Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage.
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PMID:Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study. 1178 46

Reactive oxygen species (ROS) generated by mitochondrial respiration and other processes are often viewed as hazardous substances. Indeed, oxidative stress, defined as an imbalance between oxidant production and antioxidant protection, has been linked to several neurological disorders, including cerebral ischemia-reperfusion and Parkinson's disease. Consequently, cells and organisms have evolved specialized antioxidant defenses to balance ROS production and prevent oxidative damage. Research in our laboratory has shown that neuronal levels of ascorbate, a low molecular weight antioxidant, are ten-fold higher than those in much less metabolically active glial cells. Ascorbate levels are also selectively elevated in the CNS of anoxia-tolerant reptiles compared to mammals; moreover, plasma and CSF ascorbate concentrations increase markedly in cold-adapted turtles and in hibernating squirrels. Levels of the related antioxidant, glutathione, vary much less between neurons and glia or among species. An added dimension to the role of the antioxidant network comes from recent evidence that ROS can act as neuromodulators. One example is modulation of dopamine release by endogenous hydrogen peroxide, which we describe here for several mammalian species. Together, these data indicate adaptations that prevent oxidative stress and suggest a particularly important role for ascorbate. Moreover, they show that the antioxidant network must be balanced precisely to provide functional levels of ROS, as well as neuroprotection.
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PMID:Brain antioxidant regulation in mammals and anoxia-tolerant reptiles: balanced for neuroprotection and neuromodulation. 1245 80

The relation between cerebral ischemia and local release of angiogenic factors was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular, cisternal, and lumbar) were analyzed in 15 patients surgically treated for ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V). Data were related to brain Po2 (Pbro2) and cerebral energy metabolites (extracellular lactate, pyruvate, glutamate, and glycerin concentrations) as well as clinical and radiologic reference data. Delayed impairment of cerebral perfusion secondary to progressive microcirculatory alterations was associated with reduced local Pbro2 and energy metabolism (increased lactate-pyruvate ratio, glutamate and glycerine levels). Elevated serum/plasma and CSF concentrations of VEGF, sFlt-1, and sTie-2 matched the scale of ischemic tissue hypoxia. Excessive VEGF/sFlt-1 and sTie-2 levels were related to Pbro2 values consistently less than 5 mm Hg, glutamate concentrations greater than 300 micromol/L, lactate-pyruvate ratio greater than 300, cerebral infarction, and reduced outcome (P < 0.01). Delayed microcirculatory impairment was mirrored by distinct elevation of cisternal and arterial VEGF and sFlt-1 concentrations, suggesting local induction of angiogenesis. Arterial levels of VEGF, sFlt-1, and sTie-2 reflect both extent and time course of compensatory, yet clinically inefficient, angiogenesis in the absence of general hypoxia.
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PMID:Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man. 1250 95

The Call-Fleming syndrome is characterized by sudden onset of thunderclap-like headache and focal neurological deficits. The pathophysiological correlate is a reversible segmental cerebral vasoconstriction frequently associated with focal cerebral ischaemia. The syndrome has been described in a variety of clinical conditions, and recently an association between the syndrome and exposure to vasoactive drugs was observed. Effective treatment options are not known. A 63-year-old female developed sudden 'worst ever' headache. Initial neurological examination, laboratory blood tests, CSF examination and brain magnetic resonance imaging (MRI) were normal. Previous medical history was unremarkable and she did not take vasoactive drugs. Eleven days after the onset of headache she developed visual field impairment and a right-sided hemiparesis. Brain MRI revealed bilateral posterior and left parietal ischaemic strokes. Cerebral catheter angiography showed segmental arterial vasoconstriction. A vasodilative therapy with calcium channel inhibitors was started and serial transcranial Doppler ultrasonography demonstrated resolution of cerebral arterial vasoconstriction. The present case illustrates that calcium channel inhibitors may be an effective therapy for segmental cerebral arterial vasoconstriction. However, more clinical data are needed to prove this observation.
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PMID:Reversible segmental cerebral vasoconstriction (Call-Fleming syndrome): are calcium channel inhibitors a potential treatment option? 1266 81

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours (r = 0.85, P<0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume (r = -0.40 and r = -0.35, respectively, P<0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days (P<0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.
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PMID:L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study. 1290 42

Free fatty acids (FFAs) are elevated in the brain following both ischemic and traumatic injury. Phospholipase activation, with the subsequent release of FFAs from membrane phospholipids, is the likely mechanism. In addition to phospholipases A1, B, C, and D, there are at least 19 groups of PLA2, including multiple cytosolic, calcium independent, and secretory isoforms. Phospholipase activity can be regulated by calcium, by phosphorylation, and by agonists binding to G-protein-coupled receptors. These enzymes normally function in the physiological remodeling of cellular membranes, whereby FFAs are removed by phospholipase activity and then reacylated with a different FFA. However, reductions in the cell's ability to maintain normal metabolic function and the resultant fall in ATP levels can cause the failure of reacylation of membrane phospholipids. Alterations to membrane phospholipids would be expected to compromise many cellular functions, including the ability to accumulate excitotoxic amino acids. This review presents evidence for a central role of phospholipases and their products in the etiology of damage following injury to the brain. Phospholipase expression and activity is increased in animal models of cerebral ischemia and trauma. FFA release from the in vivo rat brain is reduced following the application of selective phospholipase inhibitors, and this inhibition also decreases the severity of cortical damage following forebrain ischemia, focal (middle cerebral artery occlusion) ischemia, and cerebral trauma. Mice with knockouts of PLA2 have decreased infarct volumes. Human data demonstrate a correlation between the elevation of CSF FFAs and worsened outcome following stroke, traumatic brain injury, and subarachnoid hemorrhage. The released FFAs, especially arachidonic and docosahexaenoic acids, together with the production of lysophospholipids, can initiate a chain of events which may be responsible for the development of neuronal damage. Inhibitors of both cyclooxygenase and lipoxygenase pathways have been shown to reduce cerebral deficits following ischemia and trauma. These results suggest therapeutic strategies to reduce morbidity following cerebral injury using selective inhibitors of phospholipases, cyclooxygenases, and lipoxygenases, underlining the need for further investigation of their role in the development of cerebral damage.
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PMID:The role of phospholipases, cyclooxygenases, and lipoxygenases in cerebral ischemic/traumatic injuries. 1451 63

Cytokines play a key role in mutual influence of the immunological, endocrine and CNS systems. It has been proven that proinflammatory ILs may intensify the cascade of biochemical changes in ischemic brain damage. Vasospasm, which may accompany SAH and often coexists with symptoms of DINDs, is the cause of ischemic changes in the brain. It is thought that immunological mechanisms may be one of the causes of degenerative-productive changes in vessel walls, in delayed vasospasm following SAH, which lead to substantial vasospasm and in consequence too cerebral ischemia. In the randomly selected group of patients, who underwent surgical treatment after aneurysmal SAH, we determined the concentration of IL-1 beta and IL-6 in CSF in the periods between Days 0 to 3; 4 to 7; and 8 to 15 after the occurrence of SAH. The presence and dynamics of development of vasospasm were assessed on the basis of increasing DINDs as well as CT and cerebral angiography. We examined the concentrations of ILs in CSF using radioimmunological methods, applying commercially available tests for their assessment. We found that in the period between 8 and 15 days after SAH, in increasing delayed vasospasm and DINDs, here is a statistically significant increase concentration of IL-1 beta in CSF (105.4 +/- 46.9 pg x ml-1; p<0.005), and no significant changes in patients without vasospasm and neurological deficits. On the other hand, we noted a statistically significant increase concentration of IL-6 in CSF (4802 +/- 1170 ng x ml-1; p<0.05) only in the acute phase after SAH (Days 0-3) in patients in poor clinical condition, in whom delayed vasospasm and cerebral ischemia developed later. This increase of ILs level in CSF is probably related to the intensity of the SAH, and secondarily aggravates the vasospasm and ischemic changes in the brain.
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PMID:Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. 1515 98

Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted (DW) MRI has been established as a highly sensitive technique for assessing acute cerebral ischemia, its role in spinal cord infarction remains to be determined. The purpose of this study is to present the signal characteristics of acute spinal cord ischemia using DWMRI within the first two days and after one week. MRI including DW imaging (DWI) was performed in three patients with acute spinal cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated after one week in two patients. Two initial scans included EPI DW sequences in transverse and sagittal orientation. The remaining examinations were performed with an optimised high-spatial resolution DWI sequence in the transverse plane. The diagnosis of spinal cord ischemia was established by imaging, clinical history and CSF analysis. T2 signal abnormality and restricted diffusion was demonstrated in all initial examinations. Transverse DW sequences had the highest sensitivity. The spinal infarctions were mainly located in the centre of the spinal cord and the grey matter. Contrast enhancement was absent. After one week, the restricted diffusion had normalised (pseudo normalisation) whereas the T2 signal changes had become more prominent. Restricted diffusion in the course of spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a diffusion abnormality can be found after few hours, it does not last for longer than one week. At this time, the establishment of the diagnosis has to rely mainly on T2-weighted images with additional post contrast T1-weighted images being useful.
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PMID:Diffusion-weighted MRI of spinal cord infarction--high resolution imaging and time course of diffusion abnormality. 1525 83

The inflammation accompanies and exacerbates cerebral ischaemia. The infiltrated leucocytes are thought to contribute to tissue injury in stroke patients. GRO-alpha (CXCL1) is a potent neutrophil chemoattractant which may play an important role in pathophysiology of stroke. 23 ischaemic stroke patients and 15 controls have been studied. CSF and blood sampling together with cranial CT were performed within first 24 hours of stroke. CXCL1 levels were determined by ELISA, and volume of stroke-related brain CT hypodense areas was calculated. Stroke patients displayed significantly higher CSF CXCL1 level than controls (65.6+/-22.3 vs 43.8+/-2.3 pg/ml; p<0.01). Serum CXCL1 levels in stroke patients did not differ from controls. CSF CXCL1 level correlated positively with volume of brain CT hypodense areas (p<0.001). The results suggest that CXCL1 may be involved in inflammatory reaction during an early phase of ischaemic stroke.
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PMID:CXCL1 (GRO-alpha) chemokine in acute ischaemic stroke patients. 1601 11

We investigated the molecular mechanisms of the anti-apoptotic properties of granulocyte-colony stimulating factor (G-CSF) on neurons and whether G-CSF affects glial cell survival following focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to a transient 90 min middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Rats were treated with either a single dose of G-CSF (50 microg/kg, s.c.) at the onset of reperfusion or G-CSF (50 microg/kg body weight, s.c.) was administered starting at the onset of reperfusion and followed by the administration of the same dose per day for an additional 2 days. Brains were harvested either 24 h, 72 h or 2 weeks after reperfusion for assays of infarct volume, immunohistological studies and Western blot analysis for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Pim-1, bcl-2, Bax, cytochrome c, cellular inhibitor of apoptosis protein 2 (cIAP2), and cleaved caspase-3 levels. G-CSF significantly reduced infarct volume and ameliorated the early neurological outcome. G-CSF treatment significantly up-regulated pSTAT3, Pim-1, bcl-2 expression, and down-regulated cytochrome c release to the cytosol, Bax translocation to the mitochondria, and cleaved caspase-3 levels in neurons. The activation of the STAT3 pathway was accompanied by increased cIAP2 expression in glial cells. After MCAO, G-CSF treatment increased both neuronal and glial survival by effecting different anti-apoptotic pathways which reflects the multifactorial actions of this drug. These changes were associated with remarkable improvement in tissue preservation and behavioral outcome.
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PMID:Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat. 1708 35


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