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Ischemic Damage (ischemic + damage)
Selected AbstractsApraxia related with subcortical lesions due to cerebrovascular diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010N. E. Tabaki Tabaki NE, Vikelis M, Besmertis L, Vemmos K, Stathis P, Mitsikostas DD. Apraxia related with subcortical lesions due to cerebrovascular disease. Acta Neurol Scand: 2010: 122: 9,14. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To examine whether ideomotor apraxia exists in patients with subcortical ischemic lesions. Patients and Methods,,, A matched-control, prospective and multi-centered research design was used. Ideomotor apraxia, anxiety and depression were assessed by the Movement Imitation Test and the Hamilton scales, respectively. Results,,, Forty two consecutive patients with subcortical ischemic stroke and an equal number of healthy participants, matched in age and sex were included. Paired-sample t-tests showed that patients had significantly more apractic elements in their movements (t = 5.03, P < 0.01), higher anxiety (t = ,2.55, P = 0.0014) and depression levels (t = ,2.61, P = 0.012) than their healthy matched participants. Participants with higher anxiety and depression scores performed worse on the Movement Imitation Test. Conclusions,,, Ischemic damage of subcortical modular systems may affect praxis. [source] Simultaneous management of blood flow and IOP in glaucomaACTA OPHTHALMOLOGICA, Issue 4 2001Alon Harris ABSTRACT. Factors other than intraocular pressure (IOP) elevation must be involved in initiation and progression of glaucoma. An additional element in disease causation may be ischemia in the retina and optic nerve head. Ischemic damage to neurons in the CNS is similar mechanistically and histopathologically to changes seen in glaucoma. Further, glaucoma patients with normal IOP show clear evidence for cerebral and ocular ischemia. Aging and atherosclerosis reduce the ability of the eye to autoregulate blood flow when ocular perfusion pressure changes: the dependence of blood flow on perfusion pressure links ischemia to IOP. Consequently, neuroprotective treatments for glaucoma should be designed to both reduce IOP and improve ocular nutrient delivery. [source] Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in miceAGING CELL, Issue 1 2010James R. Mitchell Summary Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2,4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals. [source] Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in miceAGING CELL, Issue 2 2009Denis Susa Summary Cockayne syndrome and other segmental progerias with inborn defects in DNA repair mechanisms are thought to be due in part to hypersensitivity to endogenous oxidative DNA damage. The accelerated aging-like symptoms of this disorder include dysmyelination within the central nervous system, progressive sensineuronal hearing loss and retinal degeneration. We tested the effects of congenital nucleotide excision DNA repair deficiency on acute oxidative stress sensitivity in vivo. Surprisingly, we found mouse models of Cockayne syndrome less susceptible than wild type animals to surgically induced renal ischemia reperfusion injury, a multifactorial injury mediated in part by oxidative damage. Renal failure-related mortality was significantly reduced in Csb,/, mice, kidney function was improved and proliferation was significantly higher in the regenerative phase following ischemic injury. Protection from ischemic damage correlated with improved baseline glucose tolerance and insulin sensitivity and a reduced inflammatory response following injury. Protection was further associated with genetic ablation of a different Cockayne syndrome-associated gene, Csa. Our data provide the first functional in vivo evidence that congenital DNA repair deficiency can induce protection from acute stress in at least one organ. This suggests that while specific types of unrepaired endogenous DNA damage may lead to detrimental effects in certain tissues, they may at the same time elicit beneficial adaptive changes in others and thus contribute to the tissue specificity of disease symptoms. [source] Time evolution of cerebral perfusion and apparent diffusion coefficient measured by magnetic resonance imaging in a porcine stroke modelJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2002Lisbeth Røhl MD Abstract Purpose To demonstrate the feasibility of sequential diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance imaging (MRI) of a recently developed porcine stroke model and to evaluate the evolution of cerebral perfusion and the apparent diffusion coefficient (ADC) over time. Materials and Methods In five pigs, DW imaging (DWI) and PW imaging (PWI) was carried out for 7 hours after stroke onset, starting 1 hour after middle cerebral artery occlusion (MCAO). Results The DWI lesion volume increased significantly with time, and final DWI lesion volume correlated well with lesion area on histological sections (r = 0.910). T2 changes could be recognized 3 hours after stroke onset. At 1 hour the ADC ratio (ischemic lesion/contralateral side) was reduced to 0.81 in the caudate-putamen and to 0.87 in the cortex, and the cerebral blood flow ratio was reduced to 0.40 in the caudate-putamen and 0.51 in the cortex. Conclusion The level of flow reduction in the caudate-putamen and the cortex after 1 hour is in good correlation with human thresholds of irreversible and reversible ischemic damage, and accordingly, this model might be a model for mechanisms of infarct evolution and therapeutic intervention. J. Magn. Reson. Imaging 2002;15:123,129. © 2002 Wiley-Liss, Inc. [source] Supersensitivity of P2X7 receptors in cerebrocortical cell cultures after in vitro ischemiaJOURNAL OF NEUROCHEMISTRY, Issue 5 2005Kerstin Wirkner Abstract Neuronally enriched primary cerebrocortical cultures were exposed to glucose-free medium saturated with argon (in vitro ischemia) instead of oxygen (normoxia). Ischemia did not alter P2X7 receptor mRNA, although serum deprivation clearly increased it. Accordingly, P2X7 receptor immunoreactivity (IR) of microtubuline-associated protein 2 (MAP2)-IR neurons or of glial fibrillary acidic protein (GFAP)-IR astrocytes was not affected; serum deprivation augmented the P2X7 receptor IR only in the astrocytic, but not the neuronal cell population. However, ischemia markedly increased the ATP- and 2,-3,- O -(4-benzoylbenzoyl)-adenosine 5,-triphosphate (BzATP)-induced release of previously incorporated [3H]GABA. Both Brilliant Blue G and oxidized ATP inhibited the release of [3H]GABA caused by ATP application; the Brilliant Blue G-sensitive, P2X7 receptor-mediated fraction, was much larger after ischemia than after normoxia. Whereas ischemic stimulation failed to alter the amplitude of ATP- and BzATP-induced small inward currents recorded from a subset of non-pyramidal neurons, BzATP caused a more pronounced increase in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) after ischemia than after normoxia. Brilliant Blue G almost abolished the effect of BzATP in normoxic neurons. Since neither the amplitude of mIPSCs nor that of the muscimol-induced inward currents was affected by BzATP, it is assumed that BzATP acts at presynaptic P2X7 receptors. Finally, P2X7 receptors did not enhance the intracellular free Ca2+ concentration either in proximal dendrites or in astrocytes, irrespective of the normoxic or ischemic pre-incubation conditions. Hence, facilitatory P2X7 receptors may be situated at the axon terminals of GABAergic non-pyramidal neurons. When compared with normoxia, ischemia appears to markedly increase P2X7 receptor-mediated GABA release, which may limit the severity of the ischemic damage. At the same time we did not find an accompanying enhancement of P2X7 mRNA or protein expression, suggesting that receptors may become hypersensitive because of an increased efficiency of their transduction pathways. [source] An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2010Naoki Oyama Abstract Hypertension reduces endothelial nitric oxide synthase (eNOS) expression and leads to endothelial dysfunction. However, few studies have demonstrated the influences of hypertension on eNOS function in the cerebral cortex. The present study investigates the influences of hypertension on endothelial function in the cerebral cortex and the protective effects of antihypertensive agents against brain ischemia through the preservation of endothelial function. Five- and ten-week-old male Wistar rats and spontaneously hypertensive rats (SHR) were used for experiments. Five-week-old SHR received olmesartan, hydralazine, or vehicle for 5 weeks in drinking water. eNOS activation in the cerebral cortex was evaluated by analyzing levels of total and Ser1177 -phosphorylated eNOS protein by Western blot. Blood pressure of 10-week-old SHR without treatment was clearly high, and the ratio of phospho-eNOS/total eNOS protein was significantly low. Five-week treatment with olmesartan or hydralazine suppressed the elevation of blood pressure and the reduction of phosphorylated eNOS-Ser1177 in SHR, and olmesartan was more effective in maintaining phosphorylation of eNOS-Ser1177 than hydralazine. To assess the contribution of eNOS to maintaining cerebral blood flow (CBF), we monitored CBF by laser-Doppler flowmetry after L-N5 -(1-iminoethyl)ornithine (L-NIO) infusion. CBF response to L-NIO was preserved in olmesartan-treated SHR but not in hydralazine-treated SHR. Furthermore, infarct volume 48 hr after transient focal brain ischemia in olmesartan-treated SHR was significantly reduced compared with vehicle-treated SHR. These findings indicate that chronic prehypertensive treatment with olmesartan could attenuate brain ischemic injury through the maintenance of endothelial function in the cerebral cortex in SHR. © 2010 Wiley-Liss, Inc. [source] Neurovascular and neuronal protection by E64d after focal cerebral ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2006Tamiji Tsubokawa Abstract Calpains and cathepsins are two families of proteases that play an important role in ischemic cell death. In this study, we investigated the effect of E64d, a ,-calpain and cathepsin B inhibitor, in the prevention of neuronal and endothelial apoptotic cell death after focal cerebral ischemia in rats. Rats underwent 2 hr of transient focal ischemia from middle cerebral artery occlusion (MCAO) and were sacrificed 24 hr later. E64d (5 mg/ kg intraperitoneally) was administered 30 min before MCAO. Assessment included neurological function, infarction volume, brain water content, blood,brain barrier permeability, histology, and immunohistochemistry. The E64d-treated rats had significant brain protection against ischemic damage. We observed a reduction of infarction volume, brain edema, and improved neurological scores in E64d-treated rats compared with the nontreated control. Furthermore, there was a remarkable reduction in both proteases and caspase-3 activation and apoptotic changes in both neurons and endothelial cells in E64d-treated rats. These results suggest that E64d protects the brain against ischemic/reperfusion injury by attenuating neuronal and endothelial apoptosis. © 2006 Wiley-Liss, Inc. [source] Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Petra Henrich-Noack Abstract The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin-induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild ischemia to investigate the effects of preischemic intracerebral thrombin injection on neural damage. By intracerebral injection of endothelin-1 in freely moving animals, we achieved middle cerebral artery occlusion (MCAO), and 7 days postischemia we performed histological quantification of the infarct areas. Thrombin was injected as a preconditioning stimulus intracerebrally 7 days or 2 and 3 days before ischemia. For acute treatment, thrombin was injected 20 min before MCAO. Thrombin induced significant neuroprotection when given 7 days before endothelin-1-induced MCAO but was deleterious when given 2 and 3 days before the insult. The deleterious effect was not seen when thrombin was given acutely before ischemia. Our data demonstrate that preconditioning with thrombin can protect against damage or worsen ischemic damage. Its effect depended on the time interval between thrombin injection and insult. A low dose of thrombin did not induce a major deleterious effect in the acute phase of the infarct development after mild transient ischemia. © 2006 Wiley-Liss, Inc. [source] Resection and reconstruction of retrohepatic vena cava without venous graft during major hepatectomiesJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2007Marcel Autran C. Machado MD Abstract Background Progress in liver surgery has enabled hepatectomy with concomitant venous resection for liver malignancies involving the inferior vena cava (IVC). The authors describe an alternative technique for IVC reconstruction without the need of graft. Methods Parenchymal transection is performed from anterior surface of the liver down to the anterior or left lateral surface of the IVC using combination of two techniques reported elsewhere. IVC is clamped above and below the tumor and the liver in continuity with an invaded segment of IVC is removed en bloc. A transverse anastomosis of IVC is performed starting with running suture on the posterior wall followed by the anterior wall. Results This approach has been successfully employed in eight consecutive patients with IVC involvement. The procedures performed were 5 right hepatectomies, 1 right posterior sectionectomy, 1 right trisectionectomy, and 1 left trisectionectomy. Two patients needed total vascular exclusion (TVE) for 11 and 10 min, respectively. Blood transfusion was necessary in three patients. Pathologic surgical margins were free in all cases. No postoperative mortality was observed. Conclusion This technique of IVC reconstruction precludes the use of graft and minimizes the use of TVE decreasing ischemic damage to the remnant liver. J. Surg. Oncol. 2007;96:73,76. © 2007 Wiley-Liss, Inc. [source] Biliary inorganic phosphate as a tool for assessing cold preservation-reperfusion injury: A study in the isolated perfused rat liver modelLIVER TRANSPLANTATION, Issue 2 2003Luciana L. Almada Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. The bile flow has been suggested as an index of ischemic damage, and severely impaired bile flow seems to be predictive of poor survival in experimental studies. Looking for injury markers, biliary inorganic phosphate has the potential of being a useful endogenous marker of diminished hepatobiliary function because this anion is excreted in the bile by a paracellular pathway and it can detect changes in permeability. The goal of this study was to evaluate the effects of cold preservation-reperfusion of the liver on bile flow and bile inorganic phosphate and their relationship with storage-related graft failure. The isolated and perfused rat liver was used to evaluate the injury for ischemia-reperfusion. The intrahepatic resistance, lactate dehydrogenase release, and potassium and biliary inorganic phosphate concentration were used to estimate viability and function of freshly isolated or cold-preserved livers. The intrahepatic resistance and the bile flow were consistent and significantly decreased throughout the perfusion time in relation to the increment in storage. Inorganic phosphate is more concentrated in bile from preserved livers, showing an alteration in paracellular pathway, confirmed by the biliary excretion of horseradish peroxidase. After preservation, concentration and excretion of the paracellular marker were increased during the first peak. The second peak appears earlier in preserved livers (10 minutes) with a different shape but without changes in concentration. In conclusion, inorganic phosphate in bile shows changes in paracellular permeability as occurs in livers after 48 hours of cold preservation. [source] The water extract of Omija protects H9c2 cardiomyoblast cells from hydrogen peroxide through prevention of mitochondrial dysfunction and activation of caspases pathwayPHYTOTHERAPY RESEARCH, Issue 1 2007Channy Park Abstract The water extract of Omija (Omija) has been used traditionally in the treatment of ischemic damage of the heart and brain tissues. However, little is known about the mechanism by which it rescues myocardial cells from oxidative stress. This study was designed to investigate the protective mechanisms of Omija on H2O2 -induced cytotoxicity in H9c2 cardiomyoblast cells. Treatment with H2O2 resulted in the death of H9c2 cells, characterized by apparent apoptotic features, including fragmentation of the nucleus and an increase in the sub-G0/G1 fraction of the cell cycle. However, Omija markedly suppressed the apoptotic characteristics of H9c2 cells induced by H2O2. In addition, Omija suppressed the features of mitochondrial dysfunction, including changes in the mitochondrial membrane potential and cytosolic release of cytochrome c in H2O2 -treated cells. Treatment with Omija further inhibited the catalytic activation of caspase-9 and caspase-3 and induction of Fas by H2O2. Taken together, these data indicate that the water extract of Omija protects H9c2 cardiomyoblast cells from oxidative stress of H2O2 through inhibition of mitochondrial dysfunction and activation of intrinsic caspase cascades, including caspase-3 and caspase-9. Copyright © 2006 John Wiley & Sons, Ltd. [source] Differential expression of stromal cell,derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implicationsARTHRITIS & RHEUMATISM, Issue 9 2006Paola Cipriani Objective Systemic sclerosis (SSc) is characterized by early endothelial damage evolving to vascular desertification. Stromal cell,derived factor 1 (SDF-1) and its receptor CXCR4 regulate specific steps in new vessel formation. We undertook this study to determine whether an alteration of the SDF-1/CXCR4 axis might be involved in the pathogenetic mechanisms following ischemic damage during SSc. Methods We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by immunohistochemistry, reverse transcription,polymerase chain reaction (RT-PCR), and Western blot analyses. Furthermore, isolated microvascular endothelial cells (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and Western blotting. Results SDF-1 and CXCR4 were up-regulated in the skin of patients with early (edematous) SSc, both in the diffuse and limited cutaneous forms, and progressively decreased, with the lowest expression in the latest phases of both SSc subsets. MVECs from patients with dcSSc expressed significantly higher amounts of both isoforms of SDF-1 in the early stage of disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized in polarized areas, suggesting that they are activated in vivo and that they are under strict genetic control to retain capping function. Conclusion Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc. [source] Fibrosis and Stenosis of the Long Penetrating Cerebral Arteries: the Cause of the White Matter Pathology in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and LeukoencephalopathyBRAIN PATHOLOGY, Issue 4 2004Qing Miao MSc In cerebral autosomal dominant arteriopathy with subcortical infarcts and leuco-encephalopathy (CADASIL) the vascular smooth muscle cells are destroyed and granular osmiophilic material is deposited followed by fibrosis of the arterial wall. To verify whether true stenosis of the fibrotic white matter arteries is a key pathogenic event in CADASIL, we analyzed the thickness of walls (expressed as sclerotic index) and luminal diameters of penetrating arterioles in both grey matter and white matter of four CADASIL patients due to the C475T (R133C) mutation in the Notch3 gene and in 9 age-matched controls. We also reconstructed 9 arterioles from 1000 serial sections in two CADASIL patients. The thickness of the arteriolar walls in both grey matter and white matter was significantly increased in the CADASIL patients compared with controls. Furthermore, in CADASIL patients the arteriolar walls were significantly thicker in the white matter than in the grey matter. The distribution curve of arteriolar internal diameters in CADASIL patients shifted towards smaller sizes. In serial sections, the marked increase in the thickness of the white matter penetrating arterioles or their branches did not occur until the internal diameters had decreased to about 20 to 30 ,m and external diameters to about 100 to 130 ,m. In conclusion, long penetrating arterioles and their branches supplying subcortical structures in CADASIL are stenosed and their walls are thickened. This conforms to the abundance of infarcts and primary ischemic damage in CADASIL patients' white matter. [source] Selective Neuronal Vulnerability Following Mild Focal Brain Ischemia in the MouseBRAIN PATHOLOGY, Issue 4 2003Juri Katchanov The evolution of cellular damage over time and the selective vulnerability of different neuronal subtypes was characterized in the striatum following 30-minute middle cerebral artery occlusion and reperfusion in the mouse. Using autoradiography we found an increase in the density of [3H]PK11195 binding sites,likely reflecting microglial activation,in the lesion border at 3 days and in the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct loss of [3H]flumazenil and [3H]CGP39653 binding sites from 10 days up to 6 weeks reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium spiny projection neurons as seen at three days by Nissl staining, TUNEL and immunocytochemistry using antibodies against microtubule-associated protein (MAP2), NeuN, (,-opioid receptors, substance P, Lenkephalin, neurokinin B, choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch and matrix compartments were involved in ischemic damage. In contrast, the numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in the ischemic striatum were not different from those in the contralateral hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to sequester calcium by calcium-binding proteins and other hitherto unidentified factors may explain this relative resistance of interneurons to acute ischemia. [source] The long-term outcome of tacrolimus in cadaveric kidney transplantation from non-heart beating donorsCLINICAL TRANSPLANTATION, Issue 2 2005Nobuyuki Fukuhara Abstract:, Tacrolimus (Tac), developed in 1990, has been applied as an immunosuppressive agent for liver, heart, and kidney transplantation and is known to have more powerful immunosuppressive effects than cyclosporine (CyA). To evaluate the efficacy of Tac in cadaveric kidney transplants from non-heart beating donors, we present the long-term outcome of patients receiving kidneys with ischemic damage, and compared it with that of CyA. Between July 1990 and December 2000, 55 patients with end-stage renal disease received kidneys from non-heart beating donors (Maastrichy category 3) and were treated with Tac and steroid immunosuppressive therapy. During the same period, we also performed 137 non-heart beating cadaveric renal transplants treated with CyA-based immunosuppressive therapy. The patient survival rate was 98% at 1 yr and 96% at 3,10 yr in the Tac group, and 97% at 1,3 yr, 93% at 5 yr and 85% at 10 yr in the CyA group. The graft survival rate was 91% at 1 yr, 80% at 3 yr, 63% at 5 yr and 34% at 10 yr in the Tac group, and 88% at 1 yr, 75% at 3 yr, 63% at 5 yr and 49% at 10 yr in the CyA group. There was no significant difference in either patient or graft survival rates between the two groups. Acute early rejection in the Tac group was less than that in the CyA group but acute tubular necrosis was the same in both groups. This indicates that Tac is available for cadaveric kidney transplants from non-heart beating donors. In conclusion, Tac is available as an immunosuppressive agent even for kidney transplants from non-heart beating donors. [source] | |||||||||||||