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Ischemic Tissue (ischemic + tissue)
Selected AbstractsArteriolar Remodeling Following Ischemic Injury Extends from Capillary to Large Arteriole in the MicrocirculationMICROCIRCULATION, Issue 5 2008Alexander M. Bailey ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 ,m diameter arterioles. Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia. Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15,35 ,m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6,35 ,m) increased by 24.3%, while chronic hypoxia was absent from all tissues. Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models. [source] Alteration of urothelial-mediated tone in the ischemic bladder: Role of eicosanoids,NEUROUROLOGY AND URODYNAMICS, Issue 3 2004Kazem M. Azadzoi Abstract Aims Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role of urothelium and eicosanoid-release in ischemic bladder smooth muscle instability. Materials and Methods Male New Zealand white rabbits were divided into treated (n,=,12) and age-matched control (n,=,10) groups. The treated group underwent balloon endothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium was removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs). Results A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro,) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro, tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF2-, and thromboxane A2 release from the ischemic suburothelial tissue. Ischemia increased the release of LTB4, LTC4, and LTE4 from both urothelium and suburothelial tissue. Conclusions Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder. Neurourol. Urodynam. 23:258,264, 2004. Published 2004 Wiley-Liss, Inc. [source] Calculation of cerebral perfusion parameters using regional arterial input functions identified by factor analysisJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2006Linda Knutsson MS Abstract Purpose To calculate regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional mean transit time (rMTT) accurately, an arterial input function (AIF) is required. In this study we identified a number of AIFs using factor analysis of dynamic studies (FADS), and performed the cerebral perfusion calculation pixel by pixel using the AIF that was located geometrically closest to a certain voxel. Materials and Methods To verify the robustness of the method, simulated images were generated in which dispersion or delay was added in some arteries and in the corresponding cerebral gray matter (GM), white matter (WM), and ischemic tissue. Thereafter, AIFs were determined using the FADS method and simulations were performed using different signal-to-noise ratios (SNRs). Simulations were also carried out using an AIF from a single pixel that was manually selected. In vivo results were obtained from normal volunteers and patients. Results The FADS method reduced the underestimation of rCBF due to dispersion or delay that often occurs when only one AIF represents the entire brain. Conclusion This study indicates that the use of FADS and the nearest-AIF method is preferable to manual selection of one single AIF. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [source] MRI tissue characterization of experimental cerebral ischemia in ratJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2003Hamid Soltanian-Zadeh PhD Abstract Purpose To extend the ISODATA image segmentation method to characterize tissue damage in stroke, by generating an MRI score for each tissue that corresponds to its histological damage. Materials and Methods After preprocessing and segmentation (using ISODATA clustering), the proposed method scores tissue regions between 1 and 100. Score 1 is assigned to normal brain matter (white or gray matter), and score 100 to cerebrospinal fluid (CSF). Lesion zones are assigned a score based on their relative levels of similarities to normal brain matter and CSF. To evaluate the method, 15 rats were imaged by a 7T MRI system at one of three time points (acute, subacute, chronic) after MCA occlusion. Then they were killed and their brains were sliced and prepared for histological studies. MRI of two or three slices of each rat brain (using two DWI (b = 400, b = 800), one PDWI, one T2WI, and one T1WI) was performed, and an MRI score between 1 and 100 was determined for each region. Segmented regions were mapped onto the histology images and scored on a scale of 1,10 by an experienced pathologist. The MRI scores were validated by comparison with histology scores. To this end, correlation coefficients between the two scores (MRI and histology) were determined. Results Experimental results showed excellent correlations between MRI and histology scores at different time points. Depending on the reference tissue (gray matter or white matter) used in the standardization, the correlation coefficients ranged from 0.73 (P < 0.0001) to 0.78 (P < 0.0001) using the entire dataset, including acute, subacute, and chronic time points. This suggests that the proposed multiparametric approach accurately identified and characterized ischemic tissue in a rat model of cerebral ischemia at different stages of stroke evolution. Conclusion The proposed approach scores tissue regions and characterizes them using unsupervised clustering and multiparametric image analysis techniques. The method can be used for a variety of applications in the field of computer-aided diagnosis and treatment, including evaluation of response to treatment. For example, volume changes for different zones of the lesion over time (e.g., tissue recovery) can be evaluated. J. Magn. Reson. Imaging 2003;17:398,409. © 2003 Wiley-Liss, Inc. [source] Modulation of ERK and JNK activity by transient forebrain ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Deborah A. Shackelford Abstract The mitogen-activated protein (MAP) kinase families of ERK and JNK participate in numerous intracellular signaling pathways and are abundantly expressed in the CNS. Activation of ERK and JNK during reperfusion of ischemic tissue is implicated in promoting cell death, insofar as inhibition of either pathway reduces neuronal cell death. However, ERK or JNK activation provides protection in other neuronal injury models. In this study, we monitored the concurrent modulation of ERK and JNK activity in the hippocampus, neocortex, and striatum during ischemia and immediately upon reperfusion in a rat model of transient global ischemia. All three regions incur a similar reduction in blood flow during occlusion but show different extents and temporal patterns of injury following reperfusion. ERK and JNK were active in the normal rat forebrain, and phosphorylation was reduced by ischemia. Upon reperfusion, ERK was rapidly activated in the hippocampus, neocortex, and striatum, whereas JNK phosphorylation increased in the hippocampus and striatum but not in the neocortex. The response of JNK vs. ERK more closely reflects the susceptibility of these regions. JNK1 was the predominant phosphorylated isoform. A minor pool of phosphorylated JNK3 increased above the control level after reperfusion in hippocampal but not in neocortical particulate fractions. In addition, a novel 32,35-kDa c-Jun kinase activity was detected in the hippocampus, neocortex, and striatum. The results show that ERK and JNK activities are rapidly, but not identically, modulated by ischemia and reperfusion and indicate that the MAP kinase pathways contribute to regulating the response to acute CNS injury. © 2006 Wiley-Liss, Inc. [source] Mapping ischemic risk region and necrosis in the isolated heart using EPR imagingMAGNETIC RESONANCE IN MEDICINE, Issue 6 2003Murugesan Velayutham Abstract Reperfusion of ischemic tissue is a common event in the treatment of heart attack and stroke. To study disease pathogenesis, methods are required to measure tissue perfusion and area at risk, as well as localized regions of injury. While histology can provide this information, its destructive nature precludes assessment of time course. Thus, there is a critical need for a noninvasive technique to obtain this information. To map myocardial redox state as a possible index of cellular ischemia and viability, electron paramagnetic resonance (EPR) imaging experiments were performed on isolated rat hearts before and after the onset of regional ischemia using nitroxide spin labels. With coronary artery occlusion, the EPR images clearly showed the risk region as a void of lower intensity that reversed upon reperfusion. The extent of risk region in the heart was similar in EPR imaging and histological measurements. The unique information obtained regarding the time course of changes in redox metabolism of the risk region and normal myocardium can provide important insights regarding the mechanisms of myocardial injury during and following ischemia. Magn Reson Med 49:1181,1187, 2003. © 2003 Wiley-Liss, Inc. [source] Randomized, controlled trial of insulin for acute poststroke hyperglycemiaANNALS OF NEUROLOGY, Issue 5 2010Michael McCormick MD Objective Poststroke hyperglycemia is common and is associated with increased risk of death and dependence, but appropriate management remains uncertain. Glucose potassium insulin (GKI) infusion did not benefit patients with moderate poststroke hyperglycemia in a recent trial. Using magnetic resonance imaging (MRI), previous studies identified a relationship between recruitment of ischemic tissue to the final infarct and hyperglycemia, possibly mediated by brain lactic acidosis. Methods We undertook a randomized, placebo-controlled trial of GKI infusion in patients with blood glucose >126mg/dl (7mmol/l) within 24 hours of ischemic stroke. The primary endpoint was infarct growth on MRI between baseline and day 7. Brain lactate concentrations were measured with magnetic resonance spectroscopy. Results Forty patients were randomized, 15 to saline and 25 to GKI infusions of different durations. Capillary blood glucose concentrations were lowered significantly from 6 to 12 hours after GKI initiation. There was no significant difference on any measure of infarct growth between the GKI and saline groups. In a secondary analysis, GKI was associated with significantly greater infarct growth in patients with complete intracranial vessel occlusion compared with controls (p = 0.011 for group,vessel status interaction). Brain lactate levels increased in control subjects, but were significantly lower with GKI infusion. Predominantly asymptomatic hypoglycemia occurred in 76% of GKI-treated subjects. Interpretation GKI infusion within 24 hours of stroke lowered blood glucose and attenuated an increase in brain lactate, but did not affect cerebral infarct growth. Exploratory analysis found that GKI infusion was associated with greater infarct growth in patients with persistent arterial occlusion, and with a high incidence of asymptomatic hypoglycemia. ANN NEUROL 2010;67:570,578 [source] Delta2 -Specific Opioid Receptor Agonist and Hibernating Woodchuck Plasma Fraction Provide Ischemic NeuroprotectionACADEMIC EMERGENCY MEDICINE, Issue 3 2008Meera Govindaswami PhD Abstract Objectives:, The authors present evidence that the , opioid receptor agonist Deltorphin-Dvariant (Delt-Dvar) and hibernating woodchuck plasma (HWP), but not summer-active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue. Methods:, Cerebral ischemia was produced in wild-type and NO synthase,deficient (NOS,/,) mice by transient, 1-hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt-Dvar at 2.0 and 4.0 mg/kg, or 200 ,L of HWP or SAWP. NOS,/, mice were treated with either saline or Delt-Dvar at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with ,- or ,-specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon-,. Nitrate in the medium was measured as an indicator of NO production. Results:, Infusion of Delt-Dvar or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS,/, mice, endothelial NOS+/+ is required to provide Delt-Dvar,induced neuroprotection. Delt-Dvar and HWP dose-dependently decreased NO release in cell culture, while SAWP and other ,- and ,-specific opioids did not. Conclusions:, Delt-Dvar and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release. [source] Enhancement of Viability of Fat Grafts in Nude Mice by Endothelial Progenitor CellsDERMATOLOGIC SURGERY, Issue 12 2006CHENGGANG YI MD BACKGROUND A recent discovery showed that endothelial progenitor cells (EPCs) could augment collateral vessel growth to ischemic tissues. OBJECTIVE The objective was to demonstrate the effects of EPCs on the vasculogenesis and survival of free transplanted fat tissues in nude mice. METHODS EPCs from human donors were cultured in vitro for 7 days. Human fat tissues were injected subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with CM-DiI were mixed with the transplanted fat tissues and injected into the mice. EBM-2 medium was used as control group. The animals were euthanized 15 weeks after the procedure. Graft volume were measured, and histologic evaluation was performed. The central part of fat tissues was histologically evaluated 15 weeks after the fat injection. RESULTS The survival volume of the experimental group was significantly greater than that of the control group (p< .05). Less cyst formation and fibrosis was obtained in the experimental group. Histologic evaluation of the central part of fat tissues 15 weeks after the fat injection showed that capillary densities increased markedly in the experimental group mice. CONCLUSION The results indicate that EPCs have the ability to enhance the survival and the quality of the transplanted fat tissues. [source] Human hematopoietic stem/progenitor-enriched CD34+ cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarctionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005E. Paczkowska Abstract:, The hematopoietic and non-hematopoietic stem/progenitor cells harvested directly from the bone marrow (BM) or G-CSF mobilized peripheral blood were demonstrated to play an important role in regeneration of damaged organs (1, 2). Here, we asked if the stroke- or acute heart infarct-related stress triggers mobilization of stem/progenitor-enriched CD34+cells from the BM into the peripheral blood, which subsequently could contribute to regeneration of damaged tissues. To address this question the peripheral blood samples were harvested from patients with ischemic stroke during the first 24 h of manifestation of symptoms and on the second and sixth day afterwards or during the first 24 h of acute cardiac pain as well as on the second and sixth day of infarct. We measured in these patients (i) percentage of circulating hematopoietic stem/progenitor-enriched CD34+ cells in peripheral blood by employing fluorescence activated cell sorter (FACS) and (ii) number of hematopoietic progenitor cells for the granulocyte-monocytic colony-forming unit (CFU-GM) and erythoid burst-forming unit (BFU-E) lineages circulating in peripheral blood. We concluded that stress related to ischemic stroke or acute myocardial infarction triggers the mobilization of hematopoietic stem/progenitor-enriched CD34+ cells from the BM into peripheral blood. These circulating stem/progenitor-enriched CD34+ cells may contribute to the regeneration of ischemic tissues, however, this possibility requires further studies. [source] Impairment of endothelial cell differentiation from bone marrow,derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 6 2007P. Cipriani Objective Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair. Methods MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit,fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed. Results MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell,derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls. Conclusion Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc. [source] | ||||||||||