Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enolase in cerebrospinal fluid is a sensitive marker for many types of neurological injuries including head injury and ischemia. We assessed neuron-specific enolase (NSE) as a quantitative and specific biochemical marker of neuronal damage in an experimental model of kainate neurotoxicity. Rat hippocampal cultures were treated with various concentrations of kainate. NSE release into the culture medium was compared with neuronal death estimated either by direct cell counting or by lactate dehydrogenase (LDH) release, largely used to quantify neuronal injury. A dose-response relationship was observed between kainate concentration and the amount of NSE released (r = -0.69; p < 0.05) as well as a significant correlation between NSE release and neuronal death (r = 0.64; p < 0.05). Likewise, a significant correlation was found between LDH and NSE release (r = 0.85; p < 0.05). The specificity of NSE as an indicator of neuronal death was demonstrated using immunocyto-chemistry labeling and measurement of NSE release by pure astrocyte cultures. We concluded that NSE is a reliable, quantitative, and specific marker of neuronal injury.
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PMID:Neuron-specific enolase as a marker of in vitro neuronal damage. Part I: Assessment of neuron-specific enolase as a quantitative and specific marker of neuronal damage. 849 Mar 8

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.
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PMID:CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. 850 98

The objective of this review is to provide an overview of the use of biochemical markers for the detection of Central Nervous System (CNS) complications after cardiac surgery and extracorporeal circulation (ECC). A computerized literature search in MEDLINE from 1966 onward was the basis for the references. The literature covering the following biochemical markers is reviewed: adenylkinase, creatine phosphokinase isoenzyme BB (CK-BB), lactate, neuron-specific enolase (NSE), S-100 protein, myelin basic protein, lactate dehydrogenase, aspartate aminotransferase, glutathione, vasointestinal neuropeptide, and 7B2-specific neuropeptide. For clinical purposes, it is necessary to have a biochemical marker that can be measured in blood. Lactate, although a primary marker of anaerobic metabolism, and CK-BB values, calculated from the arterio-internal jugular venous difference, appear to correlate with periods of ischemia during ECC. S-100 protein levels have been shown to correlate with duration of ECC, and when combined with NSE values, could be used to identify patients with CNS dysfunction after cardiac surgery. The use of NSE may be limited by its presence in erythrocytes and platelets because the high levels that can result from hemolysis can render it less specific. Although recently introduced, S-100 protein may have the potential to be a valuable marker for CNS dysfunction after ECC.
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PMID:Markers of cerebral ischemia after cardiac surgery. 863 77

Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in patients with acute ischemic stroke as compared with the controls. The altered CSF NSE levels were well correlated with the infarct size in CT scan. The CSF NSE levels were higher in 6-patients who were diagnosed as multi-infarct dementia (MID) after 6-month follow-up than in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE for dementia related to ischemic stroke is worth further studying.
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PMID:[Neuro-specific enolase in acute ischemic stroke and related dementia patients]. 920 70

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF and other physiological parameters were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 29%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 27%, 37%, and 52%, respectively. Nicardipine also reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.
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PMID:Attenuation of brain injury and reduction of neuron-specific enolase by nicardipine in systemic circulation following focal ischemia and reperfusion in a rat model. 934 82

The prognostic value of ubiquitin levels in cerebrospinal fluid (CSF) was studied in human global brain ischemia (anoxic-ischemic encephalopathy). Twenty four samples were collected from 13 patients who were resuscitated from cardio-pulmonary arrest and survived for at least 1 day. The outcome was classified according to the Glasgow Outcome Scale (GOS1-5). The ubiquitin levels (normal: 14.3 +/- 1.1 ng/ml, mean +/- S.E.M.) in neurologically symptomatic patients (GOS1-4) were 151 +/- 32.5 ng/ml on day 1-2 and elevated to 1,960 +/- 849 ng/ml on day 3-4. The Spearman's rank correlation of ubiquitin levels on day 3-4 and the GOS was -0.855, showing a better correlation than CSF neuron-specific enolase levels (r = -0.846). Ubiquitin is a heat shock protein associated with the degradation of abnormal cellular proteins. Thus, the elevation of CSF ubiquitin levels represents both its overproduction by a cytoprotective response to brain ischemia and its leakage from the damaged tissue. The present study suggests that the measurement of CSF ubiquitin level is useful for the early prognostic assessment of global brain ischemia.
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PMID:[An increase in cerebrospinal fluid ubiquitin in human global brain ischemia--a prognostic marker for anoxic-ischemic encephalopathy]. 950 64

Neuron-specific enolase (NSE) is a sensitive marker of brain damage in stroke, global ischemia, and coma. Serum NSE is also correlated with the duration and outcome of status epilepticus (SE). CSF-NSE levels have not been previously reported in SE. We report the CSF concentrations of NSE in 11 patients with cryptogenic/remote symptomatic SE. CSF obtained within 24 hours of SE showed increased concentrations of NSE in 9 of 11 patients. The mean CSF-NSE for the group was elevated compared with the levels for normal control subjects (30.8 +/- 18.33 versus 10.76 +/- 3.08 ng/mL; p = 0.002). Further, CSF-NSE levels were elevated compared with simultaneous serum levels in the same group of patients (p = 0.01). In addition, the CSF/serum albumin ratio (QAlb), a measure of the integrity of the blood-brain barrier, was increased in SE patients compared with control individuals (33.4 versus 4.79 x 10(-3); p = 0.0001). An increase of QAlb correlated with CSF-NSE (rs = 0.66, p = 0.04) and serum NSE levels (rs = 0.83, p = 0.004). CSF-NSE is a promising in vivo marker for brain injury after SE.
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PMID:Status epilepticus increases CSF levels of neuron-specific enolase and alters the blood-brain barrier. 959 92

Heme oxygenase-1 (HO-1, HSP32) is an early gene that is responsive to an array of pathological conditions including, but not limited to, hypoxia and cerebral ischemia. HO-1 cleaves the heme molecule and produces carbon monoxide (CO) and biliverdin (an antioxidant) and is essential for iron homeostasis. The purpose of this study was to investigate, using transgenic (Tg) mice, whether overexpression of HO-1 in the brain augments or attenuates cellular injury caused by ischemic stroke. Homozygous HO-1 Tg mice that overexpress HO-1 under the control of the neuron-specific enolase promoter (characterized previously) were used. Under halothane anesthesia and normothermic conditions, wild-type nontransgenic (nTg; n = 22) and HO-1 Tg (n = 24) mice were subjected to middle cerebral artery occlusion (MCAo). Six hours after induction of ischemia, Tg and nTg mice developed infarcts that were 39 +/- 6 and 63 +/- 9 mm3, respectively (p < 0.01). No significant difference between the two strains was observed in the values of brain edema (11.3 +/- 4% in Tg vs. 14.6 +/- 5% in nTg; p < 0.1). At 24 h after MCAo, Tg mice exhibited significant neuroprotection as determined by the stroke volumes (41 +/- 2 mm3 in Tg vs. 74 +/- 5 mm3 in nTg; p < 0.01) and values of ischemic cerebral edema (21 +/- 6% in Tg vs. 35 +/- 11% in nTg; p < 0.01). Data suggest that neuroprotection in Tg mice was, at least in part, related to the following findings: (a) constitutively up-regulated cyclic GMP and bcl-2 levels in neurons; (b) inhibition of nuclear localization of p53 protein; and (c) antioxidant action of HO-1, as detected by postischemic neuronal expression of ferritin, and decreases in iron staining and tissue lipid peroxidation. We suggest that pharmacological stimulation of HO-1 activity may constitute a novel therapeutic approach in the amelioration of ischemic injury during the acute period of stroke.
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PMID:Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. 1003 92

In contrast to its known anti-apoptotic activity in sympathetic neurons, immortal neuronal cell lines, and primary cultured immature neurons of the central nervous system (CNS), the role of Bcl-2 in CNS neurons in the adult brain is poorly understood. In the present study, we examined effects of overexpression of Bcl-2 on selective neuronal death of the hippocampal CA1 neurons and the dentate granule cells induced by hypoxic ischemia in adult transgenic mice overexpressing human Bcl-2 under the control of neuron-specific enolase (NSE-hbcl-2). At the light microscopic level, numbers of TUNEL-positive cells with pyknotic nuclei were observed in the CA1 subfield of NSE-hbcl-2 transgenic mice, as well as that of wild-type mice, after hypoxic ischemic insult, although the onset of neuronal death was apparently delayed in NSE-hbcl-2 transgenic mice. The electron microscopic studies showed that morphological changes of the degenerating CA1 neurons from both groups were clearly distinct from ordinary apoptosis. In contrast, a significant amount of degenerating dentate granule cells from wild-type but not from transgenic mice had typical apoptotic nuclei by the treatment. The activation of caspase-3 was detected in the dentate granule cells but not that of the CA1 neurons. These results indicate that the overexpression of Bcl-2 effectively suppressed dentate granule cell apoptosis but only delayed cell death of the CA1 neurons induced by hypoxic ischemia, suggesting the occurrence of a non-apoptotic, caspase-3-independent mechanism for neuronal death in the CA1 subfield.
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PMID:Differential effects of Bcl-2 overexpression on hippocampal CA1 neurons and dentate granule cells following hypoxic ischemia in adult mice. 1039 30

The temporal pattern of protein synthesis inhibition was examined in grafted neocortical neurons using [(3)H]valine in vivo autoradiography. Neuronal uptake levels of systemically administered (3)H-labeled amino acids which cross the blood-brain barrier (BBB) via endothelial cell neutral carriers have long been a hallmark in studies of experimental ischemic pathology; there is likely a strong correlation between persistent protein synthesis inhibition and the progression of cell damage. Because the grafting procedure involves the loss of blood flow and the subsequent reperfusion of the donor tissue there are, mechanistically, important similarities to reversible ischemia models. The effects of ischemic injury on grafted CNS neurons are not fully understood. Quantitative analysis of grain distribution in individual graft or control (adjacent host cortex) neurons indicated an initial breakdown of the amino acid barrier system, subsequent recovery, and progressive reduction of amino acid uptake by 1 year. Up to 3 weeks after surgery grafts were flooded with the [(3)H]valine tracer but individual neurons contained relatively few silver grains. After this time, the tracer was normally distributed within graft neurons but at significantly lower levels than in controls. Grain density gradually decreased over time such that 12-month grafted neurons had approximately half that compared to control and only 58% of that in 2-month grafts; the 12-month levels were comparable to those observed at early (10 days) postoperative times. Autoradiography of immunostained sections for MAP-2, SMI 311 (neurofilament marker), and neuron-specific enolase showed reduced expression of these proteins in neurons coupled with weak amino acid tracer uptake. The results further suggest that grafted neurons bear intriguing similarities to neurons placed at ischemic risk, particularly "penumbral" neurons, which are affected by reduced blood flow and are metabolically weakened. The loss of BBB properties in early grafts may also extend to the endothelial cell amino acid carrier system, and the delayed revascularization process could affect neuronal uptake mechanisms.
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PMID:Protein synthesis inhibition in neocortical grafts evaluated by systemic amino acid uptake autoradiography. 1073 33


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