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)

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.
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PMID:Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion. 1082 28

Paraplegia remains to be one of the most dangerous complications following thoracoabdominal aortic surgery with an incidence of 0.5 to 40%. Therefore, intraoperative monitoring of spinal cord function is very important when choosing the appropriate surgical technique. Early detection of spinal cord injury continues to be a crucial problem, moreover, the currently applied electrophysiological methods appear to be inaccurate. The aim of the study was to detect prospective spinal cord injury intraoperatively by monitoring the biochemical parameters of the cerebrospinal fluid (CSF). The authors studied the reversible aerobic/anaerobic metabolic changes by monitoring CSF lactate levels, moreover S-100 protein and neuron-specific enolase (NSE) concentrations--specific for neuroglia and neuronal injury, respectively. One of the important methods to prevent paraplegia is the intraoperative CSF drainage, which may improve spinal cord perfusion. Between 1996-1998 51 patients underwent reconstructive thoracic or thoracoabdominal aortic aneurysm operation. The continuously drained CSF was collected in 10 ml fractions during the preparation, whereas during aortic cross-clamping and de-clamping 10 minute fractions were used. All CSF samples were immediately analysed intraoperatively for pH, pCO2, HCO3, potassium and lactate levels, S-100 protein and NSE were analysed by immunoluminescence. CSF lactate levels increased slightly during aortic clamping and a moderate, but non-significant increase was found in the hyperemic phase (reperfusion) in patients without spinal cord ischemia. Spinal cord injury was detected in 7 cases. These patients exhibited a significant CSF-lactate increase (control vs aortic cross-clamping: 1.9 vs 5.3 mmol/l), moreover CSF-lactate remained elevated throughout the whole operation. Paraplegia did not occur, Tarlov 2 paraparesis developed in four cases and three patients displayed cerebral damage. Intraoperative CSF--especially CSF-lactate--monitoring may help the operating team to detect early anaerobic changes of the metabolism the spinal cord.
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PMID:[New method for the intraoperative biochemical monitoring of cerebrospinal fluid in surgery of thoracoabdominal aortic aneurysms]. 1093 38

For a model of neurological disease and ischemia, we extended recent work to culture adult postmortem rat brain neurons. Frontal cortex sections were removed from adult rats immediately following sacrifice and at different postmortem intervals and with the brain at either 22 degrees C or 4 degrees C. Brain could be stored four times longer at 4 degrees C between sacrifice and neuronal disaggregation to achieve the same 20% recovery of live cells from those plated compared to 22 degrees C. Each milligram of rat frontal cortex was estimated by the optical disector method to contain 160,000 neurons. When cells were isolated as rapidly as possible, 9% of the neurons originally present in the brain were viable. Various postmortem intervals from 2 to 24 hr resulted in a reduction from 6% to 3% of the cells originally present. After 5 days in culture, viable neurons were 23-42% of those isolated. Neuron-like cells that survived represented 40-75% of the viable cells, or 0.5-2.75% of those originally estimated to be present in the brain. Electrophysiology experiments show that cells isolated 0 and 24 hr postmortem had neuronal electrical properties, including an average resting membrane potential of -48 mV, voltage-sensitive currents, and action potentials. Neuron-like cells were immunoreactive for neuron-specific enolase, neurofilament 200, glutamate, MAP2, and tau after 2 weeks in culture. These experiments show that neuron-like cells can be reliably cultured from adult rat cortex up to 6 hr postmortem when stored at 22 degrees C and up to 24 hr postmortem when stored at 4 degrees C. These findings should encourage donation of human postmortem brain neurons for studies on ischemia, adult pharmacology, and neurological disease.
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PMID:Temperature and time interval for culture of postmortem neurons from adult rat cortex. 1134 Jun 37

Spinal cord damage during and after thoracoabdominal aortic cross-clamping continues to be a major problem. Somatosensory and motor evoked potentials have been used to monitor spinal cord function but their value for predicting paraplegia has been controversial. The aim of this study was to measure biochemical markers in the cerebrospinal fluid (CSF) and correlate changes with spinal cord ischemia. Since neural tissue utilizes only glucose as substrate for its metabolism and energy supply, we measured changes of metabolites of anaerobe glycolysis. In a canine model in which general anesthesia was used, the thoracoabdominal aorta was cross-clamped proximally and distally for 60 min. Hemodynamic parameters, blood gases, and glucose level were monitored continuously. Blood and CSF sampling were performed at baseline, at 15, 30, and 55 min during cross-clamping, and at 5 and 15 min after aortic declamping. Levels of lactate (1.7 +/- 0.1 to 3.2 +/- 0.3 mmol/L), pCO2 (43 +/- 2 to 35 +/- 1.6 mmHg), and neuron-specific enolase (NSE) (5.17 +/- 0.5 to 13.0 +/- 3.5 mg/L) in CSF showed significant changes (p < 0.05) during clamping and reperfusion. Changes in CSF lactate and NSE levels correlate with the duration of spinal cord ischemia. These markers of ischemic metabolism appear suitable to monitor the degree of spinal cord ischemia during thoracoabdominal cross-clamping and may be useful to predict the efficacy of preventive methods.
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PMID:Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs. 1208 29

Postpartum hemorrhage (PPH) is a frequent complication of pregnancy in India. Sheehan's description of postpartum hypopituitarism promoted the belief that PPH leads to necrosis of the enlarged pituitary gland of pregnancy and hypopituitarism. However, slow clinical progression suggests factors other than ischemia in its pathogenesis. Tissue necrosis could release sequestered antigens, triggering autoimmunity of the pituitary and delayed hypopituitarism in Sheehan's syndrome. Twenty-six consecutive patients with postpartum hypopituitarism were studied, 19 with Sheehan's syndrome based on a history of PPH and hormone profile suggesting pituitary failure [mean (SD) age 32.7 +/- 6.4 yr, duration of illness 5.5 +/- 3.1 yr], and seven patients with no history of PPH, categorized as "Other." Pituitary imaging and basal T(4), TSH, cortisol, LH, FSH, 17beta-estradiol, and autoantibodies against pituitary (PitAb) and thyroid (TMA) were evaluated. Controls included 28 healthy females without prior conception (22 +/- 5 yr) and 28 with prior conception (26 +/- 5 yr). Twelve of 19 (63.1%) patients with Sheehan's syndrome and one of seven in the Other group had PitAb against the 49-kDa autoantigen; neuron-specific enolase. Four of 28 (14.2%) controls without prior conception and 5 of 28 (17.8%) controls with prior conception had PitAb positivity (P < 0.001 and <0.01 vs. Sheehan's syndrome, respectively). There was no significant difference in the mean serum hormone values and TMA positivity between patients with Sheehan's syndrome and the Other group as well as patients with or without PitAb positivity. Pituitary autoimmunity may play a role in the cause of hypopituitarism following PPH.
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PMID:Pituitary autoimmunity in patients with Sheehan's syndrome. 1221 61

The objective of this research was to determine the dynamics of change of neuron-specific enolase concentration in patients with acute ischemic brain disease in cerebrospinal fluid and plasma. The study included 103 patients, their mean age 58-66 years. The control group consisted of 16 patients, of matching age and sex, with radicular lesions of discal origin, subjected to diagnostic radiculography. Concentration of neuron-specific enolase was measured by a flouroimmunometric method. The results showed that the concentration of neuron-specific enolase in cerebrospinal fluid and plasma of patients with brain ischemic disease within first seven days significantly increased compared to the control. The highest increase of concentration was established in brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack. Maximal concentration was established on the 3rd-4th day upon the brain infarction. Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an indicator of pathophysiological processes in the acute phase of brain ischemia and is significant in early diagnostics and therapy of the disease.
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PMID:Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute ischemic brain disease. 1458 48

Various regions of the brain have been successfully transduced by recombinant adeno-associated virus (rAAV) vectors with no detected toxicity. When using the cytomegalovirus immediate early (CMV) promoter, a gradual decline in the number of transduced cells has been described. In contrast, the use of cellular promoters such as the neuron-specific enolase promoter or hybrid promoters such as the chicken beta-actin/CMV promoter resulted in sustained transgene expression. The cellular tropism of rAAV-mediated gene transfer in the central nervous system (CNS) varies depending on the serotype used. Serotype 2 vectors preferentially transduce neurons whereas rAAV5 and rAAV1 transduce both neurons and glial cells. Recombinant AAV4-mediated gene transfer was inefficient in neurons and glial cells of the striatum (the only structure tested so far) but efficient in ependymal cells. No inflammatory response has been described following rAAV2 administration to the brain. In contrast, antibodies to AAV2 capsid and transgene product were elicited but no reduction of transgene expression was observed and readministration of vector without loss of efficiency was possible from 3 months after the first injection. Based on the success of pioneer work performed with marker genes, various strategies for therapeutic gene delivery were designed. These include enzyme replacement in lysosomal storage diseases, Canavan disease and Parkinson's disease; delivery of neuroprotective factors in Parkinson's disease, Huntington disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemia and spinal cord injury; as well as modulation of neurotransmission in epilepsy and Parkinson's disease. Several of these strategies have demonstrated promising results in relevant animal models. However, their implementation in the clinics will probably require a tight regulation and a specific targeting of therapeutic gene expression which still demands further developments of the vectors.
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PMID:Recombinant AAV-mediated gene delivery to the central nervous system. 1497 64

Neurological complications contribute significantly to morbidity and mortality of patients after orthotopic liver transplantation (OLT). One possible cause of postoperative neurological complications is cerebral ischemia during the surgical procedure. In this study, we investigated the relationship between intraoperative changes in regional cerebral oxygen saturation (rSo(2)) and postoperative values of neuron-specific enolase (NSE) and S-100, which are specific variables that indicate cerebral disturbances due to hypoxia/ischemia. The rSo(2) was monitored continuously by near-infrared spectroscopy in 16 patients undergoing OLT. In addition, NSE and S-100 were determined in arterial blood before surgery and 24 h after reperfusion of the donor liver. Interestingly, clamping of the recipient's liver led to a significant decline in rSo(2) in eight patients, whereas the others tolerated clamping without major changes in rSo(2). The decrease in rSo(2) after clamping correlated significantly with postoperative increases in NSE (r(2) = 0.57) and S-100 (r(2) = 0.52). However, there were no significant differences between patients with and without rSo(2) decline concerning hemodynamic variables. There were no significant correlations between DeltarSo(2) and cardiac output (r(2) = 0.20), NSE and cardiac output (r(2) = 0.37), or S-100 and cardiac output (r(2) = 0.24). Monitoring of rSo(2) may be a useful noninvasive tool to estimate disturbances in rSo(2) during OLT.
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PMID:Regional cerebral oxygen saturation is a sensitive marker of cerebral hypoperfusion during orthotopic liver transplantation. 1527 2

Several studies have shown that high corticosteroid hormone levels increase neuronal vulnerability. Here we evaluate the consequences of in vivo acute or repeated restraint stress on cellular viability in rat hippocampal slices suffering an in vitro model of ischemia. Cellular injury was quantified by measuring lactate dehydrogenase (LDH) and neuron-specific enolase released into the medium. Acute stress did not affect cellular death when oxygen and glucose deprivation (OGD) was applied both immediately or 24h after restraint. The exposure to OGD, followed by reoxygenation, resulted in increased LDH in the medium. Repeated stress potentiated the effect of OGD both, on LDH and neuron-specific enolase released to the medium. There was no effect of repeated stress on the release of S100B, an astrocytic protein. Additionally, no effect of repeated stress was observed on glutamate uptake by the tissue. These results suggest that repeated stress increases the vulnerability of hippocampal cells to an in vitro model of ischemia, potentiating cellular damage, and that the cells damaged by the exposure to repeated stress+OGD are mostly neurons. The uptake of glutamate was not observed to participate in the mechanisms responsible for rendering the neurons more susceptible to ischemic damage after repeated stress.
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PMID:Acute and repeated restraint stress influences cellular damage in rat hippocampal slices exposed to oxygen and glucose deprivation. 1583 99

The aim of this clinical and experimental study was to determine whether systemic neuron-specific enolase (NSE) is a useful early marker of traumatic brain injury (TBI) and whether NSE is affected by ischemia/reperfusion damage of abdominal organs. Our study included patients with and without TBI (verified by computerized tomography) admitted within 6 h after trauma and male Sprague-Dawley rats with ischemia and reperfusion of the abdominal organs liver, gut, or kidney. Thirty-eight study patients included 13 with isolated TBI and 18 patients with multiple trauma and TBI. Seven patients had multiple trauma but no TBI. Fifteen rats were anaesthetized and subjected to isolated ischemia of the liver, gut, or kidney (n = 5 each) for 1 h, followed by reperfusion for 3 h. In patients, NSE increased over 2-fold versus the upper normal limit (10 microg/L) within 6 h after trauma, regardless of whether TBI had occurred or not. In rats, NSE increased over 3-fold versus laboratory controls during ischemia of the liver and kidney (both P < 0.0005), but not of the gut. NSE increased over 2-fold after onset of reperfusion of the liver and kidney (both P < 0.05), but not of the gut and increased over 3-fold after 3 h of reperfusion of the liver, gut (both P < 0.005), and kidney (P < 0.0005). Our data show that systemic NSE increases to similar degrees with and without TBI. Therefore, NSE is not a useful early marker of TBI in multiple trauma.
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PMID:Nonspecific increase of systemic neuron-specific enolase after trauma: clinical and experimental findings. 1604 81


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