechanical recanalization (MER) for treatment of acute ischemic stroke. Methods: Seven cases undergone MER of MCA for the treatment of acute cerebral infarct were retrospectively reviewed and analyzed, including the etiology, mechanism, Qureshi grading scale, location and size of infarcts, NIHSS score of pre and post procedure, endovascular technique and complications. Referring to the literature, the indications of MCA recanalization were further identified. Results: A total of 7 cases with mean age of 48 yrs were reviewed, which included 3 cases of atherosclerotic thrombosis and 4 embolic cases with pre NIHSS score ranging from 3 to 22. Mechanical recanalization succeeded in 6 cases, but 2 cases of cardiogenic embolism died of intracranial hemorrhage postoperatively. Favorable clinical outcomes were achieved in 4 cases whereas 1 deteriorated. Overall complications seemed to be consistent with literatures reviewed. Conclusions: Early MER of MCA may benefit to a certain subset of acute ischemia stroke patients, however, embolic cases, elder patients and those with severe neurologic deficits are often accompanied by higher complications and unfavorable outcome. (authors)

  1. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  2. Effect of electroacupuncture on TRPM7 mRNA expression after cerebral ischemia/reperfusion in rats via TrkA pathway.

    Science.gov (United States)

    Zhao, Li; Shi, Jing; Sun, Ning; Tian, Shunlian; Meng, Xianfang; Liu, Xiaochun; Li, Lingli

    2005-01-01

    The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (PPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

  3. Protective Mechanism of STAT3-siRNA on Cerebral Ischemia Injury

    Science.gov (United States)

    He, Jinting; Yang, Le; Liang, Wenzhao

    2018-01-01

    Nerve cells in ischemic brain injury will occur a series of complex signal transduction pathway changes and produce the corresponding biological function, thus affecting the central nervous system functionally different cells in the ischemic brain injury metabolism, division, Differentiation and death process, while changes in signal pathways also play an important role in the repair process of the post-ischemic nervous system. JAK/STAT pathway and vascular lesions have some relevance, but its exact mechanism after cerebral ischemia is not yet fully understood. This study is intended to further explore the JAK / STAT pathway in the functional site of STAT3 in neuronal ischemia Hypoxic injury and related molecular mechanisms, targeting these targets design intervention strategies to block the signal pathway, in order to provide a theoretical basis for the treatment of ischemic brain damage in this pathway.

  4. Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage.

    Science.gov (United States)

    Mutoh, Tomoko; Mutoh, Tatsushi; Sasaki, Kazumasu; Nakamura, Kazuhiro; Tatewaki, Yasuko; Ishikawa, Tatsuya; Taki, Yasuyuki

    2017-02-15

    Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH. Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively. Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (Pprotective agent against EBI. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Abdominal Aortic Dissection with Acute Mesenteric Ischemia in a Patient with Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    Chii-Shyan Lay

    2006-07-01

    Full Text Available Marfan syndrome is an autosomal dominant inherited disorder of connective tissue, with various complications manifested primarily in the cardiovascular system. It potentially leads to aortic dissection and rupture, these being the major causes of death. We report a patient who complained of acute abdominal pain, which presented as acute mesenteric ischemia combined with abdominal aortic dissection. Echocardiography showed enlargement of the aortic root and mitral valve prolapse. Abdominal computed tomography scan revealed acute mesenteric ischemia due to abdominal aortic dissection. Finally, the patient underwent surgery of aortic root replacement and had a successful outcome. Therefore, we suggest that for optimal risk assessment and monitoring of patients with Marfan syndrome, both aortic stiffness and the diameter of the superior mesenteric vein compared with that of the superior mesenteric artery are useful screening methods to detect acute mesenteric ischemia secondary to abdominal aortic dissection. Early diagnosis and early treatment can decrease the high mortality rate of patients with Marfan syndrome.

  6. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

    Directory of Open Access Journals (Sweden)

    Jaleh Varshosaz

    2014-01-01

    Full Text Available The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  7. Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia

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    Hamid R. Sadeghnia

    2017-09-01

    Full Text Available Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L. petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH content, and antioxidant capacity (using FRAP assay were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001 and also oxidative stress markers (p < 0.01. Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity.

  8. Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation.

    Science.gov (United States)

    Huang, Lifa; Chen, Chengwei; Zhang, Xin; Li, Xu; Chen, Zupeng; Yang, Chao; Liang, Xiaolong; Zhu, Guochong; Xu, Zhen

    2018-01-01

    Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

  9. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  10. Posterior Cerebral Infarction following Loss of Guide Wire

    OpenAIRE

    Bugnicourt, Jean-Marc; Belhomme, Denis; Bonnaire, Bruno; Constans, Jean-Marc; Manaouil, Cécile

    2013-01-01

    Stroke after internal jugular venous cannulation typically leads to acute carotid or vertebral arteries injury and cerebral ischemia. We report the first case of delayed posterior cerebral infarction following loss of guide wire after left internal jugular venous cannulation in a 46-year-old woman with a history of inflammatory bowel disease. Our observation highlights that loss of an intravascular guide wire can be a cause of ischemic stroke in patients undergoing central venous catheterizat...

  11. Total flavonoid of Litsea coreana leve exerts anti-oxidative effects and alleviates focal cerebral ischemia/reperfusion injury

    OpenAIRE

    Dong, Shuying; Tong, Xuhui; Li, Jun; Huang, Cheng; Hu, Chengmu; Jiao, Hao; Gu, Yuchen

    2013-01-01

    In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered orally to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at differ...

  12. Validation of enhanced and dynamic computed tomography for cerebral ischemia

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    Ono, Kenichiro; Arimoto, Hirohiko; Wada, Kojiro; Takahara, Takashi; Shirotani, Toshiki; Shimizu, Akira [Japan Self-Defense Forces Central Hospital, Tokyo (Japan); Hatanaka, Kosuke [Japan Self-Defense Forces Medical School, Tokyo (Japan)

    2003-03-01

    This paper shows the usefulness of enhanced and dynamic CT for ischemic stroke patients. Sixteen patients with disturbance of consciousness or neurological sign who did not have low-density area on plain CT were selected for this study. We performed enhanced CT sequentially. Enhanced CT image, time-density curve and functional image were compared with final infarcted area and occlusion level of cerebral artery. Three patients whose enhanced CT images showed obvious laterality had occlusion of internal carotid (IC) or horizontal portion of middle cerebral artery (M1). Four of five patients whose functional image and time density curve revealed abnormal region had ischemia because of more peripheral vessel occlusion or IC stenosis. Others with no abnormality on all images had lacunar infarction or did not have infarction finally. Occlusion of cerebral artery proximal portion could be diagnosed only with enhanced CT images. If selected slice was fit to the lesion, more distant level of ischemic area could be determined 100% by time-density curve and functional image. This examination takes only about ten minutes without transferring the patient. Enhanced CT and dynamic scan is useful tool to determine the diagnosis and management for ischemic stroke patients. (author)

  13. Validation of enhanced and dynamic computed tomography for cerebral ischemia

    International Nuclear Information System (INIS)

    Ono, Kenichiro; Arimoto, Hirohiko; Wada, Kojiro; Takahara, Takashi; Shirotani, Toshiki; Shimizu, Akira; Hatanaka, Kosuke

    2003-01-01

    This paper shows the usefulness of enhanced and dynamic CT for ischemic stroke patients. Sixteen patients with disturbance of consciousness or neurological sign who did not have low-density area on plain CT were selected for this study. We performed enhanced CT sequentially. Enhanced CT image, time-density curve and functional image were compared with final infarcted area and occlusion level of cerebral artery. Three patients whose enhanced CT images showed obvious laterality had occlusion of internal carotid (IC) or horizontal portion of middle cerebral artery (M1). Four of five patients whose functional image and time density curve revealed abnormal region had ischemia because of more peripheral vessel occlusion or IC stenosis. Others with no abnormality on all images had lacunar infarction or did not have infarction finally. Occlusion of cerebral artery proximal portion could be diagnosed only with enhanced CT images. If selected slice was fit to the lesion, more distant level of ischemic area could be determined 100% by time-density curve and functional image. This examination takes only about ten minutes without transferring the patient. Enhanced CT and dynamic scan is useful tool to determine the diagnosis and management for ischemic stroke patients. (author)

  14. 5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.

    Science.gov (United States)

    Ya, Bai-Liu; Li, Hong-Fang; Wang, Hai-Ying; Wu, Fei; Xin, Qing; Cheng, Hong-Ju; Li, Wen-Juan; Lin, Na; Ba, Zai-Hua; Zhang, Ru-Juan; Liu, Qian; Li, Ya-Nan; Bai, Bo; Ge, Feng

    2017-01-01

    Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that

  15. Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition.

    Science.gov (United States)

    Wang, Jun; Li, Dan; Hou, Jincai; Lei, Hongtao

    2018-02-01

    Geniposide, an active component of Gardenia, has been reported to protect against cerebral ischemia in animals. Ginsenoside Rg1, a component of Panax notoginseng, is usually administered in combination with Gardenia for the treatment of acute ischemic stroke; however, there are unknown effects of ginsenoside Rg1 that require further investigation. In the present study, the effects of geniposide and ginsensoide Rg1 combination treatment on focal cerebral ischemic stroke were investigated. For in vivo analysis, male rats were separated into three groups, including the (control), model and geniposide + ginsenoside Rg1 groups (n=8 per group). A middle cerebral artery occlusion model was established as the model group. The treatment group was treated with geniposide (30 mg/kg, tail vein injection) + ginsenoside Rg1 (6 mg/kg, tail vein injection), and the model group received saline instead. Neurobehavioral deficits, infarct volume, brain edema, and the expression of microRNA (miR)‑155‑5p and CD11b by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry, were assessed following 24 h of ischemia. For in vitro analysis, BV2 mouse microglial cells were cultured and exposed to geniposide (40 µg/ml) + ginsenoside Rg1 (8 µg/ml) during various durations of oxygen‑glucose deprivation (OGD). The expression levels of miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 were detected by RT‑qPCR. The results demonstrated that increases in brain infarct volume, edema volume, CD11b‑positive cells and miR‑155‑5p levels were alleviated following geniposide + ginsenoside administration in rats exposed to ischemia. Furthermore, geniposide + ginsenoside Rg1 treatment suppressed the miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 expression levels in OGD‑injured BV2 microglial cells. The results of the present study demonstrated that tail vein administration of geniposide in combination with ginsenoside Rg1

  16. Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

    Science.gov (United States)

    Yan, Han; Mitschelen, Matthew; Toth, Peter; Ashpole, Nicole M; Farley, Julie A; Hodges, Erik L; Warrington, Junie P; Han, Song; Fung, Kar-Ming; Csiszar, Anna; Ungvari, Zoltan; Sonntag, William E

    2014-11-01

    Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

  17. Can cerebral blood flow measurement predict clinical outcome in the acute phase in patients with artherosclerotic occlusive carotid artery disease?

    International Nuclear Information System (INIS)

    Hokari, Masaaki; Yasuda, Hiroshi; Iwasaki, Motoyuki; Iwasaki, Yoshinobu; Abe, Satoru; Saito, Hisatoshi; Kuroda, Satoshi; Nakayama, Naoki

    2010-01-01

    It has been thought that the clinical course of patients with acute carotid occlusive disease depends on their collateral cerebral blood flow (CBF) and duration of ischemia. However, there have been few clinical reports to prove this hypothesis. Therefore, we performed CBF study in patients with artherosclerotic carotid occlusive disease in the very acute phase, and precisely assessed the prognosis of those patients under intensive medical therapy. This prospective study included a total of 44 patients (72±13 years) who were admitted to our hospital between April, 2007 and December, 2008. To evaluate their initial CBF, single photon emission computed tomography (SPECT) studies were performed within 6 hours after the onset. All patients included in this study were medically treated and were periodically followed up by neurological and radiological examination. Moreover, in patients with reduced CBF (ipsilateral CBF/contralateral CBF x 100: %CBF <80%), dobutamine-induce hyperdynamic therapy was performed. Multivariate analysis was performed to detect significant predictors for the occurrence of further cerebral infarction. Multivariate analysis showed that the occurrence of further infarction was associated with older age and smaller %CBF. Of 44 patients, 21 experienced further cerebral infarction within 10 days after onset. Fourteen out of 15 patients with %CBF <60% developed cerebral infarction. This study showed that the prognosis of the patients with artherosclerotic carotid occlusive disease in the acute phase is associated with their initial residual CBFs. It may be difficult to stop the developed cerebral infarction in those patients with %CBF <60% despite intensive medical therapy. (author)

  18. Hypoxic ischemia encephalopathy leading to external hydrocephalus and the cerebral atrophy: mechanism and differential diagnosis

    International Nuclear Information System (INIS)

    Huang Zhenglin; Mo Xiaorong

    2002-01-01

    Objective: It is a study of the mechanism and differential diagnosis of the infant external hydrocephalus and cerebral atrophy. Methods: In total 84 cases of neonatal hypoxic ischemia encephalopathy followed by infant external hydrocephalus were investigated, among which 26 patients gradually were found having developed cerebral atrophy in follow up. Results: Characteristic dilation of the frontal-parietal subarachnoid space and the adjacent cistern was noted on the CT images of the external hydrocephalus. CT revealed the enlarged ventricle besides the dilated subarachnoid space in the cases of cerebral atrophy, while these two entities were indistinguishable on CT in the early stage. Conclusion: Clinical manifestations make a major differential diagnosis of the external hydrocephalus and cerebral atrophy: tic and mild delayed development of locomotion over major presentation of external hydrocephalus, while cerebral atrophy is featured by remarkable dysnoesia and severe delayed development of locomotion. In addition, hemiplegia and increased muscular tension are presented in a few cases of cerebral atrophy

  19. Effect of different component ratio of Astragalus total saponins and Verbena total glycosides on the cerebral infarction area and serum biochemical indicators in the focal cerebral ischemia-reperfusion rat model

    Directory of Open Access Journals (Sweden)

    Erping Xu

    2017-05-01

    Full Text Available Our purpose is to study the effect of different component ratio of Astragalus Total Saponins (ATS and Verbena Total Glycosides (VTG on the cerebral infarction area and the serum biochemical indicators in the focal cerebral ischemia-reperfusion rat model. Compared with the model group, different component ratio of ATS and VTG could significantly improve the neurological deficit scores to the focal cerebral ischemia-reperfusion rat model, and the group of 7:3, 6:4, 5:5 got the best results; it could reduce the mortality of rat model to a certain extent, and the group of 5:5 group got the best results; it can significantly reduce the cerebral infarction area, and the group of 7:3, 5:5, 4:6 got the best results; it could significantly reduce the content of TNF-α, and the group of 8:2, 6:4 got the best results; it could significantly reduce the content of NO, and the group of 7:3, 5:5 got the best results; it could significantly increase the content of SOD, and the group of 6:4, 5:5 got the best results. This indicates that different component ratio of ATS and VTG may protect the damage of focal cerebral ischemia-reperfusion rat model to a certain extent, which are compared using the comprehensive weight method and the ratio of 5:5 was proved to be the optimal active ratio.

  20. Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury.

    Science.gov (United States)

    Wang, Yanzhe; He, Zhiyi; Deng, Shumin

    2016-01-01

    Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. UA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (Pprotective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect. UA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent.

  1. Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

    Directory of Open Access Journals (Sweden)

    Wanchao Yang

    Full Text Available Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg for 180 min. The mean artery pressure (MAP, blood gas, and cerebral blood flow (CBF were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4 expression. In rats treated with severe hypoxia (PaO2 50 mmHg, hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg; especially under mild hypoxemia (PaO2 > 60 mmHg, hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05. Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

  2. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow

    International Nuclear Information System (INIS)

    Furlow, T.W. Jr.

    1982-01-01

    Cerebral ischemia was produced in the rat by simultaneous occlusion of the vertebral and carotid arteries according to the method of Pulsinelli and Brierley (Stroke 10: 267, 1979). Local cerebral blood flow (CBF) was determined by polarographic and autoradiographic techniques. Hydrogen-clearance measurements showed that mean CBF fell in four monitored regions of the hemispheres to between 0.11 and 0.18 ml/g/min, being least in deep rostal gray, intermediate in superficial gray, and greatest in deep caudal gray. However, individual animals had local CBF in excess of 0.20 and even 0.30 ml/g/min, and no animal showed zero CBF. When animals were rendered hypotensive (MABP of 50 Torr) during vascular occlusion, mean CBF ranged between 0.03 and 0.10 ml/g/min in the same regional order. With hypotension, total arrest of flow occurred. Autoradiographic data confirmed the above findings and indicated adequate CBF to the lower brainstem. During vascular occlusion, sufficient CBF may be present ot sustain cerebral tissue as in animals with a well developed spinal circulation or an inadvertently patent vertebral artery

  3. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

    OpenAIRE

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neur...

  4. Effects of dexmedetomidine on microregional O2 balance during reperfusion after focal cerebral ischemia.

    Science.gov (United States)

    Chi, Oak Z; Grayson, Jeremy; Barsoum, Sylviana; Liu, Xia; Dinani, Aliraza; Weiss, Harvey R

    2015-01-01

    This study was performed to determine whether there is an association between microregional O2 balance and neuronal survival in cerebral ischemia-reperfusion using dexmedetomidine, an α2-adrenoreceptor agonist and a sedative. Rats were subjected to 1 hour middle cerebral artery occlusion and a 2-hour reperfusion. During reperfusion, normal saline (n = 14) or dexmedetomidine 1 μg/kg/minute (n = 14) was infused intravenously. At 2 hours of reperfusion, regional cerebral blood flow using (14)C-iodoantipyrine autoradiography, microregional arterial and venous (20-60 μm in diameter) O2 saturation (SvO2) using cryomicrospectrophotometry, and the size of cortical infarction were determined. Ischemia-reperfusion decreased microregional SvO2 (52.9 ± 3.7% vs. 61.1 ± .6%, P < .005) with increased variation or heterogeneity (P < .0001) with similar regional cerebral blood flow and O2 consumption. Dexmedetomidine during reperfusion decreased the heterogeneity of SvO2 that was analyzed with an analysis of variance (P < .01) and reported as coefficient of variation (100 × standard deviation/Mean) (11.8 vs. 16.4). The number of veins with O2 saturation less than 50% decreased with dexmedetomidine (13/80 vs. 27/81, P < .01). The percentage of cortical infarct in total cortex was smaller with dexmedetomidine (8.3 ± 2.2% vs. 12.6 ± 1.5%, P < .005). In the cerebral ischemic reperfused cortex, dexmedetomidine decreased the heterogeneity of SvO2 and the number of small veins with low O2 saturation suggesting improved microregional O2 supply/consumption balance. The improvement was accompanied by the reduced size of cortical infarction. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Posterior Cerebral Infarction following Loss of Guide Wire

    Directory of Open Access Journals (Sweden)

    Jean-Marc Bugnicourt

    2013-01-01

    Full Text Available Stroke after internal jugular venous cannulation typically leads to acute carotid or vertebral arteries injury and cerebral ischemia. We report the first case of delayed posterior cerebral infarction following loss of guide wire after left internal jugular venous cannulation in a 46-year-old woman with a history of inflammatory bowel disease. Our observation highlights that loss of an intravascular guide wire can be a cause of ischemic stroke in patients undergoing central venous catheterization.

  6. Clinical study of interventional therapy for acute cerebral infarction

    International Nuclear Information System (INIS)

    Xiang Guangze; Xiao Yiming; Wen Zhilin

    2004-01-01

    Objective: To evaluate the clinical efficacy and safety of interventional therapy for acute cerebral infarction. Method: Using urokinase, 35 patients with acute cerebral infarction within 24 hours were treated by intra-artery thrombolytic therapy. Europe stroke scale (ESS), Barthel index (BI) were used to evaluate the recovery of neurological functions. Result: ESS score increase rapidly after thrombolytisis, and there were significant difference between the two teams. Thirteen of 13 cases treated within 6 hours from onset showed complete/partial recanalization in cerebral angiography and intraparenchymal hemorrhagic rate were 0%, twenty-six of 35 cases treated within 24 hours showed complete/partial recanalization and intraparenchymal hemorrhagic rate were 5.71%. Conclusion: Interventional therapy for acute cerebral infarction within 6h were safe and effective. (authors)

  7. Cerebral edema associated with acute hepatic failure.

    OpenAIRE

    Fujiwara, Masachika; Watanabe, Akiharu; Yamauchi, Yasuhiko; Hashimoto, Makoto; Nakatsukasa, Harushige; Kobayashi, Michio; Higashi, Toshihiro; Nagashima, Hideo

    1985-01-01

    The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64%) of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more fre...

  8. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  9. Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats

    Directory of Open Access Journals (Sweden)

    Leila Safaeian

    2015-01-01

    Conclusion: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion . However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human.

  10. Delayed Cerebral Ischemia following to Repair of Penetrating Trauma to External Carotid artery Introduction

    Directory of Open Access Journals (Sweden)

    M. Eskandarlou

    2016-01-01

    Full Text Available Introduction: Penetrating trauma to anterior neck can induce cerebral ischemia due to carotid artery injury. Brain ischemia also can present after surgical carotid repairs. Early diagnosis and suitable treatment modality prevent from permanent neurologic deficit post operatively. Case Report: A 30 years old man with stab wound to zone two left side of neck underwent exploration and penrose insertion. Due to excessive bleeding through drain tube, patient was transferred to Besat Hospital of Hamadan. Surgical repair of external carotid artery successfully was done. Four days later patient developed right hemiparesis suddenly. According to MRI and color Doppler sonography finding of thrombosis of left common and internal carotid artery, reoperation was done. After thrombectomy cerebral ischemia and hemi-paralysis improved. Conclusions: Surgical approach to symptomatic penetrating neck trauma is oblique cervical incision, control of bleeding, repair of internal carotid, repair or ligature of external carotid artery base on some factors and preferential repair of internal jugular vein. Meticulous and fine surgical technique for both vascular repair and protection of adjacent normal vessels for avoiding to blunt trauma or compression with retractors is noticeable. Exact postoperative care as repeated clinical examination with goal of early diagnosis of internal carotid artery thrombosis and rapid diagnostic and treatment planning of this complication are important factors for taking of good result in treatment of penetrating trauma to carotid. Sci J Hamadan Univ Med Sci . 2016; 22 (4 :353-357

  11. Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia

    International Nuclear Information System (INIS)

    Kuroda, Satoshi; Sakuragi, Mitsugi; Motomiya, Mineo; Nakagawa, Tango; Mitsumori, Kenji; Tsuru, Mitsuo; Takigawa, Shugo; Kamiyama, Hiroyasu; Abe, Hiroshi.

    1990-01-01

    Tests using 133 Xe inhalation method and single photon emission computed tomography (SPECT) with acetazolamide (Diamox) were performed in 23 patients with chronic cerebral ischemia, before and after extracranial-intracranial bypass surgery or carotid-endarterectomy. All patients complained of TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery. Cerebral blood flow (CBF) was measured with 133 Xe SPECT, and was measured 15 minutes after intravenous administration of 10-12 mg/kg Diamox, which is known as a cerebral vasodilatory agent (Diamox test). Our results revealed that all patients could be divided into four types according to their resting rCBF and Diamox reactivity. The patients who had normal resting rCBF and normal Diamox reactivity (type 1) were considered to have well-developed collateral circulation and normal cerebral perfusion pressure (CPP) in spite of severe occlusive lesions in the carotid system. Moderate vasodilation due to reduced CPP was considered to occur in patients who had normal resting rCBF and decreased Diamox reactivity (type 2). The resting rCBF remained unchanged, but Diamox reactivity improved to normal after surgery in the patients of type 2, which indicated the improvement of CPP and the resolution of the autoregulatory vasodilation. Maximum vasodilation or dysautoregulation was considered to occur due to the inadequate collateral flow and the severely reduced CPP in patients whose findings revealed decrease in the resting rCBF and impaired Diamox reactivity (type 3). Remarkable improvement was seen in both resting rCBF and Diamox reactivity after surgery in the patients of type 3. In the patients who had decreased resting rCBF and normal Diamox reactivity (type 4), the decreased resting rCBF was considered to result from the reduction in metabolic demand because of irreversible ischemic neuronal damage. (J.P.N.)

  12. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    OpenAIRE

    Najmeh Kabiri; Mahbubeh Setorki

    2016-01-01

    The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

  13. Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yanzhe Wang, Zhiyi He, Shumin Deng Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Background: Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. Methods: The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. Results: UA-treated (5, 10, or 20 mg/kg rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01. Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01. Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01 but an increased level of TIMP1 (P<0.01. UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a

  14. Acute limb ischemia caused by incorrect deployment of a clip-based arterial closure device

    Directory of Open Access Journals (Sweden)

    Łukasz Dzieciuchowicz

    2016-04-01

    Full Text Available Failure of a vascular closure device most commonly results in a hemorrhage or pseudoaneurysm formation. In this paper a rare case of severe acute limb ischemia following incorrect deployment of a clip-based closure device (Starclose SE, Abbott Vascular in a 31-year-old woman is presented. Symptoms of acute limb ischemia occurred at the start of the ambulation, 6 h after completion of the procedure. Because of the severity of ischemia the patient was treated surgically, and limb perfusion was successfully restored. An attempt of closure of an inadvertently punctured narrow superficial femoral artery was identified as the cause of this complication.

  15. Profiles of cortical tissue depolarization in cat focal cerebral ischemia in relation to calcium ion homeostasis and nitric oxide production.

    Science.gov (United States)

    Ohta, K; Graf, R; Rosner, G; Heiss, W D

    1997-11-01

    Cortical depolarization was investigated in a topographic gradient of ischemic density after 1-hour transient middle cerebral artery occlusion in halothane-anesthetized cats. A laser Doppler flow probe, an ion-selective microelectrode, and a nitric oxide (NO) electrode measured regional CBF (rCBF), direct current (DC) potential, extracellular Ca2+ concentration ([Ca2+]o), and NO concentration in ectosylvian and suprasylvian gyri of nine animals. Recordings revealed 12 of 18 sites with persistent negative shifts of the DC potential, severe rCBF reduction, and a drop of [Ca2+]o characteristic for core regions of focal ischemia. Among these sites, two types were distinguished by further analysis. In Type 1 (n = 5), rapid, negative DC shifts resembled anoxic depolarization as described for complete global ischemia. In this type, ischemia was most severe (8.9 +/- 2.5% of control rCBF), [Ca2+]o dropped fast and deepest (0.48 +/- 0.20 mmol/L), and NO concentration increased transiently (36.1 +/- 24.0 nmol/L at 2.5 minutes), and decreased thereafter. In Type 2 (n = 7), the DC potential fell gradually over the first half of the ischemic episode, rCBF and [Ca2+]o reductions were smaller than in Type 1 (16.2 +/- 8.2%; 0.77 +/- 0.41 mmol/L), and NO increased continuously during ischemia (53.1 +/- 60.4 nmol/L at 60 minutes) suggesting that in this type NO most likely exerts its diverse actions on ischemia-threatened tissue. In the remaining six recording sites, a third type (Type 3) attributable to the ischemic periphery was characterized by minimal DC shifts, mild ischemia (37.2 +/- 13.3%), nonsignificant alterations of [Ca2+]o, but decreased NO concentrations during middle cerebral artery occlusion. Reperfusion returned the various parameters to baseline levels within 1 hour, the recovery of [Ca2+]o and NO concentration being delayed in Type 1. An NO synthase inhibitor (N(G)-nitro-L-arginine, 50 mg/kg intravenously; four animals) abolished NO elevation during ischemia. In

  16. Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

    International Nuclear Information System (INIS)

    Schock, Sarah C.; Edrissi, Hamidreza; Burger, Dylan; Cadonic, Robert; Hakim, Antoine; Thompson, Charlie

    2014-01-01

    Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells

  17. Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Schock, Sarah C. [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Edrissi, Hamidreza [University of Ottawa, Neuroscience Graduate Program, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Burger, Dylan [Ottawa Hospital Research Institute, Kidney Centre, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Cadonic, Robert; Hakim, Antoine [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Thompson, Charlie, E-mail: charliet@uottawa.ca [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada)

    2014-07-18

    Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells.

  18. Improved assessment of outcomes following transient global cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Spray, Stine; Edvinsson, Lars

    2016-01-01

    by limited neurological assessment protocols and present insufficient reporting of the cumulative survival rate. Therefore, we aim at developing a reproducible and easily implementable model of transient GCI in mice with minimal impact on normal mouse behavior. GCI was induced in male C57BL/6 mice......Mouse models of global cerebral ischemia (GCI) allow experimental examination of cerebral pathophysiology in genetically modified mice and fast screening of new treatment strategies. Various surgical protocols of GCI-induction in mice have been published; however, many of these studies are hindered...... and again daily for up to 7 days after GCI or sham operation and was found to be significantly decreased 1-7 days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7 days after GCI but not at day 3 or after sham operation. The survival...

  19. Reactive Hippocampal Astrocytes Display an Increased Expression of Trpv4 Channels After Cerebral Hypoxia/Ischemia

    Czech Academy of Sciences Publication Activity Database

    Butenko, Olena; Džamba, Dávid; Prajerová, Iva; Benešová, Jana; Honsa, Pavel; Benfenati, V.; Ferroni, S.; Anděrová, Miroslava

    2011-01-01

    Roč. 59, Supplement 1 (2011), S126-S127 ISSN 0894-1491. [European meeting on Glia l Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50520701 Keywords : TRPV4 * astrocytes * cerebral hypoxia/ischemia Subject RIV: FH - Neurology

  20. The potential roles of metallothionein as a therapeutic target for cerebral ischemia and retinal diseases.

    Science.gov (United States)

    Ito, Yasushi; Tanaka, Hirotaka; Hara, Hideaki

    2013-01-01

    Methallothionein (MT) is a low molecular weight cysteine rich metalloprotein. In mammals, there are four isoforms (MT-1, -2, -3, and -4) and they have multiple roles, such as the detoxification of heavy metals, regulating essential metal homeostasis, and protecting against oxidative stress. Recently, accumulating studies have suggested that MTs (especially MT-1, -2, and -3) are an important neuroprotective substance for cerebral ischemia and retinal diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), that are characterized by a progressive retinal degeneration. Oxidative stress and/or zinc toxicity has been implicated as part of the common pathway in these diseases. Studying the expression patterns and functions of MTs may broaden our understanding of the endogenous molecular responses that these diseases trigger, and may help us to develop new therapeutic strategies to treat them. However, the precise roles of MTs within the brain and retina are not fully understood in terms of neuropathological conditions. In this review, we discuss the recent findings focusing on MTs' functions following cerebral ischemia, AMD, and RP.

  1. Convergent and divergent pathways decoding hierarchical additive mechanisms in treating cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Zhang, Ying-Ying; Li, Hai-Xia; Chen, Yin-Ying; Fang, Hong; Yu, Ya-Nan; Liu, Jun; Jing, Zhi-Wei; Wang, Zhong; Wang, Yong-Yan

    2014-03-01

    Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance. We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities. We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions. These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations. © 2013 John Wiley & Sons Ltd.

  2. Comparison between cerebral ischemia disease and multiple sclerosis by using MR diffusion tensor imaging

    International Nuclear Information System (INIS)

    Lou Xin; Cai Youquan; Ma Lin; Cai Jianming

    2007-01-01

    Objective: To assess the value of MR diffusion tensor imaging (DTI) in the differentiation between the patients with cerebral ischemia disease and multiple sclerosis. Methods: MR diffusion tensor imaging was performed in thirty-two patients with internal carotid artery stenosis ≥70% and eighteen patients with clinical diagnosed multiple sclerosis. Fractional anisotropy (FA) value of the germ, splenium, body of the corpus callosum, and the white matter of the frontal and occipital lobe were measured respectively, and independent-sample t-test statistical analysis was performed. Results: The FA value was decreased obviously in the anterior and posterior body and splenium of the corpus callosumin the MS patients compared with the ICA severe stenosis patients (0.67 ± 0.12 vs. 0.75 ± 0.05, t=3.443, P 0.05; 0.34 ± 0.08 vs. 0.34 ± 0.05, t=0.137, P> 0.05; 0.29 ± 0.06 vs. 0.40 ± 0.06, t=5.449, P>0.05). Conclusion: DTI can noninvasive detect the potential disorder of corpus callosum in vivo, thus providing useful information to differentiate the cerebral ischemia disease from multiple sclerosis. (authors)

  3. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

    Science.gov (United States)

    Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

    2016-10-29

    Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

  4. Spreading depolarization-modulating drugs and delayed cerebral ischemia after subarachnoid hemorrhage : A hypothesis-generating retrospective clinical study

    NARCIS (Netherlands)

    Hamming, Arend M.; Mulder, Inge A.; Gathier, Celine S.; van den Bergh, Walter M.; Dankbaar, Jan Willem; Hoff, Reinier G.; Vandertop, W. Peter; Verbaan, Dagmar; Ferrari, Michel D.; Rinkel, Gabriel J. E.; Algra, Ale; Wermer, Marieke J. H.

    2016-01-01

    Background: Delayed cerebral ischemia (DCI) occurs in approximately one-third of patients with aneurysmal subarachnoid hemorrhage (aSAH). A proposed underlying mechanism for DCI is spreading depolarization (SD). Our aim was to, retrospectively, investigate the influence of the use of SD-modulating

  5. Ilexonin A Promotes Neuronal Proliferation and Regeneration via Activation of the Canonical Wnt Signaling Pathway after Cerebral Ischemia Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Bi-Qin Zhang

    2016-01-01

    Full Text Available Aims. Ilexonin A (IA, a component of the Chinese medicine Ilex pubescens, has been shown to be neuroprotective during ischemic injury. However, the specific mechanism underlying this neuroprotective effect remains unclear. Methods. In this study, we employed a combination of immunofluorescence staining, western blotting, RT-PCR, and behavioral tests, to investigate the molecular mechanisms involved in IA regulation of neuronal proliferation and regeneration after cerebral ischemia and reperfusion in rodents. Results. Increases in β-catenin protein and LEF1 mRNA and decreases in GSK3β protein and Axin mRNA observed in IA-treated compared to control rodents implicated the canonical Wnt pathway as a key signaling mechanism activated by IA treatment. Furthermore, rodents in the IA treatment group showed less neurologic impairment and a corresponding increase in the number of Brdu/nestin and Brdu/NeuN double positive neurons in the parenchymal ischemia tissue following middle cerebral artery occlusion compared to matched controls. Conclusion. Altogether, our data indicate that IA can significantly diminish neurological deficits associated with cerebral ischemia reperfusion in rats as a result of increased neuronal survival via modulation of the canonical Wnt pathway.

  6. Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

    Directory of Open Access Journals (Sweden)

    Yanier Núñez Figueredo

    2016-08-01

    Full Text Available Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.

  7. Aortic plaque rupture in the setting of acute lower limb ischemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2012-02-01

    Acute aortic plaque rupture is an uncommon cause of acute lower limb ischemia. The authors report sequence computed tomographic imaging of a distal aortic plaque rupture in a young man with bilateral lower limb complications. Clinical awareness, prompt recognition and imaging, and appropriate treatment of this uncommon condition are necessary to improve patient outcomes.

  8. Glatiramer Acetate administration does not reduce damage after cerebral ischemia in mice.

    Science.gov (United States)

    Poittevin, Marine; Deroide, Nicolas; Azibani, Feriel; Delcayre, Claude; Giannesini, Claire; Levy, Bernard I; Pocard, Marc; Kubis, Nathalie

    2013-01-15

    Inflammation plays a key role in ischemic stroke pathophysiology: microglial/macrophage cells and type-1 helper cells (Th1) seem deleterious, while type-2 helper cells (Th2) and regulatory T cells (Treg) seem protective. CD4 Th0 differentiation is modulated by microglial cytokine secretion. Glatiramer Acetate (GA) is an immunomodulatory drug that has been approved for the treatment of human multiple sclerosis by means of a number of mechanisms: reduced microglial activation and pro-inflammatory cytokine production, Th0 differentiation shifting from Th2 to Th2 and Treg with anti-inflammatory cytokine production and increased neurogenesis. We induced permanent (pMCAo) or transient middle cerebral artery occlusion (tMCAo) and GA (2 mg) or vehicle was injected subcutaneously immediately after cerebral ischemia. Mice were sacrificed at D3 to measure neurological deficit, infarct volume, microglial cell density and qPCR of TNFα and IL-1β (pro-inflammatory microglial cytokines), IFNγ (Th2 cytokine), IL-4 (Th2 cytokine), TGFβ and IL-10 (Treg cytokines), and at D7 to evaluate neurological deficit, infarct volume and neurogenesis assessment. We showed that in GA-treated pMCAo mice, infarct volume, microglial cell density and cytokine secretion were not significantly modified at D3, while neurogenesis was enhanced at D7 without significant infarct volume reduction. In GA-treated tMCAo mice, microglial pro-inflammatory cytokines IL-1β and TNFα were significantly decreased without modification of microglial/macrophage cell density, cytokine secretion, neurological deficit or infarct volume at D3, or modification of neurological deficit, neurogenesis or infarct volume at D7. In conclusion, Glatiramer Acetate administered after cerebral ischemia does not reduce infarct volume or improve neurological deficit in mice despite a significant increase in neurogenesis in pMCAo and a microglial pro-inflammatory cytokine reduction in tMCAo. Copyright © 2012 Elsevier B.V. All rights

  9. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Hailong Yu

    Full Text Available Carvacrol (CAR, a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion. This neuroprotection was in a dose-dependent manner. Post-treatment with CAR still provided protection on infarct volume when it was administered intraperitoneally at 2 h after reperfusion; however, intracerebroventricular post-treatment reduced infarct volume even when the mice were treated with CAR at 6 h after reperfusion. These findings indicated that CAR has an extended therapeutic window, but delivery strategies may affect the protective effects of CAR. Further, we found that CAR significantly decreased the level of cleaved caspase-3, a marker of apoptosis, suggesting the anti-apoptotic activity of CAR. Finally, our data indicated that CAR treatment increased the level of phosphorylated Akt and the neuroprotection of CAR was reversed by a PI3K inhibitor LY-294002, demonstrating the involvement of the PI3K/Akt pathway in the anti-apoptotic mechanisms of CAR. Due to its safety and wide use in the food industry, CAR is a promising agent to be translated into clinical trials.

  10. [Adipose-derived stem cell transplantation promotes the expression of netrin-1 in the rat cortex after focal cerebral ischemia].

    Science.gov (United States)

    Wang, Jiehua; Hong, Zhuquan; Pan, Ying; Li, Guoqian

    2017-01-01

    Objective To observe the effect of adipose-derived stem cells (ADSCs) transplantation on the expression of netrin-1 in rats after focal cerebral ischemia. Methods Male SD rats were randomly divided into control group, model group and ADSC group. ADSCs were harvested and purified. Focal cerebral ischemia models were established in rats by the suture method. ADSCs were injected into the lateral ventricle of ADSC group rats and the same does of PBS was given to model group rats. At day 4, 7 and 14 after reperfusion, six rats were sacrificed to remove the brain tissues at each time point. The expression of netrin-1 was detected by reverse-transcription PCR, Western blotting and immunohistochemistry. Results Compared with the control group, the expression of netrin-1 in the brain tissues of the model group increased after focal cerebral ischemia, reached the peak at 4 days, and the expression of netrin-1 was significantly higher than that of the control group at each time point. Compared with the model group, the expression of netrin-1 in the ADSC group increased further, reached the peak at 7 days, and the expression of netrin-1 in the ADSC group was significantly higher than that of the model group at each time point. Conclusion ADSC transplantation could up-regulate the expression of netrin-1, and promote axon regeneration and the recovery of neurological functions.

  11. Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

    OpenAIRE

    Ding, Qiao; Liao, Song-Jie; Yu, Jian

    2014-01-01

    Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light o...

  12. Analysis of arterial pressure variability in patients with acute cerebral stroke depending on the time of occurrence

    Directory of Open Access Journals (Sweden)

    Volosovets A.O.

    2017-12-01

    Full Text Available Arterial hypertension can cause a pronounced negative influence on the state of the cerebral vascular system and lead to significant microtraumatization of the walls of the vessels and disruption of vascular autoregulation. This predictor has the greatest influence on the onset of ischemic stroke of atherothrombotic and lacunar subtypes, however, hypertension occurs almost in all patients with acute cerebral ischemia. Interesting and not at all presented in modern scientific literature is the question of the relationship of oscillation of blood pressure with the period of the onset of the focus of ischemia, which predetermined the purpose of our work. The purpose of our study was to determine the relationship between deformation of the profile of fluctuations in blood pressure of patients in the acute period of ischemic stroke, depending on the time of the occurrence of cerebrovascular accident. We examined 300 patients who suffered acute ischemic stroke (men - 196, women - 104 aged 42 to 84 years (average age - 65.2 ± 8.7 years. All patients were divided into 3 groups according to the period of the day when an ischemic stroke occurred: 1 group (n=146, patients suffering from cerebral ischemia during the day (8.00-14.59; In group 2 (n=107, patients stroke was observed in the evening (15.00-21.59; Group 3 (n=47, patients had an ischemic stroke at night (22.00-7.59. For the 1st group of patients who have had ischemic stroke during the day and as a rule with an increase in blood pressure, a marked increase in blood pressure was at 12.00 and 15.00 and a tendency towards compensatory parasympathetic effect in the form of blood pressure decrease at night (over-dipper was typical. At the same time, in the 2nd group of patients with stroke in the evening, elevated blood pressure at 18.00 and 21.00 and parasympathetic activity disorders with prevalence of insufficient reduction of blood pressure in the evening and during sleep (non-dipper was observed

  13. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Mousavi Nia

    2017-03-01

    Full Text Available Background: Nepeta dschuparensis Bornm (NP is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2 and interleukin-1β (IL-1β protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. Methods: Twenty-six male rats were randomly divided into 3 groups: 1 sham (n=6: no middle cerebral artery occlusion (MCAO procedure, 2 control (n=10: MCAO procedure and treatment with normal saline, and 3 NP extract (n=10: MCAO procedure and treatment with the NP extract (20 mg/kg, i.p. at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1β and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01. Results: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1β and COX-2 protein levels too (P<0.01. Conclusion: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1β and COX-2.

  14. Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Chen, Qingwen; Edvinsson, Lars

    2009-01-01

    BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metallopr......BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression...

  15. Watershed Cerebral Infarction in a Patient with Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak

    2016-02-01

    Full Text Available Acute renal failure can cause neurologic manifestations such as mood swings, impaired concentration, tremor, stupor, coma, asterixis, dysarthria. Those findings can also be a sign of cerebral infarct. Here, we report a case of watershed cerebral infarction in a 70-year-old female patient with acute renal failure secondary to contrast administration and use of angiotensin converting enzyme inhibitor. Patient was evaluated with magnetic resonance imaging because of dysarthria. Magnetic resonance imaging revealed milimmetric acute ischemic lesion in the frontal and parietal deep white matter region of both cerebral hemisphere which clearly demonstrated watershed cerebral infarction affecting internal border zone. Her renal function returned to normal levels on fifth day of admission (BUN 32 mg/dl, creatinine 1.36 mg/dl and she was discharged. Dysarthria continued for 20 days.

  16. Acute cerebral vascular accident associated with hyperperfusion

    International Nuclear Information System (INIS)

    Soin, J.S.; Burdine, J.A.

    1976-01-01

    Cerebral radionuclide angiography can demonstrate decreased or normal radioactivity in the affected region during the arterial phase in patients who have sustained a cerebral vascular accident and thus enhances the diagnostic specificity of the static brain image. In an occasional patient, however, a seemingly paradoxical pattern of regional hyperperfusion with a return to normal or subnormal perfusion following the acute phase has been observed. This phenomenon, called luxury perfusion, has been defined using intra-arterial 133 Xe for semiquantitative cerebral blood flow measurements and should be kept in mind as a potentially misleading cerebral imaging pattern

  17. Acute mesenteric ischemia of arterial origin: importance of early revascularization.

    Science.gov (United States)

    Plumereau, F; Mucci, S; Le Naoures, P; Finel, J B; Hamy, A

    2015-02-01

    The goal of our study was to show that survival was better when early revascularization was performed rather than gastrointestinal resection in the management of acute mesenteric ischemia of arterial origin. The reports of patients managed in our center between January 2005 and May 2012 for acute mesenteric ischemia of arterial origin were analyzed retrospectively. Data on clinical, laboratory and radiologic findings, the interval before treatment, the operative findings and the surgical procedures were collected. Follow-up information included the postoperative course, and mortality at 48 h, 30 days and 1 year, the latter being compared between patients undergoing revascularization versus gastrointestinal resection. Of 43 patients treated during this period, 20 had gastrointestinal lesions deemed to be beyond all therapeutic resources, 13 were treated with gastrointestinal resection without revascularization, while 10 underwent early revascularization. There were no statistically significant differences found in the extent of involvement between the two groups (P=0.22). Mortality at 48 h, 30 days and 1 year was 8% (n=1), 30% (n=4) and 68% (n=8) in patients who underwent enterectomy vs. 0% (n=0), 0% (n=0) and 10% (n=1) in patients who underwent revascularization procedures. The difference at 1 year was statistically significant (P=0.02). At 1 year, two patients in the revascularized group had a short bowel syndrome vs. one in the non-revascularized group. Acute mesenteric ischemia of arterial origin is associated with high morbidity and mortality. Optimal management should include early revascularization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. PET imaging of cerebral perfusion and oxygen consumption in acute ischemic stroke: Relation to outcome

    International Nuclear Information System (INIS)

    Marchal, G.; Serrati, C.; Rioux, P.; Petit-Taboue, M.C.; Viader, F.; Sayette, V. de la; Doze, F. le; Lonchon, P; Derlon, J.M.; Orgogozo, J.M.; Baron, J.C.

    1993-01-01

    The authors used positron emission tomography (PET) to assess the relation between combined imaging of cerebral blood flow and oxygen consumption 5-18 h after first middle cerebral artery (MCA) stroke and neurological outcome at 2 months. All 18 patients could be classified into three visually defined PET patterns of perfusion and oxygen consumption changes. Pattern 1 suggested extensive irreversible damage and was consistently associated with poor outcome. Pattern 2 suggested continuing ischemia and was associated with variable outcome. Pattern 3 with hyperperfusion and little or no metabolic alteration, was associated with excellent recovery, which suggests that early reperfusion is beneficial. This relation between PET and outcome was highly significant. The results suggest that within 5-18 h of stroke onset, PET is a good predictor of outcome in patterns 1 and 3, for which therapy seems limited. The absence of predictive value for pattern 2 suggests that it is due to a reversible ischemic state that is possibly amenable to therapy. These findings may have important implications for acute MCA stroke management and for patients' selection for therapeutic trials

  19. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  20. Radiologic manifestations of focal cerebral hyperemia in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Skriver, E B; Herning, M

    1991-01-01

    In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

  1. The Use of Milrinone in Patients with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage: A Systematic Review.

    Science.gov (United States)

    Lannes, Marcelo; Zeiler, Frederick; Guichon, Céline; Teitelbaum, Jeanne

    2017-03-01

    The purpose of this article is to provide a systematic review of the evidence supporting the use of milrinone for the management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). Primary outcomes were functional neurological status and the incidence of cerebral infarction. Search strategies adapted to the different databases were developed by a professional librarian. Medline, EMBASE, the Cochrane Library database, Web of Science, SCOPUS, BIOSIS, Global Health, Health Star, Open SIGLE, Google Scholar and the New York Academy of Medicine Gray Literature were searched as well as clinical trials databases and the proceedings of several scientific meetings. Quality of the evidence for these outcomes across studies was adjudicated using the GRADE Working Group criteria. The search resulted in 284 citations after elimination of duplicates. Of those 9 conference proceedings and 15 studies met inclusion criteria and consisted of case reports, case series and two comparative studies: one non-randomized study with physiological outcomes only and a case series with historical controls. There was considerable variation in dosing and in co-interventions and no case control or randomized controlled studies were found. There is currently only very low quality evidence to support the use of milrinone to improve important outcomes in patients with delayed cerebral ischemia secondary to subarachnoid hemorrhage. Further research is needed to clarify the value and risks of this medication in patients with SAH.

  2. Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

    2017-01-01

    This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

  3. Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

    Directory of Open Access Journals (Sweden)

    Maedeh Arabian

    2015-01-01

    Full Text Available Objective(s: Morphine dependence (MD potently protects heart against ischemia reperfusion (IR injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg or L-NAME (20 mg/kg 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P

  4. Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Kaur, Shaminder; Rehni, Ashish K; Singh, Nirmal; Jaggi, Amteshwar S

    2009-04-01

    The present study was designed to investigate the possible neuroprotective effect of digoxin induced pharmacological preconditioning (PP) and its probable mechanism. Bilateral carotid artery occlusion (BCAO) of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R) induced cerebral injury in male swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using elevated plus maze test. Degree of motor incoordination was evaluated using inclined beam walking test, rota rod test and lateral push test. Digoxin (0.08 mg/kg, i.p.) was administered 24 h before surgery in a separate group of animals to induce PP. BCAO followed by reperfusion, produced significant rise in cerebral infarct size along with impairment of memory and motor coordination. Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of I/R induced impairment of memory and motor incoordination. Digoxin induced neuroprotective effect was abolished significantly by verapamil (15 mg/kg, i.p.), a L-type calcium channel blocker, ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker and 3,4-dichlorobenzamil (Na(+)/Ca(2+) exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective effect on the ischemic brain, which is possibly linked to digitalis induced increase in intracellular calcium levels eventually leading to the activation of calcium sensitive signal transduction cascades.

  5. Preconditioning with the traditional Chinese medicine Huang-Lian-Jie-Du-Tang initiates HIF-1α-dependent neuroprotection against cerebral ischemia in rats.

    Science.gov (United States)

    Zhang, Qichun; Bian, Huimin; Li, Yu; Guo, Liwei; Tang, Yuping; Zhu, Huaxu

    2014-06-11

    Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1α (HIF-1α) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry. HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1α, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion. Both rats and neurons subjected to HLJDT preconditioning were able to resist ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and the enhancement of proliferation, and these effects were primarily dependent on the activation of the PI3K/Akt signaling pathway and HIF-1α. Copyright © 2014 Elsevier Ireland Ltd. All rights

  6. Contrast MR imaging of acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kogame, Saeko; Syakudo, Miyuki; Inoue, Yuichi (Osaka City Univ. (Japan). Faculty of Medicine) (and others)

    1992-04-01

    Thirty patients with acute and subacute cerebral infarction (13 and 17 deep cerebral infarction) were studied with 0.5 T MR unit before and after intravenous injection of Gd-DTPA. Thirteen patients were studied within 7 days after neurological ictus, 17 patients were studied between 7 and 14 days. Two types of abnormal enhancement, cortical arterial and parenchymal enhancement, were noted. The former was seen in 3 of 4 cases of very acute cortical infarction within 4 days after clinical ictus. The latter was detected in all 7 cases of cortical infarction after the 6th day of the ictus, and one patient with deep cerebral infarction at the 12th day of the ictus. Gd-DTPA enhanced MR imaging seems to detect gyral enhancement earlier compared with contrast CT, and depict intra-arterial sluggish flow which was not expected to see on contrast CT scans. (author).

  7. Hyperbaric oxygen in skeletal muscle of rats submitted to total acute left hindlimb ischemia: A research report.

    Science.gov (United States)

    da Silva, Luis Gustavo Campos; Dalio, Marcelo Bellini; Joviliano, Edwaldo Edner; Feres, Omar; Piccinato, Carlos Eli

    2015-01-01

    Determine the effect of hyperbaric oxygen treatment in skeletal muscle of rats submitted to total acute left hindlimb ischemia. An experimental study was designed using 48 Wistar rats divided into four groups (n = 12): Control; Ischemia (I)--total hindlimb ischemia for 270 minutes; Hyperbaric oxygen treatment during ischemia (HBO2)--total hindlimb ischemia for 270 minutes and hyperbaric oxygen during the first 90 minutes; Pre-treatment with hyperbaric oxygen (PHBO2)--90 minutes of hyperbaric oxygen treatment before total hindlimb ischemia for 270 minutes. Skeletal muscle injury was evaluated by measuring levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total creatine phosphokinase (CPK); muscular malondialdehyde (MDA), muscular glycogen, and serum ischemia-modified albumin (IMA). AST was significantly higher in I, HBO2 and PHBO2 compared with control (P = .001). There was no difference in LDH. CPK was significantly higher in I, HBO2 and PHBO2, compared with control (p = .014). MDA was significantly higher in PHBO2, compared with other groups (p = .042). Glycogen was significantly decreased in I, HBO2 and PHBO2, compared with control (p < .001). Hyperbaric oxygen treatment in acute total hindlimb ischemia exerted no protective effect on muscle injury, regardless of time of application. When applied prior to installation of total ischemia, hyperbaric oxygen treatment aggravated muscle injury.

  8. Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation.

    Science.gov (United States)

    Huang, Y C; Tzeng, W S; Wang, C C; Cheng, B C; Chang, Y K; Chen, H H; Lin, P C; Huang, T Y; Chuang, T J; Lin, J W; Chang, C P

    2013-09-01

    This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation. Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections. Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (Pagmatine-treated rats compared with the control ischemia rats (Pagmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Twin-twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

    Energy Technology Data Exchange (ETDEWEB)

    Kline-Fath, Beth M. [University of Cincinnati Medical Center, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Cincinnati Children' s Hospital, Department of Radiology, Cincinnati, OH (United States); Calvo-Garcia, Maria A.; O' Hara, Sara M.; Racadio, Judy M. [University of Cincinnati Medical Center, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Crombleholme, Timothy M. [University of Cincinnati Medical Center, Department of Surgery, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States)

    2007-01-15

    Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. We describe the fetal MR imaging findings associated with TTTS. From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS. (orig.)

  10. Twin-twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

    International Nuclear Information System (INIS)

    Kline-Fath, Beth M.; Calvo-Garcia, Maria A.; O'Hara, Sara M.; Racadio, Judy M.; Crombleholme, Timothy M.

    2007-01-01

    Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. We describe the fetal MR imaging findings associated with TTTS. From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS. (orig.)

  11. [Study of neuron-protective effect and mechanism of neuregulin1β against cerebral ischemia reperfusion-induced injury in rats].

    Science.gov (United States)

    Ji, Y Q; Zhang, R; Teng, L; Li, H Y; Guo, Y L

    2017-07-18

    Objective: Thecurrent study is to explore the neuron-protective mechanism of neuregulin1β (NRG1β) in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) through inhibiting the c-Jun phosphorylation. Methods: After 24 h of MCAO/R (referring to Longa's method), neurobehavioral function was measured by modified neurological severity score (mNSS) test; the cerebral infarction volume was detected by triphenyltetrazolium chloride (TTC) staining; the blood brain barrier (BBB) permeability was measured by Evans Blue (EB); the neuron morphology of brain tissue was observed by Nissl stain; the ultra-structures of the neurons were observed by transmission electron microscopy (TEM); the apoptotic neurons were counted by in situ cell death detection kit colocalized with NeuN; the expressions of phospho-c-Jun was determined by immunofluorescent labeling and Western blot analysis. Results: Compared with the sham-operation rats, the rats receiving MCAO/R showed increased mNSS (9.7±1.2), cerebral infarction volume (41.4±3.0)%, permeability of BBB, deformation of neurons, ischemia-induced apoptosis (0.63±0.04), and enhanced expression of phospho-c-Jun protein (0.90±0.07) (all P <0.05). Our data indicated that NRG1β attenuated neurologic deficits (6.4±0.9), decreased the cerebral infarction volume (10.4±0.5), reduced EB extravasation (1.55±0.13) and the deformation of neurons, protected the ultra-structure of neurons, blocked ischemia-induced apoptosis (0.23±0.02), through down-regulated phospho-c-Jun expression (0.40±0.03) in MCAO/R rats ( P <0.05). Conclusion: NRG1β exerts neuron-protective effects against ischemia reperfusion-induced injury in rats through inhibiting the c-Jun phosphorylation.

  12. Clinical effectiveness of percutaneous angioplasty for acute and chronic mesenteric ischemia: a six case series.

    Science.gov (United States)

    Jung, Yu Min; Jo, Yun Ju; Ahn, Sang Bong; Son, Byoung Kwan; Kim, Seong Hwan; Park, Young Sook; Bae, June Ho; Cho, Young Kwon

    2011-04-01

    Intestinal ischemia is divided into three categories, namely, acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), and colonic ischemia. AMI can result from arterial or venous thrombi, emboli, and vasoconstriction secondary to low-flow states. It is an urgent condition which can result in high mortality rate. The predominant causative factor of CMI is stenosis or occlusion of the mesenteric arterial circulation, and it is characterized by postprandial abdominal pain and weight loss. Surgery is the treatment of choice for intestinal ischemia. However, it has been recently reported that percutaneous transluminal angioplasty with stent placement and/or thrombolysis is an effective therapy in various types of mesenteric ischemia. We report six cases of mesenteric ischemia which were successfully treated by percutaneous angioplasty, and review the literature from South Korea.

  13. Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

    2017-07-01

    The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p zinc administration and markedly by chronic zinc supplementation.

  14. Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2014-05-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Anatolii V Dobrodumov,4 Anastasiy S Dayneko,5 Alexey A Shmonin,5,6 Timur D Vlasov,5 Elena V Melnikova,5 Alexander D Vilisov,4,5 Irina V Guzhova,1 Alexander M Ischenko,3 Anastasiya L Mikhrina,7 Oleg V Galibin,5 Igor V Yakovenko,2 Boris A Margulis1 1Institute of Cytology of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 2AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia; 3Research Institute of Highly Pure Biopreparations, St Petersburg, Russia; 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 5First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia; 6Federal Almazov Medical Research Centre, St Petersburg, Russia; 7IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, Russia Abstract: Recombinant 70 kDa heat shock protein (Hsp70 is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg. To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia. Rats were then kept alive for 72 hours. The

  15. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia

    OpenAIRE

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M.; McCullough, Louise; Andreasson, Katrin

    2008-01-01

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE2 receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE2 EP2, EP3, and EP4 receptors, would reduce brain injury in the murine m...

  16. Relative Abundance of Proteins in Blood Plasma Samples from Patients with Chronic Cerebral Ischemia.

    Science.gov (United States)

    Kaysheva, Anna L; Kopylov, Artur T; Ponomarenko, Elena A; Kiseleva, Olga I; Teryaeva, Nadezhda B; Potapov, Alexander A; Izotov, Alexander А; Morozov, Sergei G; Kudryavtseva, Valeria Yu; Archakov, Alexander I

    2018-03-01

    A comparative protein profile analysis of 17 blood plasma samples from patients with ischemia and 20 samples from healthy volunteers was carried out using ultra-high resolution mass spectrometry. The analysis of measurements was performed using the proteomics search engine OMSSA. Normalized spectrum abundance factor (NSAF) in the biological samples was assessed using SearchGUI. The findings of mass spectrometry analysis of the protein composition of blood plasma samples demonstrate that the depleted samples are quite similar in protein composition and relative abundance of proteins. By comparing them with the control samples, we have found a small group of 44 proteins characteristic of the blood plasma samples from patients with chronic cerebral ischemia. These proteins contribute to the processes of homeostasis maintenance, including innate immune response unfolding, the response of a body to stress, and contribution to the blood clotting cascade.

  17. [Effect of Tongluo Xingnao effervescent tablets on learning and memory dysfunction in rats with chronic cerebral ischemia].

    Science.gov (United States)

    Hu, Yong; Ju, Shao-Hua; Zhang, Yin-Jie; Xiong, Min; Xu, Shi-Jun; Ma, Yun-Tong; Zhong, Zhen-Dong

    2014-05-01

    To study the effect of Tongluo Xingnao effervescent tablets on learning and memory capacity and expression of Na(+)-K(+)-ATPase in hippocampus of rats with chronic cerebral ischemia-induced learning and memory dysfunction model. The 2-VO method was used to establish sd rat model learning and memory dysfunction induced by chronic cerebral ischemia. The 50 rats in the successfully established model were randomly divided into the model control group, the Dihydroergotoxine Mesylate tablets group (0.7 mg x kg(-1), Tongluo Xingnao effervescent tablets high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups and the sham operation group (n = 10) as the control group. The groups were orally given 10 ml x kg(-1) x d(-1) drugs for consecutively 90 days. On the 86th day, Morris water maze was adopted for them. On the 90th day, a leaning and memory capacity test was held. The brain tissues were fixed with 10% formaldehyde and observed for pathomorphism after routine slide preparation and staining. The expression of hippocampal Na(+)-K(+)-ATPase was detected with immunohistochemistry and image quantitative analysis. Compared with the model group, all of Tongluo Xingnao effervescent tablets groups showed significant decrease in the escape latency at the 5th day in the Morris water maze, and notable increase in the frequency of the first quadrant dwell, the frequency passing the escape platform and the frequency entering effective area (p tablets can improve the learning and memory capacity, reduce pathological changes of hippocampal tissues of rats with chronic cerebral ischemia-induced learning and memory dysfunction model, and promote the expression of Na(+)-K(+)-ATPase in hippocampus.

  18. Accuracy of multidetector row computed tomography for the diagnosis of acute bowel ischemia in a non-selected study population

    International Nuclear Information System (INIS)

    Wiesner, Walter; Hauser, Andreas; Steinbrich, Wolfgang

    2004-01-01

    The diagnostic accuracy of multidetector row computed tomography for the prospective diagnosis of acute bowel ischemia in the daily clinical routine was analyzed. Two hundred ninety-one consecutive patients with an acute or subacute abdomen, examined by MDCT over a time period of 5 months, were included in the study. All original CT diagnoses made during the daily routine by radiological generalists were compared to the final diagnoses made by using all available medical information from endoscopies, surgical interventions, autopsies and follow-up. Finally, all CT examinations of patients with an initial CT diagnosis or a final diagnosis of bowel ischemia were reread by a radiologist specialized in abdominal imaging in order to analyze the CT findings and the reasons for initially false negative or false positive CT readings. Twenty-four patients out of 291 (8.2%) had acute bowel ischemia. The age of affected patients ranged from 50 to 94 years (mean age: 75.7 years). Eleven patients were male, and 13 female. Reasons for acute bowel ischemia were: arterio-occlusive (n=11), non-occlusive (n=5), strangulation (n=2), over-distension (n=3) and radiation (n=3). The prospective sensitivity, specificity, PPV and NPV of MDCT for the diagnosis of acute bowel ischemia in the daily routine were 79.17, 98.51, 90.48 and 98.15%. MDCT reaches a similarly high sensitivity in diagnosing acute bowel as angiography. Furthermore, it has the advantage of being helpful in most of its clinical differential diagnoses and of being less invasive with the consecutive possibility of being used earlier in the diagnostic process with all the resulting positive effects on the patients prognosis. Therefore, nowadays MDCT should probably be used as the first step imaging modality of choice in patients with suspected acute bowel ischemia. (orig.)

  19. Multi-detector CT features of acute intestinal ischemia and their prognostic correlations.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-05-28

    Acute intestinal ischemia is an abdominal emergency occurring in nearly 1% of patients presenting with acute abdomen. The causes can be occlusive or non occlusive. Early diagnosis is important to improve survival rates. In most cases of late or missed diagnosis, the mortality rate from intestinal infarction is very high, with a reported value ranging from 60% to 90%. Multi-detector computed tomography (MDCT) is a fundamental imaging technique that must be promptly performed in all patients with suspected bowel ischemia. Thanks to the new dedicated reconstruction program, its diagnostic potential is much improved compared to the past and currently it is superior to that of any other noninvasive technique. The increased spatial and temporal resolution, high-quality multi-planar reconstructions, maximum intensity projections, vessel probe, surface-shaded volume rending and tissue transition projections make MDCT the gold standard for the diagnosis of intestinal ischemia, with reported sensitivity, specificity, positive and negative predictive values of 64%-93%, 92%-100%, 90%-100% and 94%-98%, respectively. MDCT contributes to appropriate treatment planning and provides important prognostic information thanks to its ability to define the nature and extent of the disease. The purpose of this review is to examine the diagnostic and prognostic role of MDCT in bowel ischemia with special regard to the state of art new reconstruction software.

  20. Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Fakhri, Yama; Sejersten, Maria; Schoos, Mikkel Malby

    2018-01-01

    inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary...

  1. Hypoperfusion Induced by Preconditioning Treadmill Training in Hyper-Early Reperfusion After Cerebral Ischemia: A Laser Speckle Imaging Study.

    Science.gov (United States)

    He, Zhijie; Lu, Hongyang; Yang, Xiaojiao; Zhang, Li; Wu, Yi; Niu, Wenxiu; Ding, Li; Wang, Guili; Tong, Shanbao; Jia, Jie

    2018-01-01

    Exercise preconditioning induces neuroprotective effects during cerebral ischemia and reperfusion, which involves the recovery of cerebral blood flow (CBF). Mechanisms underlying the neuroprotective effects of re-established CBF following ischemia and reperfusion are unclear. The present study investigated CBF in hyper-early stage of reperfusion by laser speckle contrast imaging, a full-field high-resolution optical imaging technique. Rats with or without treadmill training were subjected to middle cerebral artery occlusion followed by reperfusion. CBF in arteries, veins, and capillaries in hyper-early stage of reperfusion (1, 2, and 3 h after reperfusion) and in subacute stage (24 h after reperfusion) were measured. Neurological scoring and 2,3,5-triphenyltetrazolium chloride staining were further applied to determine the neuroprotective effects of exercise preconditioning. In hyper-early stage of reperfusion, CBF in the rats with exercise preconditioning was reduced significantly in arteries and veins, respectively, compared to rats with no exercise preconditioning. Capillary CBF remained stable in the hyper-early stage of reperfusion, though it increased significantly 24 h after reperfusion in the rats with exercise preconditioning. As a neuroprotective strategy, exercise preconditioning reduced the blood perfusion of arteries and veins in the hyper-early stage of reperfusion, which indicated intervention-induced neuroprotective hypoperfusion after reperfusion onset.

  2. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    Directory of Open Access Journals (Sweden)

    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

  3. Zinc translocation accelerates infarction after mild transient focal ischemia.

    Science.gov (United States)

    Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

    2002-01-01

    Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

  4. Diagnostic Value of Procalcitonin Levels in Acute Mesenteric Ischemia

    Directory of Open Access Journals (Sweden)

    Yunus Karaca

    2015-09-01

    Full Text Available Background: Acute mesenteric ischemia (AMI is a potentially fatal disease. Difficulties in diagnosis make it essential to find early biomarkers. Aims: This study investigated the diagnostic value of procalcitonin (PCT levels in AMI. Study Design: Animal experimentation. Methods: Rats were divided into six groups of six animals each. In the experimental group, an experimental ischemia model was established by clamping the superior mesenteric artery from the aortic outflow tract. Blood and tissue specimens were collected from rats in the experimental mesenteric ischemia model at 30 min and 2 and 6 h, and these were compared with specimens from the respective control groups. PCT levels were compared at 30 min and 2 and 6 h. Results: PCT levels were 185.3 pg/mL in the control group and 219.3 pg/mL in the study group, 199.6 pg/mL in the control group and 243.9 pg/mL in the study group, and 201.9 pg/mL in the control group and 286.9 pg/mL in the study group, respectively, at 30 minute, 2 and 6 hours. Significant differences were determined between 6-h control group and ischemia group PCT levels (p=0.005. Conclusion: The absence of a significant increase in PCT levels in the early period, while a significant difference was detected in the later period (6 h, shows that PCT levels rise late in mesenteric ischemia and can be a marker in the late period.

  5. Revascularization for acute mesenteric ischemia.

    Science.gov (United States)

    Ryer, Evan J; Kalra, Manju; Oderich, Gustavo S; Duncan, Audra A; Gloviczki, Peter; Cha, Stephen; Bower, Thomas C

    2012-06-01

    Acute mesenteric ischemia (AMI) remains difficult to diagnose, carries a high rate of complications, and is associated with significant mortality. We evaluated our experience with AMI over the last 2 decades to evaluate changes in management and assess current outcomes. Data from consecutive patients who underwent arterial revascularization for AMI over a 20-year period (January 1990-January 2010) were retrospectively reviewed. Patient demographics, treatment modalities, and outcomes over the last decade (2000-2010) were compared with those of the preceding decade (1990-1999) previously reported. Over the last 2 decades, 93 patients with AMI underwent emergency arterial revascularization. Forty-five patients were treated during the 1990s and 48 during the 2000s. The majority of these patients were transferred from outside facilities. Patient demographics and risk factors were similar between the 2 decades with the exception that the more contemporary patients were significantly older (65.1 ± 14 vs 71.3 ± 14; P = .04). Etiology remained constant between the groups with in situ thrombosis being the most common followed by arterial embolus. The majority of patients were treated with open revascularization. Endovascular therapy alone or as a hybrid procedure was used in 11 total patients, eight of which were treated in the last 10 years. The use of second-look laparotomy was much more liberal in the last decade (80% vs 48%; P = .003) Thirty-day mortality was 27% in the 1990s and 17% during the 2000s (P = 0.28). Major adverse events occurred in 47% of patients with no difference between decades. There was no significant difference in outcomes between open and endovascular revascularization. On univariate analysis, elevated SVS comorbidity score, congestive heart failure, and chronic kidney disease predicted early death, while a history of chronic mesenteric ischemia appeared protective. On multivariate analysis, no factor independently predicted perioperative

  6. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  7. [Cerebral ischemia in Rendu-Osler-Weber disease].

    Science.gov (United States)

    Delgado Reyes, S; García de la Rocha, M L; Fernández-Armayor Ajo, V; Sierra Sierra, I; Martín Araguz, A; Moreno Martínez, J M

    2000-02-01

    Neurologic manifestations occur in 8-12% of the patients with Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT), principally infectious and hemorrhagic and, less frequently, ischemic ones. More than a half of these neurologic complications are associated with pulmonary arterio-venous malformations (PAVM). The diagnosis of HHT is based on the presence of telangiectases, hemorrhagic events and a family history with an autosomal dominant pattern. We report a case of a patient diagnosed as having HHT with transient ischemic attacks and a PAVM, which was occluded by the use of embolotherapy. Cerebral ischemia in HHT is related to the existence of a PAVM and results from three mechanisms: 1) secondary poliglobulia and hyperviscosity because of the hypoxemia due to a right-left shunt; 2) communication between the airway and the pulmonary circulation during cough access, which produces gas embolism and hemoptysis; 3) and, finally, paradoxical embolism trough the PAVM, the same mechanism proposed to the infectious neurologic manifestations of the disease. When the diagnosis of HHT is suspected, early search and treatment of PAVM, with embolotherapy or surgery, are necessary in order to avoid respiratory problems (hemoptysis, exertional dyspnea, cianosis, clubbing) and neurologic complications.

  8. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    International Nuclear Information System (INIS)

    Zhu, Haibo; He, Jie; Ye, Liang; Lin, Fei; Hou, Jian; Zhong, Yan; Jiang, Wanglin

    2015-01-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  9. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Haibo [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); He, Jie [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Ye, Liang [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); Lin, Fei; Hou, Jian; Zhong, Yan [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Jiang, Wanglin, E-mail: jwl518@163.com [School of Pharmaceutical Sciences, Institute of Materia Medica, Binzhou Medical University, Yantai (China)

    2015-11-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  10. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

    2011-01-01

    Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

  11. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

    2011-01-01

    Tumour necrosis factor-a (TNF-a) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-a acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-a and TNF-a receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

  12. Toll-like receptor 2 promotes neurogenesis from the dentate gyrus after photothrombotic cerebral ischemia in mice.

    Science.gov (United States)

    Seong, Kyung-Joo; Kim, Hyeong-Jun; Cai, Bangrong; Kook, Min-Suk; Jung, Ji-Yeon; Kim, Won-Jae

    2018-03-01

    The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

  13. THE FATE OF MDACH1-EXPRESSING CELLS IN THE DORSAL PART OF THE LATERAL VENTRICLES FOLLOWING FOCAL CEREBRAL ISCHEMIA

    Czech Academy of Sciences Publication Activity Database

    Anděrová, Miroslava; Pivoňková, Helena; Honsa, Pavel

    2013-01-01

    Roč. 61, Supplement 1 (2013), S125-S126 ISSN 0894-1491. [European Meeting on Glia l Cell Function in Health and Disease /11./. 03.07.2013-06.07.2013, Berlin] Institutional support: RVO:68378041 Keywords : cerebral ischemia * neuroscience * MDACH1 Subject RIV: FH - Neurology

  14. [Cerebral protection].

    Science.gov (United States)

    Cattaneo, A D

    1993-09-01

    Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

  15. Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt.

    Science.gov (United States)

    Chai, Yu-Shuang; Hu, Jun; Lei, Fan; Wang, Yu-Gang; Yuan, Zhi-Yi; Lu, Xi; Wang, Xin-Pei; Du, Feng; Zhang, Dong; Xing, Dong-Ming; Du, Li-Jun

    2013-05-15

    Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. [Cerebral artery infarction presented as an unusual complication of acute middle otitis].

    Science.gov (United States)

    Moscote-Salazar, Luis Rafael; Alcalá-Cerra, Gabriel; Castellar-Leones, Sandra Milena; Gutiérrez-Paternina, Juan José

    2013-01-01

    acute otitis media is a frequent disease in the pediatric age. About 2 % of all cases develop intracranial complications such as meningitis. The cerebral infarction originates meningitis and usually occurs in the venous system. The presence of a cerebral artery infarction secondary to acute otitis media is a rare cause described in the literature. a girl of 12 months who presented a febrile syndrome due to acute otitis media and mental confusion. On physical examination, she appeared sleepy with anisocoria, mydriasis in the right eye and left hemiparesis. The computed tomography examination showed extensive cerebral artery infarction. The patient's parents refused the proposed surgical treatment and the girl died 48 hours later. regardless of the current technological advances, the clinical prognosis of cerebral infarction associated with acute otitis media is bad. The focused neurological signs and progressive clinical deterioration should raise suspicion that antimicrobial therapy is not effective.

  17. Neuroprotective effects of the AMPA antagonist PNQX in oxygen-glucose deprivation in mouse hippocampal slice cultures and global cerebral ischemia in gerbils

    DEFF Research Database (Denmark)

    Montero, Maria; Nielsen, Marianne; Rønn, Lars Christian B

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in tr......PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD......) and in transient global cerebral ischemia in gerbils. For in vitro studies, hippocampal slice cultures derived from 7-day-old mice and grown for 14 days, were submersed in oxygen-glucose deprived medium for 30 min and exposed to PNQX for 24 h, starting together with OGD, immediately after OGD, or 2 h after OGD...... stained for the neurodegeneration marker Fluoro-Jade B and immunostained for the astroglial marker glial fibrillary acidic protein revealed a significant PNQX-induced decrease in neuronal cell death and astroglial activation. We conclude that, PNQX provided neuroprotection against both global cerebral...

  18. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  19. Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice

    OpenAIRE

    He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2013-01-01

    Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral te...

  20. Intra-Carotid Urokinase thrombolytic therapy in acute cerebral infarction: a preliminary study

    International Nuclear Information System (INIS)

    Cho, Hee Kyung; Chung, Tae Sub; Kim, Dong Ik; Suh, Jung Ho; Lee, Byung In; Lee, Byung Chul

    1990-01-01

    We conducted a pilot study to evaluate the possibility that the intraarterial thrombolytic therapy might lead to recanalization of the acutely occluded cerebral arteries and subsequent clinical improvement in patients with acute cerebral infarction. Mean time from the onset of symptoms to the start of treatment and mean dosage of thrombolytic agent, Urokinase, were 6.4 hours and 1,260,000 units, respectively. Seven of 12 cases (58%) with acute cerebral infarction demonstrated successful recanalization. Neurological evaluation at one week and three months after the onset of symptoms suggested better outcome in the cases with recanalization. Repeat CT scan at 24 hours and one week after the procedure demonstrated the evidence of hemorrhagic infarction in the infarcted territories in five cases (41%), but clinical deteriorations were observed in only 2 cases. Though statistical analysis could not be done because the limited number of cases, these results suggest that the intraarterial thrombolytic therapy had a role in the management of acute cerebral infarction

  1. [Identification of early irreversible damage area in a rat model of cerebral ischemia and reperfusion].

    Science.gov (United States)

    Liu, S; Guo, Y

    2000-02-01

    To observe the early neuron ischemic damage in focal cerebral ischemia/reperfusion with histostaining methods of argyrophil III (AG III), Toludine blue(TB), and H&E, and to make out the 'separating line' between the areas of reversible and irreversible early ischemic damage. Forty-two male Wistar rats were randomly divided into the following groups: pseudo-surgical, blank-control, O2R0(occluded for 2 hours and reperfused for 0 hour), O2R0.5, O2R2, O2R4, O2R24. There were 6 rats in each group. Rats in experimental groups were suffered focal cerebral ischemia/reperfusion through a nylon suture method. After a special processor for tissue manage, the brain were coronal sectioned and stained with H&E, TB, and AG III. The area where dark neurons dwell in (ischemic core) were calculated with image analysis system. The success rate of ischemic model for this experiment is 90%. After being stained with argyrophil III method, normal neurons appear yellow or pale brown, which is hardly distinguished from the pale brown background. The ischemic neuron stained black, and has collapsed body and "corkscrew-like" axon or dentries, which were broken to some extent. The neuropil in the dark neurons dwelt area appears gray or pale black, which is apparently different from the pale brown neighborhood area. The distribution of dark neurons in cortex varies according to different layers, and has a character of columnar form. The dark neurons present as early as 2 hours ischemia without reperfusion with AG III method. AG III stain could selectively display early ischemic neurons, the area dwelt by dark neurons represent early ischemic core. Dark neuron is possibly the irreversibly damaged neuron. Identification of dark neurons could be helpful in the discrimination between early ischemic center and penumbra.

  2. Breviscapine confers a neuroprotective efficacy against transient focal cerebral ischemia by attenuating neuronal and astrocytic autophagy in the penumbra.

    Science.gov (United States)

    Pengyue, Zhang; Tao, Guo; Hongyun, He; Liqiang, Yang; Yihao, Deng

    2017-06-01

    Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group. The autophagy levels in infarct penumbra were evaluated by western blotting, real-time PCR and immunofluorescence 7days after the insult. Meanwhile, infarct volume, brain water content and neurological deficit score were assessed. The results illustrated that the infarct volume, brain water content and neurofunctional deficiency were significantly reduced by 7days of breviscapine treatment in MCAO+Bre group, compared with those in MCAO+saline group. Meanwhile, the western blotting, quantitative PCR and immunofluorescence showed that the autophagy in both neurons and astrocytes at the penumbra were markedly attenuated by breviscapine admininstration. Moreover, these pharmacological effects of breviscapine could be counteracted by autophagy inducer Tat-Beclin-1. Our study suggests that breviscapine can provide a neuroprotection against transient focal cerebral ischemia, and this biological function is associated with attenuating autophagy in both neurons and astrocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Evidence that Patent Foramen Ovale is not a Risk Factor for Cerebral Ischemia in the Elderly

    Science.gov (United States)

    Jones, Elizabeth F.; Calafiore, Paul; Donnan, Geoffrey A.; Tonkin, Andrew M.

    1994-01-01

    Patent foramen ovale (PFO) may be a risk factor for ischemic stroke in young patients. The aim of this study was to assess the importance of PFO in subjects with a wider age range using patient-control methodology. Transesophageal contrast echocardiography and carotid imaging were performed in 220 consecutive patients with cerebral ischemia (mean age 66 +/- 13 years) and in 202 community-based control subjects (mean age 64 +/- 11 years). Of patients with stroke, 35 (16%) had PFO compared with 31 control subjects (15%) (p = 0.98). Analysis of PFO prevalence by age did not show a significant difference between patients and control subjects in the age groups or equal to 70 years (12% vs 17%; p = 0.43). However, the group aged 450 years was relatively small (26 cases, 19 controls). No significant difference in PFO prevalence was detected between patients with cryptogenic stroke (20%), noncryptogenic stroke (14%), and control subjects (15%). These results suggest that PFO is not a risk factor for cerebral ischemia in subjects aged >50 years, which would have major implications for the investigation and management of stroke patients in this age group. Longitudinal studies are now required to assess the incidence of stroke in symptom free patients with PFO.

  4. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Babcock, Alicia

    2009-01-01

    Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical...

  5. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

    Science.gov (United States)

    Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

    2006-11-01

    Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

  6. Statins in acute neurologic disease:which one, which dose, when to start, and when not to stop

    Institute of Scientific and Technical Information of China (English)

    Bong-Su Kang; Gene Sung; May Kim-Tenser; Nerses Sanossian

    2016-01-01

    Statins could have physiologic properties that may beneift patients that have been diagnosed with various acute neurological diseases. This review aims tosummarize the literature pertaining to stain use in acute neurological disease such as subarachnoid hemorrhage, intracerebral hemorrhage (ICH), cerebral ischemia (CI), traumatic brain injury, status epilepticus and meningitis. The authors reviewed published abstracts and manuscripts pertaining to experimental and clinical trials relevant to statins in acute neurological disease. Although acute statin therapy in the setting of subarachnoid hemorrhage might reduce delayed cerebral ischemia and mortality, it should not be considered standard care at this time. Acute statins therapy has not demonstrated anybeneift yet folowing an ICH or CI. Acute statin withdrawal may worsen outcome in acute CI. Observational and case-control studies suggest that pretreatment with statin at time of onset may be associated with better outcomes. Even though preclinical studies have shown statins to have beneifcial effects, there has been no clinical evidence. In conclusion, current published studies have not shown that acute statin therapy has any beneifcal effects in acute neurologic diseases and therefore further large randomized clinical trials are needed.

  7. Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.

    Science.gov (United States)

    Rosow, David E; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I; Mueller, Peter R; Fernández-del Castillo, Carlos; Warshaw, Andrew L; Thayer, Sarah P

    2005-12-01

    Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings--compared with pathologic diagnoses-- predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

  8. Silent ischemia in patients after the acute myocardial infarction

    International Nuclear Information System (INIS)

    Samarzija, M.

    1991-01-01

    The purpose of this study was to determine the frequency and importance of silent ischemia in patients (pts) after acute myocardial infarction (AMI) as well as to establish diagnostic and prognostic values of exercise stress test (EST), Holter (H) monitoring and thallium-201 (Tl) scintigraphy. All the tests were performed 2-4 months following the AMI. The criterion for diagnostic myocardial ischemia on EST and H is 1 mm or more of horizontal or down-sloping ST depression. Additional criteria for Holter imply that the ischemic episode should last one minute and be separated from other episodes by at least one minute. Planar thallium images were performed 5-10 minutes after the stress test; the delayed images were obtained after 3-6 hours. Visual and quantitative methods were employed in the analysis of Tl-scintigraphy. Scintigraphy was considered positive if exercise-induced perfusion defects showed redistribution. The study included 74 asymptomatic patients after the AMI. The patients were divided into two groups by results of quantitative Tl-scintigraphy: Group I - 44 pts with silent ischemia, Group II - 30 pts without ischemia. In Group I, out of 44 pts, 9 had a positive exercise stress test, 4 showed a painless ST depression on Holter and 7 had both tests positive, whereas 24 pts had only scintigraphy positive. In Group II one patient had positive EST and H. Sensitivity and specificity were determined by results of coronary arteriography performed on 33 pts: EST (Se=40%, Sp=80%), H (Se=21%, Sp=100%) and scintigraphy (Se=93%, Sp=80%). During the follow-up period lasting at least 12 months, in Group I 3 pts died, 1 developed a new myocardial infarction and 15 pts had painful ischemic occurrences. In Group II only 3 pts developed symptoms of angina pectoris. Tl-scintigraphy was the only non-invasive test showing significant correlation with the follow-up outcomes. The diagnostic and prognostic superiority of Tl-scintigraphy justifies its value as an initial

  9. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    Science.gov (United States)

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  10. MRI of experimental focal cerebral ischemia in sheep; MR-Bildgebung eines experimentellen Schlaganfallmodells beim Schaf

    Energy Technology Data Exchange (ETDEWEB)

    Foerschler, A. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Abt. fuer Neuroradiologie; Boltze, J. [Universitaetsklinikum Leipzig (Germany). Inst. fuer Klinische Immunologie und Transfusionsmedizin; Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Waldmin, D. [Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Gille, U. [Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Zimmer, C. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Abt. fuer Neuroradiologie

    2007-05-15

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2{sup *} sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 {+-} 5.7; 13; 1.7 {+-} 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  11. Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda

    2016-01-01

    Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor...... reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6...... knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display...

  12. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    Directory of Open Access Journals (Sweden)

    Eun Joo Bae

    2015-01-01

    Full Text Available The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1- 3 between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

  13. Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia; Measurement of cerebral blood volume (CBV) with sup 99m Tc-RBC SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Satoshi; Sakuragi, Mitsugi; Motomiya, Mineo; Nakagawa, Tango; Mitsumori, Kenji; Tsuru, Mitsuo (Hokkaido Neurosurgical Memorial Hospital (Japan)); Takigawa, Shugo; Kamiyama, Hiroyasu; Abe, Hiroshi

    1990-03-01

    To evaluate the efficacy of tests for selecting patients with hemodynamic compromise, measurement of cerebral blood volume (CBV) with {sup 99m}Tc-RBC single photon emission computed tomography (SPECT) was performed in thirteen patients with occlusive cerebrovascular disease, and was compared with results obtained by {sup 133}Xe SPECT and acetazolamide (Diamox) test. All patients in our study suffered TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery, although plain CT scan or MRI revealed no or, if any, only localized infarcted lesions. Regional cerebral blood volume (rCBV) was measured with {sup 99m}Tc-RBC SPECT and regional cerebral blood flow (rCBF) was measured with {sup 133}Xe SPECT before and after intravenous injection of 10 - 12 mg/kg acetazolamide (Diamox). Our results suggest that the ipsilateral rCBV/rCBF (mean transit time) is a more sensitive index of the cerebral perfusion reserve than the use of only rCBV or rCBF of the ipsilateral hemisphere. Also, the ipsilateral rCBV/rCBF is significantly correlated (r= -0.72) with the Diamox reactivity of rCBF, which is considered to represent the cerebral vasodilatory capacity in patients with chronic cerebral ischemia. Postoperative SPECT study revealed remarkable improvement of ipsilateral rCBV/rCBF and Diamox reactivity in four patients who underwent EC/IC bypass surgery to improve the hemodynamic compromise. In conclusion, our results suggest that the measurement of rCBV/rCBF with {sup 133}Xe SPECT and {sup 99m}Tc-RBC SPECT is useful for detecting the hemodynamic compromise in patients with occlusive cerebrovascular disease. (author).

  14. Persistent sciatic artery aneurysm: A rare cause of acute limb ischemia

    Directory of Open Access Journals (Sweden)

    Pranay Pawar

    2018-01-01

    Full Text Available Persistent sciatic artery (PSA is a rare but pertinent clinical entity that may pose a threat to the viability of the lower extremity. The incidence of PSA has been estimated to be between 0.01% and 0.05%. PSAs are prone to high incidence of aneurysm formation, thrombosis, distal embolization, and rupture. Early detection of a PSA as the main vascular supply to the lower limb helps in early surgery and avoids potential severe complications such as limb ischemia. We report a case of a female patient who was diagnosed with a case of lumbar disc compression and sciatica but had a PSA aneurysm with thrombosis and distal embolization leading to acute limb ischemia.

  15. Manual Aspiration Thrombectomy in Patients with Acute Stroke-Related Calcified Cerebral Emboli.

    Science.gov (United States)

    Koh, Esther; Kwak, Hyo Sung; Chung, Gyung-Ho

    2017-10-01

    The aim of this study was to evaluate the effectiveness of mechanical aspiration thrombectomy (MAT) in patients with acute ischemic stroke from calcified cerebral emboli. Procedural results were reviewed for acute stroke patients with clinically neurological deficits who underwent recanalization from October 2012 through September 2015. Initial imaging studies and cerebral angiography were analyzed. Of the total number of patients with acute stroke, 5 patients were confirmed to have acute ischemic stroke by calcified cerebral emboli. On initial brain computed tomographic imaging, all patients showed small, dense single calcifications in the middle cerebral artery with no definitive ischemic low-density lesions (M1: 3, M2: 2, mean size: 4.8 mm). All patients had angiographic findings of filling defects from calcified emboli. Four patients had good collateral flow and two had continuous distal flow. All patients underwent MAT using a Penumbra catheter (Penumbra Inc., Alameda, CA). MAT did not remove calcified emboli in all patients. Two patients with good collateral flow had favorable functional outcomes (modified Rankin Scale score ≤2). Four patients had diffuse calcification in the aortic arch, carotid artery, and aortic valve. Cerebral angiography supports a diagnosis of stroke when calcified cerebral emboli have contrast-filling defects and a degree of vascular occlusion. However, in this study, MAT was not an effective treatment for patients with calcified cerebral emboli because of hardness of the calcified plaque and packing into the arterial lumen. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Current status and outlook of endovascular therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Li Minghua; Zhao Jungong

    2005-01-01

    Improvement of diagnostic technology and increasing advent of new materials for intervention has created a new area for endovascular therapy of cerebral ischemic diseases. Current research findings have shown that endovascular thrombolysis in acute stage of cerebral infarction can accelerate the rate of re-canalization of occluded arteries and greatly decrease the morbidity and mortality of cerebral ischemic vascular diseases. Stenting of arterial stenosis can the improve of blood supply distal to the lesion, prevent recurrent cerebral ischemic stroke. As a result, endovascular thrombolysis for acute cerebral infarction and stenting for intracranial and carotid arterial stenosis are booming both at home and abroad. Proper selection of patients of acute cerebral infarction for endovascular thrombolysis with less complications could be achieved through CT perfusion, MR perfusion-weighted image (PWI) and diffusion-weighted image (DWI), non-invasive vascular imaging technology including CEMRA and CTA for confirming and demonstrating the sites and causes of cerebral ischemia, and furthermore for evaluating the survival ability and etc. The research team administered albumin and magnesium sulfate as neurological protection drug to treat rat infarction model within 6 hours of onset resulting with the same effect of decreasing the damage of ischemic cerebral tissue and without hemorrhagic complication. It is certain that hemorrhagic complication in thrombolysis is a result of multiple factors with no single drug being able to solve the problem. It is predictable that, based on semi-quantitative or quantitative parameters of CT or MRI in conjunction with PWI/DWI mismatch model rather than simply on the onset time of infarction for proper selection of patients of cerebral infarction, mechanic thrombus-disruption and/or intra-arterial thrombolysis together with intervention of neurological protection drug will be the trend for treating acute cerebral infarction in the future

  17. HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA) : a randomized single- blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage

    NARCIS (Netherlands)

    Gathier, C. S.; van den Bergh, W. M.; Slooter, A. J. C.

    RationaleDelayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article

  18. HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage

    NARCIS (Netherlands)

    Gathier, C. S.; van den Bergh, W. M.; Slooter, A. J. C.; Algra, Ale; Beute, Gus N.; Coert, Bert A.; Dankbaar, Jan-Willem; Dippel, Diederik; Dirven, Clemens M. F.; Gathier, Celine S.; Horn, Janneke; van der Jagt, Mathieu; Kesecioglu, Jozef; van Kooten, Fop; van der Lugt, Aad; Muller, Marcella C. A.; Oldenbeuving, Annemarie W.; van der Pol, Bram; Regli, Luca; Rinkel, Gabriel J. E.; Roks, Gerwin; van der Schaaf, Irene C.; Slooter, Arjen J. C.; Vandertop, W. Peter; Verweij, Bon H.

    2014-01-01

    Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes

  19. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  20. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    Directory of Open Access Journals (Sweden)

    Najmeh Kabiri

    2016-09-01

    Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

  1. Drug-Induced Hypothermia as Beneficial Treatment before and after Cerebral Ischemia

    DEFF Research Database (Denmark)

    Johansen, Flemming F; Hasseldam, Henrik; Rasmussen, Rune Skovgaard

    2014-01-01

    Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when...... conditioning before (preconditioning) and after (postconditioning) experimental stroke. Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature...... was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced...

  2. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

    Science.gov (United States)

    Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

    2018-05-03

    Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

  3. Acute Cerebral Insufficiency in Patients with Severe Forms of Alcoholic Psychoses

    Directory of Open Access Journals (Sweden)

    V. V. Zverev

    2006-01-01

    Full Text Available The paper summarizes the results of studies of cerebral metabolism in 38 patients with delirium tremens. The findings have led to the conclusion that the leading factor of the pathogenesis of acute cerebral insufficiency in this case is energy deficiency caused by impaired cerebral glucose utilization rather than hypoxia itself.

  4. Neuronal nitric oxide synthase inhibition prevents cerebral palsy following hypoxia-ischemia in fetal rabbits: comparison between JI-8 and 7-nitroindazole.

    Science.gov (United States)

    Yu, Lei; Derrick, Matthew; Ji, Haitao; Silverman, Richard B; Whitsett, Jennifer; Vásquez-Vivar, Jeannette; Tan, Sidhartha

    2011-01-01

    Cerebral palsy and death are serious consequences of perinatal hypoxia-ischemia (HI). Important concepts can now be tested using an animal model of cerebral palsy. We have previously shown that reactive oxygen and nitrogen species are produced in antenatal HI. A novel class of neuronal nitric oxide synthase (nNOS) inhibitors have been designed, and they ameliorate postnatal motor deficits when administered prior to the hypoxic-ischemic insult. This study asks how the new class of inhibitors, using JI-8 (K(i) for nNOS: 0.014 μM) as a representative, compare with the frequently used nNOS inhibitor 7-nitroindazole (7-NI; K(i): 0.09 ± 0.024 μM). A theoretical dose equivalent to 75 K(i) of JI-8 or equimolar 7-NI was administered to pregnant rabbit dams 30 min prior to and immediately after 40 min of uterine ischemia at 22 days gestation (70% term). JI-8 treatment resulted in a significant decrease in NOS activity (39%) in fetal brain homogenates acutely after HI, without affecting maternal blood pressure and heart rate. JI-8 treatment resulted in 33 normal kits, 2 moderately and 13 severely affected kits and 5 stillbirths, compared with 8 normal, 3 moderately affected and 5 severely affected kits and 10 stillbirths in the 7-NI group. In terms of neurobehavioral outcome, 7-NI was not different from saline treatment, while JI-8 was superior to saline and 7-NI in its protective effect (p JI-8 significantly improved the locomotion score over both saline and 7-NI scores. JI-8 was also significantly superior to saline in preserving smell, muscle tone and righting reflex function, but 7-NI did not show significant improvement. Furthermore, a 100-fold increase in the dose (15.75 μmol/kg) of 7-NI significantly decreased systolic blood pressure in the dam, while JI-8 did not. The new class of inhibitors such as JI-8 shows promise in the prevention of cerebral palsy and is superior to the previously more commonly used nNOS inhibitor. Copyright © 2011 S. Karger AG, Basel.

  5. Acute hemifacial ischemia as a late complication of carotid stenting

    Directory of Open Access Journals (Sweden)

    Maurizio Domanin, MD

    2017-06-01

    Full Text Available Concerns about carotid artery stenting (CAS center primarily on procedural complications like acute occlusion, stroke, and long-term intrastent restenosis. External carotid artery (ECA thrombosis is observed during CAS follow-up, but it often remains asymptomatic or, at worst, results in jaw claudication. We report here a case of late occlusion of the ECA after CAS with symptoms of acute homolateral facial ischemia as well as pain, cyanosis, tongue numbness, and skin coldness. The patient was submitted to local thrombolysis and balloon angioplasty with regression of symptoms after recanalization. With this report, we add a caveat about blockage of the ECA ostium during CAS.

  6. Improved CT-detection of acute bowel ischemia using frequency selective non-linear image blending.

    Science.gov (United States)

    Schneeweiss, Sven; Esser, Michael; Thaiss, Wolfgang; Boesmueller, Hans; Ditt, Hendrik; Nikolau, Konstantin; Horger, Marius

    2017-07-01

    Computed tomography (CT) as a fast and reliable diagnostic technique is the imaging modality of choice for acute bowel ischemia. However, diagnostic is often difficult mainly due to low attenuation differences between ischemic and perfused segments. To compare the diagnostic efficacy of a new post-processing tool based on frequency selective non-linear blending with that of conventional linear contrast-enhanced CT (CECT) image blending for the detection of bowel ischemia. Twenty-seven consecutive patients (19 women; mean age = 73.7 years, age range = 50-94 years) with acute bowel ischemia were scanned using multidetector CT (120 kV; 100-200 mAs). Pre-contrast and portal venous scans (65-70 s delay) were acquired. All patients underwent surgery for acute bowel ischemia and intraoperative diagnosis as well as histologic evaluation of explanted bowel segments was considered "gold standard." First, two radiologists read the conventional CECT images in which linear blending was adapted for optimal contrast, and second (three weeks later) the frequency selective non-linear blending (F-NLB) image. Attenuation values were compared, both in the involved and non-involved bowel segments creating ratios between unenhanced and CECT. The mean attenuation difference between ischemic and non-ischemic wall in the portal venous scan was 69.54 HU (reader 2 = 69.01 HU) higher for F-NLB compared with conventional CECT. Also, the attenuation ratio between contrast-enhanced and pre-contrast CT data for the non-ischemic walls showed significantly higher values for the F-NLB image (CECT: reader 1 = 2.11 (reader 2 = 3.36), F-NLB: reader 1 = 4.46 (reader 2 = 4.98)]. Sensitivity in detecting ischemic areas increased significantly for both readers using F-NLB (CECT: reader 1/2 = 53%/65% versus F-NLB: reader 1/2 = 62%/75%). Frequency selective non-linear blending improves detection of bowel ischemia compared with conventional CECT by increasing

  7. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

    Directory of Open Access Journals (Sweden)

    Yuanjun Zhu

    Full Text Available Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB due to its large size. A protein transduction domain (PTD of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP, which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic

  8. Acute Neurological Symptoms During Hypobaric Exposure: Consider Cerebral Air Embolism

    NARCIS (Netherlands)

    Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

    2012-01-01

    WEENINK RP, HOLLMANN MW, VAN HULST RA. Acute neurological symptoms during hypobaric exposure: consider cerebral air embolism. Aviat Space Environ Med 2012; 83:1084-91. Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive medical procedures and as a risk in diving and

  9. Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

    2016-07-01

    The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

  10. Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

    Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

  11. Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Warfvinge, Karin; Scherfig, Erik

    2009-01-01

    The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure...... of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2h induced significant reductions in the amplitudes...... the ischemic insult. This model seems to be suitable for investigations of therapeutic initiatives in diseases involving acute retinal ischemia....

  12. Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Browning DJ

    2016-12-01

    Full Text Available David J Browning, Omar S Punjabi, Chong Lee Department of Ophthalmology, Charlotte Eye, Ear, Nose and Throat Associates, P.A., Charlotte, NC, USA Purpose: To determine the relationship between different spectral domain optical coherence tomography (SD-OCT signs of retinal ischemia in acute central retinal vein occlusion (CRVO and whether they predict anterior segment neovascularization (ASNV.Design: Retrospective, observational study.Subjects: Thirty-nine consecutive patients with acute CRVO and 12 months of follow-up.Methods: We graded baseline SD-OCTs for increased reflectivity of the inner retina, loss of definition of inner retinal layers, presence of a prominent middle-limiting membrane (p-MLM sign, and presence of paracentral acute middle maculopathy (PAMM. Graders were masked with respect to all clinical information.Results: The intraclass correlation coefficients (ICCs of grading–regrading by graders 1 and 2 were 0.8104, 95% confidence interval (CI (0.6686, 0.8956, and 0.7986, 95% CI (0.6475, 0.8892, respectively. The intragrader coefficients of repeatability (COR for graders 1 and 2 were 0.94 and 0.92, respectively. The ICC of graders 1 compared with 2 was 0.8039, 95% CI (0.6544, 0.8916. The intergrader COR was 0.80. SD-OCT grades of baseline ischemia were not associated with baseline visual acuity (VA, central subfield mean thickness (CSMT, or relative afferent pupillary defect; 12-month VA, CSMT, change in VA, change in CSMT, number of antivascular endothelial growth factor injections or corticosteroid injections, or proportion of eyes developing ASNV. SD-OCT grades of ischemia did not correlate with the proportion of eyes having the p-MLM sign or PAMM. PAMM and p-MLM are milder signs of ischemia than increased reflectivity of the inner retinal layers. Eyes with PAMM can evolve, losing PAMM and gaining the p-MLM sign.Conclusion: Grading of ischemia from SD-OCT in acute CRVO was repeatable within graders and reproducible across

  13. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

  14. Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

    Science.gov (United States)

    Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

    2012-01-01

    Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

  15. PI3K/Akt Pathway Contributes to Neurovascular Unit Protection of Xiao-Xu-Ming Decoction against Focal Cerebral Ischemia and Reperfusion Injury in Rats

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    Rui Lan

    2013-01-01

    Full Text Available In the present study, we used a focal cerebral ischemia and reperfusion rat model to investigate the protective effects of Xiao-Xu-Ming decoction (XXMD on neurovascular unit and to examine the role of PI3K (phosphatidylinositol 3-kinase/Akt pathway in this protection. The cerebral ischemia was induced by 90 min of middle cerebral artery occlusion. Cerebral infarct area was measured by tetrazolium staining, and neurological function was observed at 24 h after reperfusion. DNA fragmentation assay, combined with immunofluorescence, was performed to evaluate apoptosis of neuron, astrocyte, and vascular endothelial cell which constitute neurovascular unit. The expression levels of proteins involved in PI3K/Akt pathway were detected by Western blot. The results showed that XXMD improved neurological function, decreased cerebral infarct area and neuronal damage, and attenuated cellular apoptosis in neurovascular unit, while these effects were abolished by inhibition of PI3K/Akt with LY294002. We also found that XXMD upregulated p-PDKl, p-Akt, and p-GSK3β expression levels, which were partly reversed by LY294002. In addition, the increases of p-PTEN and p-c-Raf expression levels on which LY294002 had no effect were also observed in response to XXMD treatment. The data indicated the protective effects of XXMD on neurovascular unit partly through the activation of PI3K/Akt pathway.

  16. Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis.

    Science.gov (United States)

    Weinstein, J M; Bresnick, G H; Bell, C L; Roschmann, R A; Brooks, B R; Strother, C M

    1988-09-01

    Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity.

  17. MCP-1/CCR-2-double-deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice.

    Science.gov (United States)

    Schuette-Nuetgen, Katharina; Strecker, Jan-Kolja; Minnerup, Jens; Ringelstein, E Bernd; Schilling, Matthias

    2012-02-01

    Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR-2 are known to play a major role in inflammatory responses after cerebral ischemia. Mice deficient in either MCP-1 or CCR-2 have been reported to develop smaller infarct sizes and show decreased numbers of infiltrating inflammatory cells. In the present study we used green fluorescent protein (GFP) transgenic mice to investigate the effect of MCP-1/CCR-2-double deficiency on the recruitment of inflammatory cells in a model of both, mild and severe cerebral ischemia. We show that MCP-1/CCR-2-double deficiency virtually entirely abrogates the recruitment of hematogenous macrophages and significantly reduces neutrophil migration to the ischemic brain 4 and 7 days following focal cerebral ischemia. This argues for a predominant role of the MCP-1/CCR-2 axis in chemotaxis of monocytes despite a wide redundancy in the chemokine-receptor-system. Chemokine analysis revealed that even candidates known to be involved in monocyte and neutrophil recruitment like MIP-1α, CXCL-1, C5a, G-CSF and GM-CSF showed a reduced and delayed or even a lack of relevant compensatory response in MCP-1(-/-)/CCR-2(-/-)-mice. Solely, chemokine receptor 5 (CCR-5) increased early in both, but rose above wildtype levels at day 7 in MCP-1(-/-)/CCR-2(-/-)-animals, which might explain the higher number of activated microglial cells compared to control mice. Our study was, however, not powered to investigate infarct volumes. Further studies are needed to clarify whether these mechanisms of inflammatory cell recruitment might be essential for early infarct development and final infarct size and to evaluate potential therapeutic implications. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Comparison of cerebral blood flow and metabolism to flumazenil binding potential in patients with hemodynamic ischemia

    International Nuclear Information System (INIS)

    Yukawa, Hirotsugu; Ogasawara, Kuniaki

    2003-01-01

    Because benzodiazepine receptors (BZR) are abundant in the cortex, an accumulation of 11 C-flumazenil which selectively bind to BZR may be useful as markers of neuron density. The aims of this study were to clarify the relationship between neuron density and cerebral oxygen metabolism and to investigate the usefulness of 11 C-flumazenil PET for detecting misery perfusion. The subjects were 16 patients with either internal carotid or middle cerebral arterial occlusive disease who underwent PET. Regional cerebral blood flow (CBF), regional cerebral oxygen extraction fraction (OEF), regional cerebral metabolic rate for oxygen (CMRO 2 ) and regional cerebrovascular reserve capacity (CVRC) to acetazolamide were calculated. After CBF study, flumazenil binding potential was measured using the [ 11 C] flumazenil bolus injection method. Forty-eight regions of interests (ROIs) were obtained in 16 patients. Flumazenil binding potential was correlated to CMRO 2 (r=0.337, p=0.0069), but in 7 of 48 ROIs, CMRO 2 decreased, whereas flumazenil binding potential did not change. Seventeen of 29 ROIs with decreased CVRC showed high OEF and the remaining 12 showed normal OEF. Flumazenil binding potential in ROIs with normal OEF was significantly lower than in those with high OEF (p=0.0003). This study demonstrated that 11 C-flumazenil PET is useful for detecting misery perfusion in patients with hemodynamic ischemia. (author)

  19. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    Science.gov (United States)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  20. Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Li-jun Liang

    2016-01-01

    Full Text Available Up to now, over 1,000 experimental treatments found in cells and rodents have been difficult to translate to human ischemic stroke. Since ischemia and reperfusion, two separate stages of ischemic stroke, have different pathophysiological mechanisms leading to brain injury, a combination of protective agents targeting ischemia and reperfusion respectively may obtain substantially better results than a single agent. Normobaric hyperoxia (NBO has been shown to exhibit neuro- and vaso-protective effects by improving tissue oxygenation when it is given during ischemia, however the effect of NBO would diminish when the duration of ischemia and reperfusion was extended. Therefore, during reperfusion drug treatment targeting inflammation, oxidative stress and free radical scavenger would be a useful adjuvant to extend the therapeutic window of tissue plasminogen activator, the only United States Food and Drug Administration (FDA approved treatment for acute ischemic stroke. In this review, we discussed the neuro- and vaso-protective effects of NBO and recent finding of combining NBO with other drugs.

  1. [Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

    Science.gov (United States)

    Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

    2014-05-01

    To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (PsLocomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

  2. Deep Sequencing Reveals Uncharted Isoform Heterogeneity of the Protein-Coding Transcriptome in Cerebral Ischemia.

    Science.gov (United States)

    Bhattarai, Sunil; Aly, Ahmed; Garcia, Kristy; Ruiz, Diandra; Pontarelli, Fabrizio; Dharap, Ashutosh

    2018-06-03

    Gene expression in cerebral ischemia has been a subject of intense investigations for several years. Studies utilizing probe-based high-throughput methodologies such as microarrays have contributed significantly to our existing knowledge but lacked the capacity to dissect the transcriptome in detail. Genome-wide RNA-sequencing (RNA-seq) enables comprehensive examinations of transcriptomes for attributes such as strandedness, alternative splicing, alternative transcription start/stop sites, and sequence composition, thus providing a very detailed account of gene expression. Leveraging this capability, we conducted an in-depth, genome-wide evaluation of the protein-coding transcriptome of the adult mouse cortex after transient focal ischemia at 6, 12, or 24 h of reperfusion using RNA-seq. We identified a total of 1007 transcripts at 6 h, 1878 transcripts at 12 h, and 1618 transcripts at 24 h of reperfusion that were significantly altered as compared to sham controls. With isoform-level resolution, we identified 23 splice variants arising from 23 genes that were novel mRNA isoforms. For a subset of genes, we detected reperfusion time-point-dependent splice isoform switching, indicating an expression and/or functional switch for these genes. Finally, for 286 genes across all three reperfusion time-points, we discovered multiple, distinct, simultaneously expressed and differentially altered isoforms per gene that were generated via alternative transcription start/stop sites. Of these, 165 isoforms derived from 109 genes were novel mRNAs. Together, our data unravel the protein-coding transcriptome of the cerebral cortex at an unprecedented depth to provide several new insights into the flexibility and complexity of stroke-related gene transcription and transcript organization.

  3. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Directory of Open Access Journals (Sweden)

    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  4. Neuroimaging patterns of cerebral hyperperfusion

    Science.gov (United States)

    Semenov, S.; Portnov, Yu; Semenov, A.; Korotkevich, A.; Kokov, A.

    2017-08-01

    Cerebral hyperperfusion syndrome (CHS) after revascularization is a rare phenomenon associated with post-ischemic (reactive) hyperemia and acute pathological hyperperfusion. First described on perfusion CT as a very often moderate CBF increase, MTT/TTP decrease within 30% like a temporary effect, according to a short-time deterioration of neurological symptoms (vestibular ataxia - 58%, vegetative dysfunction - 100%, asthenic syndrome - 100%) in early postoperative period in patients with cardiac ischemia who had undergone coronary artery bypass surgery. The acute pathological hyperperfusion carotid revascularization is a casuistic phenomenon with two- or three-fold CBV and MTT/TTP increase and high hemorrhage risk. Besides, we detected similar exchanges via perfusion CT called benign hyperemia, which marks extension of MTT/TTP and an increase of CBV from 27% to 48% (average 30%), but with normal CBF-parameters, indicating that venous stasis in acute venous ischemic stroke due cerebral venous sinus-trombosis (68%), only 6% in cardioembolic stroke and appears never in arterial stroke. Territorial coincidence registered for perifocal of necrosis zones of benign hyperemia and vasogenic edema accompanied on MRI (DWI, ADC). Secondary hemorrhagic transformation registered for primary non-hemorrhagic venous stroke in 27%, only in 9% for arterial stroke and in 60% for cardioembolic stroke. Probably, congestion is an increasingly predisposing factor secondary hemorrhaging than necrosis.

  5. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Liu, Shimin; Shi, Honglian; Liu, Wenlan; Furuichi, Takamitsu; Timmins, Graham S; Liu, Ke Jian

    2004-03-01

    Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO2) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we measured both absolute values, and temporal changes of pO2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO2 to 32% +/- 7.6% and 4% +/- 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO2 close to its pre-ischemic value, penumbral pO2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO2 during ischemia, but not in the core, and also increased penumbral pO2 during reperfusion. These divergent, important changes in pO2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.

  6. Study on the change and relationship between plasma D-dimer and homocysteine levels in patients with acute cerebral vascular accident

    International Nuclear Information System (INIS)

    Lu Ye; Pan Xiangtao; Yan Min

    2009-01-01

    Objective: To study the clinical significance of the changes and the relationships between plasma D-dimer (D-D) and Homocysteine (Hcy) expression in patients with acute cerebral infarction and acute cerebral hemorrhage. Methods: Plasma D-D (with ELISA) and Hcy (with CLIA) levels were measured in 397 patients with cerebral infarction, 122 patients with cerebral hemorrhage and 30 controls.Results 1) The mean level of the plasma D-D and Hcy in patients with acute cerebral infarction was 5.20±0.92μg/L and 21.23±13.54 μmol/L respectively, which was significant higher than that in controls and patients with acute cerebral hemorrhage. 2) Higher expressing of D-D and Hcy was found in 101 (25.4%) and 140 (35.3%) cases of acute cerebral infarction patients. The data in acute cerebral hemorrhage group was 17 (13.9%) and 27 (22.1%) respectively. There was significant difference between two groups, P<0.01. 3) There was not correlations with the expression level of D-D and Hcy in patients with acute cerebral infarction and patients with acute cerebral hemorrhage. 4) The expressing level of the Plasma D-D in acute cerebral infarction patients was not significant difference in both age and sex. The expressing level of Hcy in male was higher than that in female. There was not significant difference in the expressing level of Hcy in different age. Conclusion: The levels of plasma D-D and Hcy in patients with acute cerebral infarction significantly in creased, but there were not correlations between the levels of the two parameters. (authors)

  7. The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats.

    Science.gov (United States)

    Uzar, Ertuğrul; Acar, Abdullah; Evliyaoğlu, Osman; Fırat, Uğur; Kamasak, Kağan; Göçmez, Cüneyt; Alp, Harun; Tüfek, Adnan; Taşdemir, Nebahat; Ilhan, Atilla

    2012-01-10

    The aim of this experiment was to investigate whether nebivolol and zofenopril have protective effects against oxidative damage and apoptosis induced by cerebral ischemia/reperfusion (I/R). There were seven groups of rats, with each containing eight rats. The groups were: the control group, I/R group, I/R plus zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril only and nebivolol only. Cerebral I/R was induced by clamping the bilateral common carotid artery and through hypotension. The rats were sacrificed 1h after ischemia, and histopathological and biochemical analyses were carried out on their brains. The total antioxidant capacity was evaluated by using an automated and colorimetric measurement method developed by Erel. I/R produced a significant increase in the levels of total oxidant status and malondialdehyde levels, the number of caspase-3 immunopositive cells and activities of prolidase and paraoxonase in brain when compared with the control group (ptotal antioxidant capacity and nitric oxide levels were found in I/R group when compared with the control group (ptotal antioxidant capacity and nitric oxide levels, produced by I/R in the brain (ptotal oxidant status, malondialdehyde levels, activities of paraoxonase and prolidase from increasing in brains of rats exposed to I/R (p<0.05). In conclusion, both nebivolol and zofenopril protected rats from ischemia-induced brain injury. The protection may be due to the indirect prevention of oxidative stress and apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

    Science.gov (United States)

    Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

    2015-04-01

    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

    OpenAIRE

    Wang, Peng-Fei; Xiong, Xiao-Yi; Chen, Jing; Wang, Yan-Chun; Duan, Wei; Yang, Qing-Wu

    2015-01-01

    Increasing evidence suggests that toll-like receptors (TLRs) play an important role in cerebral ischemia-reperfusion injury. The endogenous ligands released from ischemic neurons activate the TLR signaling pathway, resulting in the production of a large number of inflammatory cytokines, thereby causing secondary inflammation damage following cerebral ischemia. However, the preconditioning for minor cerebral ischemia or the preconditioning with TLR ligands can reduce cerebral ischemic injury b...

  10. Dengzhanhua preparations for acute cerebral infarction.

    Science.gov (United States)

    Cao, Wenzhai; Liu, Weimin; Wu, Taixiang; Zhong, Dechao; Liu, Guanjian

    2008-10-08

    Dengzhanhua preparations are widely used in China. Many controlled trials have been undertaken to investigate the efficacy of dengzhanhua preparations in the treatment of acute cerebral infarction. To assess whether dengzhanhua preparations are effective and safe at improving outcomes in patients with acute cerebral infarction. We searched the Cochrane Stroke Group Trials Register (last searched October 2007), the Chinese Stroke Trials Register (last searched June 2006), the trials register of the Cochrane Complementary Medicine Field (last searched June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), AMED (the Allied and Complementary Medicine Database, 1985 to June 2006), the China Biological Medicine Database (CBM-disc, 1979 to June 2006), and Chinese Knowledge Infrastructure (CNKI,1994 to October 2007). We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled clinical trials of dengzhanhua preparations regardless of duration, dosage and route of administration in patients with confirmed acute cerebral infarction. Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted the data. We included nine trials, all conducted in China, involving 723 participants. The method of randomisation and concealment was poorly described. The included trials compared dengzhanhua injection plus routine therapy with routine therapy alone. Patients were enrolled up to one week after the onset of stroke. No trials reported data on the pre-specified primary or secondary outcomes. In a post-hoc comparison of dengzhanhua injection plus routine therapy versus routine therapy alone, dengzhanhua injection showed a statistically significant benefit on the outcome 'marked neurologic improvement' (relative risk 1.53; 95% confidence interval 1.36 to 1.72). No serious adverse effects were

  11. Protective Effects of Sodium (±-5-Bromo-2-(α-Hydroxypentyl Benzoate in a Rodent Model of Global Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2017-09-01

    Full Text Available The aim of the current study was to explore the protective effects of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (brand name: brozopine, BZP in a rat model of global cerebral ischemia. The rat model was established using a modified Winocur’s method; close postoperative observation was conducted at all times. Neurological function was detected through prehensile traction and beam-walking test. BZP reduced mortality and prolonged the survival time of rats with global cerebral ischemia, within 24 h. There was a decreased survival rate (60% in the Model group, while the survival rate of the BZP (3 and 12 mg/kg remarkably increased the survival rate (to 80 and 90%, respectively, in a dose-dependent manner. Compared with the Model group (survival time: 18.50 h, the administration of BZP (0.75, 3, and 12 mg/kg prolonged the survival time (to 20.38, 21.85, and 23.90 h, respectively, particularly in BZP 12 mg/kg group (P < 0.05. Additionally, the BZP (12 mg/kg group exhibited an improvement in their motor function (P < 0.05. The BZP groups (0.75, 3, and 12 mg/kg displayed significantly reduced necrosis and the percentage of apoptotic cells (P < 0.05 and P < 0.01, respectively. Compared with Model group, BZP (0.75, 3, and 12 mg/kg increased the NeuN optical density values (P < 0.01. Rats with global ischemia had a high expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio compared with sham group (P < 0.01. BZP (0.75, 3, and 12 mg/kg, however, reduced the expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio, in a dose-dependent manner (P < 0.01. There was low expression of p-Akt and PI3K in Model group, compared with the sham group (P < 0.01. Meanwhile, BZP (0.75, 3, and 12 mg/kg increased the expression of p-Akt and PI3K in a dose-dependent manner (P < 0.01. We also found the expression of Cyt-c, caspase-3, Bax/Bcl-2 ratio, PI3K, p-Akt, and comprehensive score were directly related. In conclusion, BZP had therapeutic potential and prevented

  12. Cerebral lactate production and blood flow in acute stroke

    DEFF Research Database (Denmark)

    Henriksen, O; Gideon, P; Sperling, B

    1992-01-01

    that follows reperfusion. The amount of lactate present in the acute phase reflects the severity of ischemia in the affected region. The lactate level was still above normal in the subacute phase with hyperemia, suggesting lactate production through aerobic glycolysis. Thus, the lactate level in the subacute...... phase probably does not reflect the degree of anaerobic glycolysis in hypoxic neuronal tissue....

  13. Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.

    Science.gov (United States)

    Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Shirao, Satoshi; Suzuki, Michiyasu

    2011-01-01

    Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.

  14. Focal ischemia of the brain after neuroprotected carotid artery stenting.

    Science.gov (United States)

    Schlüter, Michael; Tübler, Thilo; Steffens, Johann C; Mathey, Detlef G; Schofer, Joachim

    2003-09-17

    This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.

  15. Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase

    International Nuclear Information System (INIS)

    Fung, A.Y.; Lai, P.; Juni, J.E.; Bourdillon, P.D.; Walton, J.A. Jr.; Laufer, N.; Buda, A.J.; Pitt, B.; O'Neill, W.W.

    1986-01-01

    To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction

  16. The evaluation of diffusion weighted imaging in acute cerebral infarction with permanent type MR scanner

    International Nuclear Information System (INIS)

    Peng Sen; Ye Wenwei; Luo Zhongrao; Yang Zenian; Zhang Zhongwei; Li Ziping

    2006-01-01

    Objective: To evaluate the value of diffusion weighted imaging (DWI) in acute cerebral infarction using permanent type MR scanner. Methods: DWI and conventional MRI sequences were done in 77 patients suspected with cerebral infarction. The sensitivity of DWI and conventional MRI was comparatively evaluated on lesion signal intensity and size. The characteristics and orderliness of lesions were studied. Results: (1) DWI has higher sensitivity than conventional MRI. (2) The higher b value was applied in the imaging, the higher signal intensity of acute cerebral infarction was revealed. The lesions were easier to identify on DWI images than on conventional MRI. Conclusion: DWI of permanent type MR imager is a feasible imaging modality, which is valuable in early diagnosis and management of acute cerebral infarction. (authors)

  17. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2017-11-01

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. © 2016 International Society of

  18. Cerebral blood flow in acute mountain sickness

    DEFF Research Database (Denmark)

    Jensen, J B; Wright, Anne; Lassen, N A

    1990-01-01

    Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased...

  19. The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

    Science.gov (United States)

    Oliff, H S; Marek, P; Miyazaki, B; Weber, E

    1996-08-26

    The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

  20. Intra-arterial thrombolysis using rt-PA in patients with acute stroke due to vessel occlusion of anterior and/or posterior cerebral circulation

    Energy Technology Data Exchange (ETDEWEB)

    Tountopoulou, Argyro; Ahl, Bjoern; Weissenborn, Karin [Hannover Medical School, Department of Neurology and Clinical Neurophysiology, Hannover (Germany); Becker, Hartmut; Goetz, Friedrich [Hannover Medical School, Department of Neuroradiology, Hannover (Germany)

    2008-01-15

    The aim of our study was to evaluate the safety and efficacy of intra-arterial (IA) thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute stroke due to occlusion in the anterior or posterior circulation. We retrospectively analyzed the clinical and radiological data of 88 consecutive patients with acute ischemic stroke who underwent emergency cerebral angiography for the purpose of subsequent IA thrombolysis. The neurological deficit on admission and discharge was graded using the National Institutes of Health Stroke Scale (NIHSS) score. Baseline computer tomography (CT) scans were examined for any signs indicative of cerebral ischemia. The angiographic findings were classified according to the Thrombolysis in Myocardial Infarction (TIMI) score for myocardial infarction. Follow-up CT scans were examined for hemorrhagic complication. Of the 88 patients who underwent IA thrombolysis, 63 presented with complete or partial arterial occlusion in the suspected perfusion area. In these 63 patients, the median NIHSS score dropped from 15 points on admission to 10 points at discharge. The recanalization rate was 52.6% for partial and complete reperfusion. In-hospital mortality was 20.6% (9.1% for carotid, 44.4% for basilar territory occlusion). Intracerebral bleeding (ICB) occurred in 38.6% of the patients with occlusion in the anterior circulation, resulting in these patients presenting a worse clinical outcome than those without ICB. Only minor extracranial bleedings occurred in 20.6% of patients. Patients with ICB had a significantly higher frequency of ischemic signs on the baseline CT scan. Occlusion of a cerebral artery is present in about 75% of the patients eligible for thrombolytic therapy. Intra-arterial thrombolysis using rt-PA in patients with acute ischemic stroke can achieve re-vascularization, although ICB remains the major risk factor affecting its efficacy. (orig.)

  1. Intra-arterial thrombolysis using rt-PA in patients with acute stroke due to vessel occlusion of anterior and/or posterior cerebral circulation

    International Nuclear Information System (INIS)

    Tountopoulou, Argyro; Ahl, Bjoern; Weissenborn, Karin; Becker, Hartmut; Goetz, Friedrich

    2008-01-01

    The aim of our study was to evaluate the safety and efficacy of intra-arterial (IA) thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute stroke due to occlusion in the anterior or posterior circulation. We retrospectively analyzed the clinical and radiological data of 88 consecutive patients with acute ischemic stroke who underwent emergency cerebral angiography for the purpose of subsequent IA thrombolysis. The neurological deficit on admission and discharge was graded using the National Institutes of Health Stroke Scale (NIHSS) score. Baseline computer tomography (CT) scans were examined for any signs indicative of cerebral ischemia. The angiographic findings were classified according to the Thrombolysis in Myocardial Infarction (TIMI) score for myocardial infarction. Follow-up CT scans were examined for hemorrhagic complication. Of the 88 patients who underwent IA thrombolysis, 63 presented with complete or partial arterial occlusion in the suspected perfusion area. In these 63 patients, the median NIHSS score dropped from 15 points on admission to 10 points at discharge. The recanalization rate was 52.6% for partial and complete reperfusion. In-hospital mortality was 20.6% (9.1% for carotid, 44.4% for basilar territory occlusion). Intracerebral bleeding (ICB) occurred in 38.6% of the patients with occlusion in the anterior circulation, resulting in these patients presenting a worse clinical outcome than those without ICB. Only minor extracranial bleedings occurred in 20.6% of patients. Patients with ICB had a significantly higher frequency of ischemic signs on the baseline CT scan. Occlusion of a cerebral artery is present in about 75% of the patients eligible for thrombolytic therapy. Intra-arterial thrombolysis using rt-PA in patients with acute ischemic stroke can achieve re-vascularization, although ICB remains the major risk factor affecting its efficacy. (orig.)

  2. Clinical significance of changes of plasma TNF-α and CRP levels in patients with acute cerebral infarction

    International Nuclear Information System (INIS)

    Liu Xiaoyang; Xiao Changqing; He Yunnan

    2006-01-01

    Objective: To investigate the clinical significance of the changes of serum TNF-α and CRP levels in patients with acute cerebral infarction. Methods: Serum TNF-α (with RIA) and CRP (with scatter velocity turbidimetry) levels were determined in 50 patients with acute cerebral infarction and 62 controls. Results: The serum levels of TNF-α and CRP in patients with acute cerebral infarction were significantly higher than those in controls (P <0.01). Moreover, the levels were positively correlated with the size of the infarction (P<0.05). Conclusion: Changes of serum TNF-α and CRP levels during acute stage of cerebral infarction were closely related the clinical progression of the disease process. (authors)

  3. Radial extracorporeal shock wave therapy improves cerebral blood flow and neurological function in a rat model of cerebral ischemia.

    Science.gov (United States)

    Kang, Nan; Zhang, Jing; Yu, Xiaotong; Ma, Yuewen

    2017-01-01

    We performed middle cerebral artery occlusion (MCAO) in rats to investigate the effect and some of the underlying mechanisms of radial extracorporeal shock wave therapy (rESWT) in cerebral ischemia rats. We measured neurological function and cerebral blood flow (CBF) using a full-field laser perfusion imager and brain infarct volume on days 3, 12, and 30. Immunofluorescence, western blot, and real-time polymerase chain reaction (PCR) techniques were used to detect the expression of vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), nestin, Wnt3a, and β-catenin in the ischemic hemisphere. The dose of rESWT used on the head revealed remarkable advantages over sham rESWT, as demonstrated by improved neurological function scores, increased CBF, and reduced brain infarct volume. Furthermore, applying rESWT to the head and limbs enhanced short-term neurological function. Our results confirmed that rESWT can induce VEGF expression over an extended period with a profound effect, which may be the primary reason for CBF recovery. High NSE and nestin expression levels suggest that rESWT enhanced the number of neurons and neural stem cells (NSCs). Wnt3a and β-catenin expression were up-regulated in the ischemic hemisphere, indicating that rESWT promoted NSC proliferation and differentiation via the Wnt/β-catenin pathway. Overall, our findings suggest that an appropriate rESWT dose delivered to the head of rats helps restore neurological function and CBF, and additional application of rESWT to the limbs is more effective than treating the head alone.

  4. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Kokubu, Yasuhiro; Yamaguchi, Tomoko; Kawabata, Kenji

    2017-04-29

    Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study. In the recent study, an induction method of BMECs from PSCs has been established, making it possible to more precisely study the in vitro human BBB function. Here, using induced pluripotent stem (iPS) cell-derived BMECs, we examined the effects of oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) on BBB permeability. OGD disrupted the barrier function, and the dysfunction was rapidly restored by re-supply of the oxygen and glucose. Interestingly, TNF-α, which is known to be secreted from astrocytes and microglia in the cerebral ischemia, prevented the restoration of OGD-induced barrier dysfunction in an apoptosis-independent manner. Thus, we could establish the in vitro BBB disease model that mimics the cerebral ischemia by using iPS cell-derived BMECs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Klotho upregulation contributes to the neuroprotection of ligustilide against cerebral ischemic injury in mice.

    Science.gov (United States)

    Long, Fang-Yi; Shi, Meng-Qi; Zhou, Hong-Jing; Liu, Dong-Ling; Sang, Na; Du, Jun-Rong

    2018-02-05

    Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms. Administration of ligustilide prevented the development of neurological deficits and reduced neuronal loss in the hippocampal CA1 region and the caudate putamen after cerebral ischemia. The protective effects were associated with inhibition of the RIG-I/NF-κB p65 and Akt/FoxO1 pathways and with prevention of inflammation and oxidative stress in the brain. Further, downregulation of klotho could attenuate the neuroprotection of ligustilide against cerebral ischemic injury. Ligustilide exerted neuroprotective effects in mice after cerebral ischemia by regulating anti-inflammatory and anti-oxidant signaling pathways. Furthermore, klotho upregulation contributes to the neuroprotection of LIG against cerebral ischemic injury. These results indicated that ligustilide may be a promising therapeutic agent for the treatment of cerebral ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Time Course of Changes in Extravascular Lung Water Index, Intracranial and Cerebral Perfusion Pressures in Acute Cerebral Circulatory Disorders

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2009-01-01

    Full Text Available Objective: to study the time course of changes in extravascular lung water index (ELWI and intracranial and cerebral perfusion pressures (ICP and CPP and to determine their possible relationships in acute cerebral circulatory disorders (ACCD. Subject and methods. ELWI, pulmonary vascular permeability index (PVPI, ICP, CPP, and central hemodynamics were studied by transpulmonary thermodilution and current X-ray studies were conducted in 18 patients on days 1, 3, 5, and 7 of ACCD. Results. Examinations revealed a supratentorial dislocation of the brain in 6 persons; its subtento-rial dislocation was found in 1 case; supra- and subtentorial dislocations were seen in 6. In patients, ELWI and PVPI increased from days 1 and 5, respectively. The high baseline ICP increased over time. CPP remained unchanged. Preserved left ventricular contractility, enhanced myocardial one, a significant direct correlation between ELWI and PVPI, as well as their increase confirmed that the noncardiogenic genesis was responsible for increased ELWI. A direct significant correlation was found between ICP and ELWI, ICP and PVPI. Against this background, acute respiratory distress syndrome developed in 14 patients with pneumonia evolving in its presence in 7 patients. Conclusion. In ACCD, ELWI increases in the first 24 hours of the acute period. One of its causes is, along with others, primary and/or secondary damage to the brainstem structures with elevated ICP and progressive brain dislocation. The determination of ICP, unlike CPP, is crucial in the diagnosis and treatment of primary/secondary brain injuries and in prognosis. Key words: acute cerebral circulatory disorder, extravascular lung fluid, pulmonary vascular permeability, intracranial pressure, cerebral perfusion pressure, acute respiratory distress syndrome.

  7. Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma

    International Nuclear Information System (INIS)

    Huisman, Thierry A.G.M.

    2003-01-01

    Diffusion-weighted imaging (DWI) of the brain represents a new imaging technique that extends imaging from depiction of neuroanatomy to the level of function and physiology. DWI measures a fundamentally different physiological parameter compared with conventional MRI. Image contrast is related to differences in the diffusion rate of water molecules rather than to changes in total tissue water. DWI can reveal pathology in cases where conventional MRI remains unremarkable. DWI has proven to be highly sensitive in the early detection of acute cerebral ischemia and seems promising in the evaluation of traumatic brain injury. DWI can differentiate between lesions with decreased and increased diffusion. In addition, full-tensor DWI can evaluate the microscopic architecture of the brain, in particular white matter tracts, by measuring the degree and spatial distribution of anisotropic diffusion within the brain. This article reviews the basic concepts of DWI and its application in cerebral ischemia and traumatic brain injury. (orig.)

  8. Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma

    Energy Technology Data Exchange (ETDEWEB)

    Huisman, Thierry A.G.M. [Department of Radiology, Neuroradiology Section and MGH-NMR Center, Massachusetts General Hospital and Harvard Medical School, MA 02129, Boston (United States); Department of Radiology, University Children' s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich (Switzerland)

    2003-10-01

    Diffusion-weighted imaging (DWI) of the brain represents a new imaging technique that extends imaging from depiction of neuroanatomy to the level of function and physiology. DWI measures a fundamentally different physiological parameter compared with conventional MRI. Image contrast is related to differences in the diffusion rate of water molecules rather than to changes in total tissue water. DWI can reveal pathology in cases where conventional MRI remains unremarkable. DWI has proven to be highly sensitive in the early detection of acute cerebral ischemia and seems promising in the evaluation of traumatic brain injury. DWI can differentiate between lesions with decreased and increased diffusion. In addition, full-tensor DWI can evaluate the microscopic architecture of the brain, in particular white matter tracts, by measuring the degree and spatial distribution of anisotropic diffusion within the brain. This article reviews the basic concepts of DWI and its application in cerebral ischemia and traumatic brain injury. (orig.)

  9. Effect of electroacupuncture on brain-derived neurotrophic factor mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Jianxin; Xu, Huazhou; Tian, Yuanxiang; Hu, Manxiang; Xiao, Hongling

    2013-04-01

    This work aims to observe the effects of electroacupuncture on brain-derived neurotrophic factor (BDNF) mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury. The models of mouse cerebral ischemia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, model + electroacupuncture, and mode + hydergine groups. Mice in the model + electroacupuncture group were treated through electroacupuncture at the Shenshu (BL 23), Geshu (BL 17), and Baihui (GV 20) acupoints. Mice in the model+hydergine group were intragastrically administered with hydergine (0.77 mg/kg(-1) x day(-1)). The levels of BDNF mRNA expressions in the hippocampus were ana lyzed through a semi-quantitative reverse transcription-polymerase chain reaction assay on days 1 and 7 after the surgeries. BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group (both P electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the model + electroacupuncture group was significantly elevated compared with the model group (both P 0.05). Electroacupuncture treatment enhances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.

  10. Bexarotene reduces blood-brain barrier permeability in cerebral ischemia-reperfusion injured rats.

    Directory of Open Access Journals (Sweden)

    Lu Xu

    Full Text Available Matrix metalloproteinase-9 (MMP-9 over-expression disrupts the blood-brain barrier (BBB in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction.A total of 180 rats were randomized into three groups (n = 60 each: (i a sham-operation group, (ii a cerebral ischemia-reperfusion (I/R group, and (iii an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE, claudin-5, and occludin expression were analyzed by Western blotting.After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i brain water content and BBB permeability were significantly reduced; (ii MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii claudin-5 and occludin expression were significantly increased; and (iv apoE expression was significantly increased.Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene's upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients.

  11. Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies Proposal of a Multidisciplinary Research Group

    NARCIS (Netherlands)

    Vergouwen, Mervyn D. I.; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J. E.; Wijdicks, Eelco F.; Muizelaar, J. Paul; Mendelow, A. David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G.; Macdonald, R. Loch; Diringer, Michael N.; Broderick, Joseph P.; Dreier, Jens P.; Roos, Yvo B. W. E. M.

    2010-01-01

    Background and Purpose-In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of

  12. Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor

    Directory of Open Access Journals (Sweden)

    Ming-Shu Xu

    2013-01-01

    Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

  13. Effects of Electroacupuncture Combined with Repetitive Transcranial Magnetic Stimulation on the Expression of Nestin in Neural Stem Cell after Focal Cerebral Ischemia in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Guofu; HUANG Xiaolin; CHEN Hong; HAY Xiaohua

    2009-01-01

    Objective: To investigate the influence of electroacupuncture (EA) combined with repetitive transeranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral isehemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury. Method: The model of transient focal ischemia was produced by occlusion of middle cerebral artery. Seventy-five Wistar rats were randomly divided into normal group, model group, EA group, rTMS group and EA +rTMS group. The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively. Meanwhile, Western blotting was used to observe the number of nestin expression positive cells. Result: Nestin-positive cells were found in cortex, subgranular zone (SGZ), subventricular zone (SVZ) of the ipsilateral side at different time points after cerebral isehemia. The number of nestin-positive cells peaked at the 7th d, began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group (P<0.05), then almost reached normal at the 28th d. The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group (P<0.01, P<0.05). These effects were most obvious in EA+rTMS group compared with the EA and rTMS group (P<0.05). Conclusion: EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia, which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.

  14. Intra-artery thrombolytic therapy for acute ischemic cerebral infarction

    International Nuclear Information System (INIS)

    Du Wei; Shao Chengmin; Wang Jianlin; Lei Jin; Jia Fan; Cao Lanfang; Chai Ruchang; Su Wei; Gu Jinchuan

    2004-01-01

    Objective: To evaluate the clinical effects of intra-arterial thrombolytic therapy for acute ischemic cerebral infarction and analyze the factors influencing the clinical prognosis. Methods: 32 patients were treated with intra-arterial thrombolysis using urokinase (median dose, 65 x 10 4 U) within 2-20 hours, after the onset. The patient's condition was assessed by neurologists using National Institutes of Health Stroke Scale (NIHSS) score right at the admission. Clinical outcome was assessed after 3 months and graded as good for Modified Rankin Scale (MRS) scores of 0 to 3 and poor for MRS scores of 4 or 5 and death. Results: Follow up cerebral angiography of 14 cases treated within 6 hours after onset showed complete/partial recanalization in 13 cases. Other 18 patients whose treatment started beyond 6 hours after onset out-came with complete/partial in 7. 20 (62.5%) of the 32 patients had good out-come, 12(37.5%) had poor outcome and two patients(9.4%) died. Cerebral hemorrhage occurred in 2 of the 32 patients. Good outcome was associated with an initial NIHSS score of <20 (P<0.01) and vascular recanalization (P<0.025). Recanalization was more likely to be obtained if thrombolysis began within 6 hours (P<0.05). Conclusion: Intra-arterial thrombolysis is a safe and effective therapy for acute ischemic cerebral infarction. (authors)

  15. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

    Science.gov (United States)

    Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

    2017-10-01

    Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

  16. Contrast enhancement pattern in MR imaging of acute cerebral infarction

    International Nuclear Information System (INIS)

    Kim, Jong Deok; Cho, Mee Young; Lee, Chae Guk; Song, Dong Hoon

    1994-01-01

    To present the enhancement pattern of acute cerebral or cerebellar cortical infarctions aged 1-3 days on MR. Contrast-enhanced MR images of 26 patients with acute cerebral or cerebellar ischemic events were retrospectively reviewed. MR was performed within 3 days after ictus. Contrast enhancement in the area of infarction was observed in 61.5% (16/26) on MR. Of these 50% (13/26) showed non-parenchymal enhancement (NPE) representing either vascular or leptomeningeal enhancement, 7.7% (2/26) showed parenchymal enhancement (PE), and 2.8% (1/26) showed both NPE and PE. The earliest enhancement was seen in images obtained 12 hours after the onset of symptoms and appeared as NPE. One patient showed NPE without apparent high signal intensity at the corresponding area on T2-weighted images. In 38.5% (10/26), there was no enhancement. Contrast-enhanced MR imaging may be needed in acute ischemic infarction, because NPE may be seen as the earliest MR finding of acute cortical infraction aged 1-3 days

  17. Contrast enhancement pattern in MR imaging of acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Deok; Cho, Mee Young; Lee, Chae Guk; Song, Dong Hoon [Inje University College of Medicine, Pusan (Korea, Republic of)

    1994-08-15

    To present the enhancement pattern of acute cerebral or cerebellar cortical infarctions aged 1-3 days on MR. Contrast-enhanced MR images of 26 patients with acute cerebral or cerebellar ischemic events were retrospectively reviewed. MR was performed within 3 days after ictus. Contrast enhancement in the area of infarction was observed in 61.5% (16/26) on MR. Of these 50% (13/26) showed non-parenchymal enhancement (NPE) representing either vascular or leptomeningeal enhancement, 7.7% (2/26) showed parenchymal enhancement (PE), and 2.8% (1/26) showed both NPE and PE. The earliest enhancement was seen in images obtained 12 hours after the onset of symptoms and appeared as NPE. One patient showed NPE without apparent high signal intensity at the corresponding area on T2-weighted images. In 38.5% (10/26), there was no enhancement. Contrast-enhanced MR imaging may be needed in acute ischemic infarction, because NPE may be seen as the earliest MR finding of acute cortical infraction aged 1-3 days.

  18. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    DEFF Research Database (Denmark)

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon

    2006-01-01

    and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate......In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...... that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions...

  19. The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats.

    Science.gov (United States)

    Oruc, Serdar; Gönül, Yücel; Tunay, Kamil; Oruc, Oya Akpinar; Bozkurt, Mehmet Fatih; Karavelioğlu, Ergün; Bağcıoğlu, Erman; Coşkun, Kerem Senol; Celik, Sefa

    2016-06-01

    Cerebral ischemia reperfusion (IR) injury is a process in which oxidative and apoptotic mechanisms play a part. Neuroprotective agents to be found could work out well for the efficient and safe minimization of cerebral IR injury. Crocin is a strong antioxidant agent; however the influence of this agent on the experimental cerebral ischemia model has not been studied extensively and thus it is not well-known. The objective of our study was to investigate the antioxidant, antiapoptotic and protective effects of crocin on the global cerebral IR induced by four-vessel occlusion. A total of 30 adult female Sprague-Dawley rats were equally and randomly separated into three groups as follows: sham, IR and IR+crocin (40mg/kg/day orally for 10days). 24h after electrocauterization of bilateral vertebral arteries, bilateral common carotid arteries were occluded for 30min and reperfused for 30min. Oxidative stress parameters (TAS, TOS, OSI), haematoxylin and eosin staining, caspase-3 and hypoxia-inducible factor-1 alpha (HIF-1α) expressions and TUNEL methods were investigated. There was a significant difference between the IR and sham groups by means of OSI level, histopathological scoring, caspase-3, HIF-1α and TUNEL-positive cell parameters. We have also observed that pre-treatment with crocin reduced these parameter levels back to the baseline. The data obtained from the present study suggest that crocin may exert antiapoptotic, antioxidant and protective effects in IR-mediated brain injury induced by four-vessel occlusion. To the best of our knowledge, this would be the first study to be conducted in this field. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Study of the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Gui-Fa Chen

    2017-06-01

    Full Text Available Objective: To study the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats. Methods: SD rats were selected as experimental animals and divided into control group, model group, ticagrelor group and clopidogrel group, cerebral ischemic reperfusion injury models were made, then ticagrelor group were given intragastric administration of 150 mg ticagrelor, clopidogrel group were given intragastric administration of 90 mg clopidogrel. 1 week after intervention, the brain water content as well as the contents of oxidative stress molecules and inflammatory factors were measured. Results: Water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of model group were significantly higher than those of control group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly lower than those of control group; water content in brain, MDA, Ox-LDL, NFkB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group and clopidogrel group were significantly lower than those of model group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly higher than those of model group; water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group were significantly lower than those of clopidogrel group while SOD, GSHPx and Prdx6 contents in brain tissue were significantly higher than those of clopidogrel group. Conclusion: Ticagrelor can be more effective in inhibiting oxidative stress response and inflammatory response, and reducing the cerebral ischemia reperfusion injury than clopidogrel.

  1. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    Science.gov (United States)

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  2. Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3β pathway in rats.

    Science.gov (United States)

    Chen, Lin; Wei, Xinbing; Hou, Yunfeng; Liu, Xiaoqian; Li, Senpeng; Sun, Baozhu; Liu, Xinyong; Liu, Huiqing

    2014-01-01

    CXC195 showed strongest protective effects among the ligustrazine derivatives in cells and prevented apoptosis induced by H2O2 injury. We recently demonstrated that CXC195 protected against cerebral ischemia/reperfusion (I/R) injury by its antioxidant activity. However, whether the anti-apoptotic action of CXC195 is involved in cerebral I/R injury is unknown. Here, we investigated the role of CXC195 in apoptotic processes induced by cerebral I/R and the possible signaling pathways. Male Wistar rats were submitted to transient middle cerebral artery occlusion for 2h, followed by 24h reperfusion. CXC195 was injected intraperitoneally at 2h and 12h after the onset of ischemia. The number of apoptotic cells was measured by TUNEL assay, apoptosis-related protein cleaved caspase-3, Bcl-2, Bax and the phosphorylation levels of Akt and GSK3β in ischemic penumbra were assayed by western blot. The results showed that administration of CXC195 at the doses of 3mg/kg and 10mg/kg significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the level of cleaved caspase-3 and Bax, and increasing the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, CXC195 treatment markedly increased the phosphorylation of Akt and GSK3β. Blockade of PI3K activity by wortmannin, dramatically abolished its anti-apoptotic effect and lowered both Akt and GSK3β phosphorylation levels. Our study firstly demonstrated that CXC195 protected against cerebral I/R injury by reducing apoptosis in vivo and PI3K/Akt/GSK3β pathway involved in the anti-apoptotic effect. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  3. Functional and structural correlates of magnetic resonance patterns in a new in vitro model of cerebral ischemia by transient occlusion of the medial cerebral artery.

    Science.gov (United States)

    Breschi, Gian Luca; Librizzi, Laura; Pastori, Chiara; Zucca, Ileana; Mastropietro, Alfonso; Cattalini, Alessandro; de Curtis, Marco

    2010-08-01

    Magnetic resonance imaging (MRI) during the acute phase of a stroke contributes to recognize ischemic regions and is potentially useful to predict clinical outcome. Yet, the functional significance of early MRI alterations during brain ischemia is not clearly understood. We achieved an experimental study to interpret MRI signals in a novel model of focal ischemia in the in vitro isolated guinea pig brain. By combining neurophysiological and morphological analysis with MR-imaging, we evaluated the suitability of MR to identify ischemic and peri-ischemic regions. Extracellular recordings demonstrated depolarizations in the ischemic core, but not in adjacent areas, where evoked activity was preserved and brief peri-infarct depolarizations occurred. Diffusion-weighted MRI and immunostaining performed after neurophysiological characterization showed changes restricted to the core region. Diffusion-weighted MR alterations did not include the penumbra region characterized by peri-infarct depolarizations. Therefore, by comparing neurophysiological, imaging and anatomical data, we can conclude that DW-MRI underestimates the extension of the tissue damage involved in brain ischemia.

  4. HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

    Science.gov (United States)

    Gathier, C S; van den Bergh, W M; Slooter, A J C

    2014-04-01

    Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

  5. Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Tao-Jie Ren

    Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

  6. Regional cerebral blood flow and metabolism in patients with transient global amnesia. A study using SPECT and 1H-MRS

    International Nuclear Information System (INIS)

    Ishihara, Tetsuya; Hirata, Koichi; Tatsumoto, Muneto; Yamazaki, Kaoru; Sato, Toshihiko.

    1997-01-01

    In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT. MRI, and proton MR spectroscopy ( 1 H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using 1 H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of 1 H-MRS. These data suggest that TGA may not necessarily be caused by cerebra1 ischemia. (author)

  7. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

    Science.gov (United States)

    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural

  8. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

    International Nuclear Information System (INIS)

    Zhang, Shao-jie; Ke, Zheng; Tong, Kai-yu; Li, Le; Yip, Shea-ping

    2013-01-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  9. Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats

    Science.gov (United States)

    Zhu, Haiying; Fan, Yanxia; Sun, Hongyu; Chen, Liyan; Man, Xiao

    2017-01-01

    The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats. PMID:29067098

  10. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

    Science.gov (United States)

    Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

    2009-01-01

    One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

  11. Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten

    2000-01-01

    BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients...... with acute bacterial meningitis. METHODS: Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V...... completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (Pmeningitis, indicating...

  12. Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

    Directory of Open Access Journals (Sweden)

    Xianhua Zhang

    2017-07-01

    Full Text Available Previously, we only apply a traditional Chinese medicine (TCM Danshen-Chuanxiong-Honghua (DCH for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO. We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS, we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg and FA (100 mg/kg improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

  13. Acute stroke magnetic resonance imaging: current status and future perspective

    International Nuclear Information System (INIS)

    Kloska, Stephan P.; Wintermark, Max; Engelhorn, Tobias; Fiebach, Jochen B.

    2010-01-01

    Cerebral stroke is one of the most frequent causes of permanent disability or death in the western world and a major burden in healthcare system. The major portion is caused by acute ischemia due to cerebral artery occlusion by a clot. The minority of strokes is related to intracerebral hemorrhage or other sources. To limit the permanent disability in ischemic stroke patients resulting from irreversible infarction of ischemic brain tissue, major efforts were made in the last decade. To extend the time window for thrombolysis, which is the only approved therapy, several imaging parameters in computed tomography and magnetic resonance imaging (MRI) have been investigated. However, the current guidelines neglect the fact that the portion of potentially salvageable ischemic tissue (penumbra) is not dependent on the time window but the individual collateral blood flow. Within the last years, the differentiation of infarct core and penumbra with MRI using diffusion-weighted images (DWI) and perfusion imaging (PI) with parameter maps was established. Current trials transform these technical advances to a redefined patient selection based on physiological parameters determined by MRI. This review article presents the current status of MRI for acute stroke imaging. A special focus is the ischemic stroke. In dependence on the pathophysiology of cerebral ischemia, the basic principle and diagnostic value of different MRI sequences are illustrated. MRI techniques for imaging of the main differential diagnoses of ischemic stroke are mentioned. Moreover, perspectives of MRI for imaging-based acute stroke treatment as well as monitoring of restorative stroke therapy from recent trials are discussed. (orig.)

  14. Cerebral blood flow in acute and chronic ischemic stroke using xenon-133 inhalation tomography

    DEFF Research Database (Denmark)

    Vorstrup, S; Paulson, O B; Lassen, N A

    1986-01-01

    . They showed in the acute phase (Days 1-3) very large low-flow areas, larger than the hypodense areas seen on the CT scan. The cerebral vasoconstrictor and vasodilator capacity was tested in the acute phase following aminophylline and acetazolamide, respectively. A preserved but reduced reactivity was seen......Serial measurements of cerebral blood flow (CBF) were performed in 12 patients with acute symptoms of ischemic cerebrovascular disease. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. Six patients had severe strokes and large infarcts on the CT scan...

  15. Effect of Acute Resistance Exercise on Carotid Artery Stiffness and Cerebral Blood Flow Pulsatility

    Directory of Open Access Journals (Sweden)

    Wesley K Lefferts

    2014-03-01

    Full Text Available Arterial stiffness is associated with cerebral flow pulsatility. Arterial stiffness increases following acute resistance exercise (RE. Whether this acute RE-induced vascular stiffening affects cerebral pulsatility remains unknown. Purpose: To investigate the effects of acute RE on common carotid artery (CCA stiffness and cerebral blood flow velocity (CBFv pulsatility. Methods: Eighteen healthy men (22 ± 1 yr; 23.7 ± 0.5 kg∙m-2 underwent acute RE (5 sets, 5-RM bench press, 5 sets 10-RM bicep curls with 90 s rest intervals or a time control condition (seated rest in a randomized order. CCA stiffness (β-stiffness, Elastic Modulus (Ep and hemodynamics (pulsatility index, forward wave intensity and reflected wave intensity were assessed using a combination of Doppler ultrasound, wave intensity analysis and applanation tonometry at baseline and 3 times post-RE. CBFv pulsatility index was measured with transcranial Doppler at the middle cerebral artery (MCA. Results: CCA β-stiffness, Ep and CCA pulse pressure significantly increased post-RE and remained elevated throughout post-testing (p 0.05. There were significant increases in forward wave intensity post-RE (p0.05. Conclusion: Although acute RE increases CCA stiffness and pressure pulsatility, it may not affect CCA or MCA flow pulsatility. Increases in pressure pulsatility may be due to increased forward wave intensity and not pressure from wave reflections.

  16. Studies on asymptomatic cerebral ischemia in coronary heart disease with special reference to evaluation of postural changes in cerebral blood flow with {sup 99m}Tc-ECD brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Sinozaki, Hideko [Teikyo Univ., Tokyo (Japan). Faculty of Medicine

    2001-03-01

    Postural changes in cerebral blood flow in patients with coronary heart disease (CHD) were evaluated with SPECT to detect asymptomaic cerebral ischemia (ACI). {sup 99m}Tc-ECD was used as a tracer. We developed a new analysis system for the processing of multiple images, making it possible to avoid the spatial shift in ROIs in different positions. The severity of ACI was classified into 3 groups based on SPECT findings in the supine position: group 1 without any abnormalities in cerebral perfusion, group 2 with a single perfusion defect, and group 3 with a number of perfusion defects. No cerebral siteobserved in any group showed a significant difference between the supine and upright positions in cerebral perfusion. Each group in each position, however, revealed a consistent perfusion pattern characterized by a significant decrease in perfusion in the occipital, temporal and frontal lobes. Moreover, the decrease in the latter two sites was significantly greater than in the former site. Concerning clinical profiles, hypertension and the thickness of the intima and media complex (TIMC) of the common carotid artery significantly correlated with the severity of ACI. Furthermore, in multiple regression analysis, only TIMC was identified as a significant determinant of ACI. In conclusion, cerebral blood flow determined with {sup 99m}Tc-ECD SPECT could accurately detect ACI in patients with CHD. (author)

  17. Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage

    DEFF Research Database (Denmark)

    Schlader, Zachary J; Seifert, Thomas; Wilson, Thad E

    2013-01-01

    Hyperthermia reduces the capacity to withstand a simulated hemorrhagic challenge, but volume loading preserves this capacity. This study tested the hypotheses that acute volume expansion during hyperthermia increases cerebral perfusion and attenuates reductions in cerebral perfusion during...... infusion while hyperthermic. Primary dependent variables were mean middle cerebral artery blood velocity (MCAvmean), serving as an index of cerebral perfusion; mean arterial pressure (MAP); and cardiac output (thermodilution). During baseline, hyperthermia reduced MCAvmean (P = 0.001) by 12 ± 9% relative...

  18. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

    Science.gov (United States)

    Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

    2013-01-01

    Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

  19. Clinical significance of changes of serum Hcy and IGF-I levels after treatment in patients with acute cerebral infarction

    International Nuclear Information System (INIS)

    Wang Yuezhou

    2011-01-01

    Objective: To investigate the clinical significance of serum Hcy and IGF-I levels in patients with acute cerebral infarction. Methods: Serum IGF-I (with RIA), Hcy (with ELISA)levels were measured in 32 patients with acute cerebral infarction both before and after treatment as well as in 35 normal controls. Results: Before treatment, the serum Hcy level was remarkably higher than that in controls (P 0.05). Conclusion: The level of Hcy increased and IGF-I decreased in the patients with acute cerebral infarction which closely to the severity of acute cerebral infarction and may be taken as a sensitive biochemical indicator for predicting pathogenesis and progress of ACI. (authors)

  20. Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

    Science.gov (United States)

    Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

    2016-10-01

    Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Regional cerebral blood flow and metabolism in patients with transient global amnesia. A study using SPECT and {sup 1}H-MRS

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Tetsuya; Hirata, Koichi; Tatsumoto, Muneto; Yamazaki, Kaoru [Dokkyo Univ., Tochigi (Japan). School of Medicine; Sato, Toshihiko

    1997-06-01

    In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT. MRI, and proton MR spectroscopy ({sup 1}H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using {sup 1}H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of {sup 1}H-MRS. These data suggest that TGA may not necessarily be caused by cerebra1 ischemia. (author)

  2. Curative effect of monosialotetrahexosylganglioside combined with Xingnaojing injection on acute cerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Rui-xing SUN

    2015-07-01

    Full Text Available This paper aims to observe the curative effect of monosialotetrahexosylganglioside combined with Xingnaojing injection on acute cerebral hemorrhage. A total of 120 cases with acute cerebral hemorrhage were treated with Xingnaojing injection monotherapy (control group, N = 60 or monosialotetrahexosylganglioside combined with Xingnaojing injection (combined treatment group, N = 60. Bleeding amount and National Institutes of Health Stroke Scale (NIHSS scores of 2 groups were both significantly reduced on the 21th day after treatment (P = 0.000, for all, but bleeding amount and NIHSS scores in combined treatment group were significantly lower than those in control group (P = 0.000, for all. After 21 d treatment, total effective rate of combined treatment group was 86.67% (52/60, which was significantly higher than that of control group [66.67% (40/60; χ2 = 1.493, P = 0.024]. For patients with acute cerebral hemorrhage, monosialotetrahexosylganglioside combined with Xingnaojing injection can significantly improve the neurological function. DOI: 10.3969/j.issn.1672-6731.2015.07.014

  3. Prognosis after cerebral ischaemia of arterial origin: clinical characteristics and genetic information

    NARCIS (Netherlands)

    Achterberg, S.

    2013-01-01

    Background. Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, addition of genetic information might

  4. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  5. Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase

    Science.gov (United States)

    Huang, Zhihong; Huang, Paul L.; Panahian, Nariman; Dalkara, Turgay; Fishman, Mark C.; Moskowitz, Michael A.

    1994-09-01

    The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middl