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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the generation of nitric oxide (NO) is an essential step in the trigger phase of ischemic preconditioning, short-term inhalation of NO before ischemia should ameliorate ischemia/reperfusion (I/R) injury of the lung. We tested this hypothesis in high oxygen (>99%) ventilated rats in order to additionally evaluate compatibility of NO and exposure to hyperoxia. Male adult Sprague-Dawley rats inhaled NO (15 ppm, 10 min) before the left lung hilum was clamped for 1 h, and the reperfusion phase was observed for 4 h (NO group). Animals in the I/R group underwent the same treatment, but without NO inhalation. A third group without I/R served as time-matched controls. Animals in the I/R group showed severe I/R injury in terms of arterial pO2 (apO2), which was reduced to 22% of surgical controls (SCs) at time point 30 min reperfusion, and increased endothelial permeability (Evans blue procedure). The pretreatment with NO attenuated these effects. The pO2 after 4 h reperfusion was still 3.0-fold higher in the NO group compared to I/R. In contrast, the I/R- and hyperoxia-induced invasion of leukocytes, as determined by measuring myeloperoxidase (MPO) activity, was not affected by NO. These data were correlated with the activity of major cellular signaling pathways by measuring the phosphorylation at activating and inhibitory sites of extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, protein kinase B (AKT), and glycogen synthase kinase 3beta (GSK-3beta), and by determination of cGMP in plasma and lung tissue. Inhalation of NO partly prevented the loss of activation by I/R and hyperoxic ventilation of ERK, JNK, and AKT, and it reduced the I/R-induced activation of GSK-3beta. The level of cGMP in plasma and lung tissue was increased in the NO group after 4 h reperfusion. In conclusion, application of inhaled NO in the preconditioning mode prevented I/R injury in the rat lung without interfering effects of hyperoxic ventilation. The effects of NO on cellular signaling pathways resemble mechanisms of ischemic preconditioning, but further studies have to evaluate the physiological relevance of these results.
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PMID:Preconditioning by inhaled nitric oxide prevents hyperoxic and ischemia/reperfusion injury in rat lungs. 1845 45

We evaluated the potential neuroprotective effects of combination treatment with normobaric hyperoxia (NBO) and edaravone, a potent scavenger of hydroxyl radicals, on acute brain injuries after stroke. Mice subjected to 2-h filamental middle cerebral artery occlusion were treated with NBO (95% O2, during the ischemia) alone, with edaravone (1.5 mg/kg, intravenously after the ischemia) alone, with both of these treatments (combination), or with vehicle. The histological and neurological score were assessed at 22-h after reperfusion. Infarct volume was significantly reduced in the combination group [36.3+/-6.7 mm3 (n=10) vs. vehicle: 65.5+/-5.9 mm3 (n=14) P<0.05], but not in the two monotherapy-groups [NBO: 50.5+/-5.8 mm3 (n=14) and edaravone: 56.7+/-5.8 mm3 (n=10)]. The combination therapy reduced TUNEL-positive cells in the ischemic boundary zone both in cortex [6.0+/-1.4 x 10(2)/mm2 (n=5) vs. vehicle: 18.9+/-2.4 x 10(2)/mm2 (n=5), P<0.01] and subcortex [11.6+/-1.5 x 10(2)/mm2 (n=5) vs. vehicle: 22.5+/-2.1 x 10(2)/mm2 (n=5), P<0.01]. NBO and combination groups exhibited significantly reduced neurological deficit scores at 22-h after reperfusion (vs. vehicle, P<0.05). Combination therapy with NBO plus edaravone prevented the neuronal damage after focal cerebral ischemia and reperfusion in mice, compared with monotherapy of NBO or edaravone.
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PMID:Combination effects of normobaric hyperoxia and edaravone on focal cerebral ischemia-induced neuronal damage in mice. 1857 23

The generation of reactive oxygen species (ROS) in the vasculature plays a major role in the genesis of endothelial cell (EC) activation and barrier function. Of the several potential sources of ROS in the vasculature, the endothelial NADPH oxidase family of proteins is a major contributor of ROS associated with lung inflammation, ischemia/reperfusion injury, sepsis, hyperoxia, and ventilator-associated lung injury. The NADPH oxidase in lung ECs has most of the components found in phagocytic oxidase, and recent studies show the expression of several homologues of Nox proteins in vascular cells. Activation of NADPH oxidase of nonphagocytic vascular cells is complex and involves assembly of the cytosolic (p47(phox), p67(phox), and Rac1) and membrane-associated components (Noxes and p22(phox)). Signaling pathways leading to NADPH oxidase activation are not completely defined; however, they do appear to involve the cytoskeleton and posttranslation modification of the components regulated by protein kinases, protein phosphatases, and phospholipases. Furthermore, several key components regulating NADPH oxidase recruitment, assembly, and activation are enriched in lipid microdomains to form a functional signaling platform. Future studies on temporal and spatial localization of Nox isoforms will provide new insights into the role of NADPH oxidase-derived ROS in the pathobiology of lung diseases.
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PMID:Regulation of NADPH oxidase in vascular endothelium: the role of phospholipases, protein kinases, and cytoskeletal proteins. 1882 98

Anesthesia may be an important factor in maximizing the success of microsurgery by controlling the hemodynamics and the regional blood flow. The intraanesthetic basic goal is to maintain an optimal blood flow for the vascularized free flap by: increasing the circulatory blood flow, maintaining a normal body temperature to avoid peripheral vasoconstriction, reducing vasoconstriction resulted from pain, anxiety, hyperventilation, or some drugs, treating hypotension caused by extensive sympathetic block and low cardiac output. A hyperdynamic circulation can be obtained by hypervolemic or normovolemic hemodilution and by decrease of systemic vascular resistance. The importance of proper volume replacement has been widely accepted, but the optimal strategy is still open to debate. General anesthesia combined with various types of regional anesthesia is largely preferred for microvascular surgery. Maintenance of homeostasis through avoidance of hyperoxia, hypocapnia, and hypovolemia (all factors that can decrease cardiac output and induce local vasoconstriction) is a well-established perioperative goal. As the ischemia-reperfusion injury could occur, inhalatory anesthetics as sevoflurane (that attenuate the consequences of this process) seem to be the anesthetics of choice.
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PMID:Anesthesia for free vascularized tissue transfer. 1894 83

Oxygen-induced retinopathy (OIR) in the mouse, like the analogous human disease retinopathy of prematurity, is an ischemic retinopathy dependent on oxygen-induced vascular obliteration. We tested the hypothesis that chemically overriding the oxygen-induced downregulation of hypoxia-inducible factor (HIF) activity would prevent vascular obliteration and subsequent pathologic neovascularization in the OIR model. Because the degradation of HIF-1alpha is regulated by prolyl hydroxylases, we examined the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in the OIR model. Our results determine that stabilizing HIF activity in the early phase of OIR prevents the oxygen-induced central vessel loss and subsequent vascular tortuosity and tufting that is characteristic of OIR. Overall, these findings imply that simulating hypoxia chemically by stabilizing HIF activity during the causative ischemia phase (hyperoxia) of retinopathy of prematurity may be of therapeutic value in preventing progression to the proliferative stage of the disease.
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PMID:Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. 1905 8

Normally, brain tissue copes with negative oxygen balance by increasing cerebral blood flow (CBF). We examined the effects of increasing oxygen demand, by inducing spreading depression (SD) under various oxygen balance states, on brain O2 balance. The Tissue Vitality Monitoring System was used, which enables real time simultaneous in vivo monitoring of CBF, mitochondrial NADH and tissue HbO2 from the same region of the cerebral cortex. SD was induced during normoxia, hypoxia, hyperoxia, ischemia, and in normal and ischemic brain after systemic epinephrine administration. Under normoxia, hyperoxia and ischemia & epinephrine, the compensation of energy demand induced by SD, was carried out by increasing CBF. The higher oxygen delivery under hyperoxia and epinephrine did not change the pattern of recovery from SD as compared to normoxia, whereas in the ischemic and hypoxic brain, the recovery from SD was prolonged, indicating a lake in oxygen delivery. Epinephrine infusion in the ischemic rat, decreased oxyhemoglobin utilization during SD, indicating that tissue oxygen balance improves even under higher oxygen demand induced by SD.
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PMID:Brain oxygen balance under various experimental pathophysiologycal conditions. 1922 85

Recent studies suggest that intermittent and prolonged normobaric hyperoxia results in ischemic tolerance to reduce ischemia brain injury. In this research attempts were made to see the changes in antioxidant enzyme activities following prolonged and intermittent normobaric hyperoxia preconditioning. Rats were divided into four experimental groups, each of 21 animals. The first two were exposed to 95% inspired normobaric hyperoxia for 4 h/day for 6 consecutive days (intermittent normobaric hyperoxia) or for 24 h continuous (prolonged normobaric hyperoxia). The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion-operated, sham-operated (without middle cerebral artery occlusion), and intact (without any surgery) subgroups. After 24 h, middle cerebral artery occlusion-operated subgroups were subjected to 60 min of right middle cerebral artery occlusion. After 24 h reperfusion, neurologic deficit score, infarct volume were measured in middle cerebral artery occlusion-operated subgroups. Antioxidant enzyme activities were assessed in sham-operated and intact subgroups. Preconditioning with prolonged and intermittent normobaric hyperoxia decreased neurologic deficit score and infarct volume, and increased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the intermittent and prolonged normobaric hyperoxia seems to partly exert their effects via increase antioxidant enzymes activities.
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PMID:In vivo normobaric hyperoxia preconditioning induces different degrees of antioxidant enzymes activities in rat brain tissue. 1930 5

Normobaric hyperoxia (NBO) and cilostazol (6-[4-(1-cyclohexy-1H-tetrazol-5-yl)butoxyl]-3,4-dihydro-2-(1H)-quinolinone) (a selective inhibitor of phosphodiesterase 3) have each been reported to exert neuroprotective effects against acute brain injury after cerebral ischemia in rodents. Here, we evaluated the potential neuroprotective effects of combination treatment with NBO and cilostazol against acute and subacute brain injuries after simulated stroke. Mice subjected to 2-h filamental middle cerebral artery (MCA) occlusion were treated with NBO (95% O(2), during the ischemia) alone, with cilostazol (3 mg/kg i.p. after the ischemia) alone, with both of these treatments (combination), or with vehicle. The histological and neurobehavioral outcomes were assessed at acute (1 day) or subacute (7 days) stages after reperfusion. We measured regional cerebral blood flow (rCBF) during and after ischemia by laser-Doppler flowmetry and recovery (versus vehicle) in the combination therapy group just after reperfusion. Mean acute and subacute lesion volumes were significantly reduced in the combination group but not in the two monotherapy groups. The combination therapy increased endothelial nitric-oxide synthase (eNOS) activity in the lesion area after ischemia versus vehicle. Combination therapy with NBO plus cilostazol protected mice subjected to focal cerebral ischemia by improvement of rCBF after reperfusion, in part in association with eNOS activity.
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PMID:Combination treatment with normobaric hyperoxia and cilostazol protects mice against focal cerebral ischemia-induced neuronal damage better than each treatment alone. 1933 63

There are several forms of acute pediatric brain injury, including neonatal asphyxia, pediatric cardiac arrest with global ischemia, and head trauma, that result in devastating, lifelong neurologic impairment. The only clinical intervention that appears neuroprotective is hypothermia initiated soon after the initial injury. Evidence indicates that oxidative stress, mitochondrial dysfunction, and impaired cerebral energy metabolism contribute to the brain cell death that is responsible for much of the poor neurologic outcome from these events. Recent results obtained from both in vitro and animal models of neuronal death in the immature brain point toward several molecular mechanisms that are either induced or promoted by oxidative modification of macromolecules, including consumption of cytosolic and mitochondrial NAD(+) by poly-ADP ribose polymerase, opening of the mitochondrial inner membrane permeability transition pore, and inactivation of key, rate-limiting metabolic enzymes, e.g., the pyruvate dehydrogenase complex. In addition, the relative abundance of pro-apoptotic proteins in immature brains and neurons, and particularly within their mitochondria, predisposes these cells to the intrinsic, mitochondrial pathway of apoptosis, mediated by Bax- or Bak-triggered release of proteins into the cytosol through the mitochondrial outer membrane. Based on these pathways of cell dysfunction and death, several approaches toward neuroprotection are being investigated that show promise toward clinical translation. These strategies include minimizing oxidative stress by avoiding unnecessary hyperoxia, promoting aerobic energy metabolism by repletion of NAD(+) and by providing alternative oxidative fuels, e.g., ketone bodies, directly interfering with apoptotic pathways at the mitochondrial level, and pharmacologic induction of antioxidant and anti-inflammatory gene expression.
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PMID:Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury. 1942 8

Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.
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PMID:Protective effects of topiramate against hyperoxic brain injury in the developing brain. 1963 24


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