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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radicals are implicated as causative agents in various forms of tissue destruction. Considerable circumstantial evidence suggests that oxygen-based free radicals generated as blood flow returns to formerly ischemic brain areas are mainly responsible for the neurodegeneration that follows periods of cerebral ischemia. In general, oxygen-based free radicals are highly reactive and exist for only a brief period of time. This makes the direct measurement of many of these free radicals rather difficult. Much of the current knowledge of free radicals in cerebral ischemia is based on observations of chemical changes brought about by the free radicals rather than on direct observations of the free radicals themselves. Low temperature electron paramagnetic resonance spectroscopy is one method that allows the direct study of free radicals. Compared to samples from sham-operated controls, samples of hippocampus taken from gerbils exposed to 15 min of forebrain ischemia followed by 15 min of reperfusion, frozen in liquid nitrogen less than 20 sec after sacrifice, and scanned by low temperature (100 K) electron paramagnetic resonance, show a significant increase in oxygen-based free radicals and a decrease in carbon-based ubiquinone-like free radicals. The ischemia-induced increase in oxygen-based free radicals is prevented by the intraperitoneal injection of the antioxidant drug U-78517F at the start of reperfusion and by hypothermia. However, neither intervention alters the ischemia-induced reduction in the ubiquinone-like free radicals. This suggests that the neuroprotective actions of hypothermia and U-78517F include a direct reduction in the oxygen-based free radical burden of the post-ischemic tissue.
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PMID:Neuroprotective effects of hypothermia and U-78517F in cerebral ischemia are due to reducing oxygen-based free radicals: an electron paramagnetic resonance study with gerbils. 884 89

Recently, attention has been focused on the degradation of cytoskeletal proteins in animal models of cerebral ischemia, as the collapse of cytoskeletal proteins may be closely related to cytoskeletal disintegration and ultimate neuronal cell death. Among these proteins, microtubule-associated protein 2 (MAP2) has been shown to be highly vulnerable to ischemic injuries. To determine the degree of anesthetic effect on the collapse of cytoskeletal proteins, we compared the effect of three inhalation anesthetics; isoflurane, halothane, and nitrous oxide (N2O), on MAP2 degradation during 20 min of forebrain ischemia in the rat. Under equipotent anesthesia, forebrain ischemia was induced by the occlusion of the bilateral common carotid artery (CCA) combined with a lowering of mean arterial pressure (mAP) to 50 mmHg. After 20 min of ischemia, three regions of the brain, the frontoparietal cortex, brainstem, and hippocampus, were removed and separately homogenized. Subsequently, MAP2 of each region was measured using an enzyme-linked immunosorbent assay (ELISA). In the frontoparietal cortex and hippocampus, MAP2 was significantly protected from degradation when isoflurane was used combined with nitrogen (N2). However, the protective effects of isoflurane were drastically reduced when N2O was given instead of N2. These results suggest that the use of N2O should be discontinued when severe cerebral ischemia is accidentally incurred during anesthetic management.
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PMID:Nitrous oxide attenuates the protective effect of isoflurane on microtubule-associated protein2 degradation during forebrain ischemia in the rat. 932 46

This protocol describes a model of cerebral ischemia based on organotypic hippocampal slice cultures and quantitative assessment of cell death by use of propidium iodide and image analysis. The cultures were made from rat hippocampal slices that were obtained at postnatal day 4-7 and allowed to develop for >14 days in vitro. For induction of 'in vitro ischemia', the cultures were washed in glucose free buffer and the culture chamber flooded with a nitrogen/carbon dioxide mixture until the oxygen concentration was <1.0%. The cultures were exposed to this atmosphere for 30-35 min, washed in serum-free medium, and returned to ordinary growth medium. After 24 h, dead cells were quantified by use of propidium iodide. The cell death resulting from the oxygen/glucose deprivation was largely confined to the CA1 region and was blocked by NMDA-receptor antagonists but not by antagonists to AMPA-receptors or metabotropic glutamate receptors. The type of cell death was judged to be necrotic, based on ultrastructural observations. The oxygen/glucose deprived cultures exhibited increased phosphorylation of the MAP kinase cascade. This activation of the MAP kinase cascade was blocked by NMDA-receptor antagonists. The in vitro model described in the present report is simple to use and reproduces many features of in vivo ischemia, including the preferential vulnerability of CA1 cells. The model should be suited to analyses of the mechanisms underlying the regionally selective cell death in the hippocampus and ischemic cell death in general.
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PMID:A simple in vitro model of ischemia based on hippocampal slice cultures and propidium iodide fluorescence. 1044 12

The role of the adenosine A3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A3 receptors and, based on the available evidence, discusses the possibility of adenosine A3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.
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PMID:Stimulation of adenosine A3 receptors in cerebral ischemia. Neuronal death, recovery, or both? 1066 16

Determination of extent of infarction in animal models of cerebral ischemia is most commonly achieved by either classical histology (thionin staining) and light microscopy or staining with 2,3, 5-triphenyltetrazolium chloride (TTC). These techniques have limitations and we now describe a novel technique and its validation for assessment of the neuroprotective activity of AM-36, a novel arylalkypiperazine compound with combined antioxidant and sodium channel blocking activity. AM-36 (1.8 mg/kg i.p.) or vehicle, was administered 30 min, 24 and 48 h after endothelin-1-induced middle cerebral artery occlusion in conscious rats. Rats were killed at 72 h, brains removed and frozen in liquid nitrogen prior to coronal sectioning. Using a simple apparatus relying on basic principles of light propagation and a computerised image analysis system, ischemic damage in unstained slide-mounted sections was clearly visualised and measured. AM-36 significantly reduced the area of infarct in both cortex and striatum. The method was verified by thionin staining, and light microscopy. Linear regression analysis showed a highly significant correlation between methods at 72 h for infarct area in the cortex and striatum. Highly significant correlations between methods were found at 3 and 24 h after ischemia. Our method quickly and clearly delineates areas of damage in a manner superior to conventional staining methods.
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PMID:A novel, rapid, computerized method for quantitation of neuronal damage in a rat model of stroke. 1100 Apr 11

Free radicals are highly reactive molecules implicated in the pathology of traumatic brain injury and cerebral ischemia, through a mechanism known as oxidative stress. After brain injury, reactive oxygen and reactive nitrogen species may be generated through several different cellular pathways, including calcium activation of phospholipases, nitric oxide synthase, xanthine oxidase, the Fenton and Haber-Weiss reactions, by inflammatory cells. If cellular defense systems are weakened, increased production of free radicals will lead to oxidation of lipids, proteins, and nucleic acids, which may alter cellular function in a critical way. The study of each of these pathways may be complex and laborious since free radicals are extremely short-lived. Recently, genetic manipulation of wild-type animals has yielded species that over- or under-express genes such as, copper-zinc superoxide dismutase, manganese superoxide dismutase, nitric oxide synthase, and the Bcl-2 protein. The introduction of the species has improved the understanding of oxidative stress. We conclude here that substantial experimental data links oxidative stress with other pathogenic mechanisms such as excitotoxicity, calcium overload, mitochondrial cytochrome c release, caspase activation, and apoptosis in central nervous system (CNS) trauma and ischemia, and that utilization of genetically manipulated animals offers a unique possibility to elucidate the role of free radicals in CNS injury in a molecular fashion.
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PMID:Free radical pathways in CNS injury. 1106 54

Diabetic hyperglycemia increases brain damage after cerebral ischemia in animals and humans, although the underlying mechanisms remain unclear. Gender-linked differences in ischemic tolerance have been described but have not been studied in the context of diabetes. In the current study, we used a model of unilateral common carotid artery ligation, combined with systemic hypoxia, to study the effects of diabetes and gender on hypoxic-ischemic (HI) brain damage in the genetic model of Type II diabetes, the db/db, mouse. Male and female, control and db/db, mice were subjected to right common carotid artery ligation followed by varying periods of hypoxia (8% oxygen/92% nitrogen) to assess mortality, infarct volume, and tissue damage by light microscopic techniques. End-ischemic regional cerebral blood flow (CBF) was determined using [14C] iodoantipyrine autoradiography. Glycolytic and high energy phosphate compounds were measured in blood and brain by enzymatic and fluorometric techniques. Gender and diabetes had significant effects on mortality from HI and extent of brain damage in the survivors. Female mice were more resistant than their male counterparts, such that the severity (mortality and infarction size) in the male diabetics > female diabetics - male controls > female controls. Endischemic CBF and depletion of cerebral high energy reserves were comparable among all groups. Surprisingly, female diabetic mice were more hyperglycemic and demonstrated a greater prolonged lactacidosis than the males; however, they were more resistant to damage. The results suggest a unique pathophysiology of hypoxia-ischemia in the female diabetic brain.
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PMID:Experimental stroke in the female diabetic, db/db, mouse. 1114 68

A timed profile of glutathione oxidation and reactive nitrogen species during reperfusion after cerebral ischemia in rat was obtained. Dialysate was collected every 25 min from a microdialysis probe inserted into the cerebral cortex before and after cerebral ischemia. NO2-, NO3-, and reduced and oxidized glutathione (GSH, GSSG) were detected by high-performance liquid chromatography. GSH and GSSG increased and reached a peak: 3408 +/- 1710% (mean +/- SE) at 25 min of reperfusion (P < 0.0001) and 329 +/- 104% at 50 min of reperfusion (P = 0.06), respectively. Oxidation ratio decreased from 0.82 +/- 0.04 to 0.42 +/- 0.07 (P < 0.0001) at 25 min of reperfusion. NO3- levels significantly decreased (68.3 +/- 9.1%) (P < 0.01) during ischemia and remained lower than the control value during reperfusion. NO2- levels did not significantly change. These data suggest that GSH releases during early phase of reperfusion and that its rapid oxidation contributes to prevent an increase in reactive nitrogen species.
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PMID:Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia. 1219 54

The Platelet Activating Factor (PAF) is believed to be the major function in human after cerebral vascular spasm and cerebral ischemia. PAF has been found to participate in cerebral vascular spasm and cerebral ischemia by the basic and clinical study. The symptom of cerebral vascular spasm and cerebral ischemia has appeared with SAH. It has not been reported that the rule and change of PAF with SAH. In the present work, the concentration of PAF in human cerebral spinal fluid (CSF) with SAH were determined by high performance layer thin chromatography. The TLC plate was coated with high performance silica gel G using V(chloroform):V(methanol):V(water) = 65:35:6 as developing solvent. The PAF was determined by TLC scanning method and detected at 630 nm. The method was applied to determine the concentration of PAF in 16 CSF samples with SAH. The samples were collected in 1-3 d, 7-10 d and 14-21 d. CSF samples were deproteinized with methanol and chloroform. After centrifugation, the chloroform layer separated was dried at room temperature with nitrogen and stored under 20 degrees C in the refrigerator. The linear range of the method was 0.5-2.5 micrograms/L with regression coefficient of 0.9990. The lower limit of detection were 50 ng/L. The recovery of the method was 98.6%. The method enables a simple, rapid and reproducible quantification of PAF with SAH.
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PMID:[High performance thin layer chromatographic (HPTLC) determination of PAF in cerebrospinal fluid of patients with subarachnoid hemorrhage(SAH)]. 1255 2

Glutamine has multiple physiological and pathophysiological roles in the brain. Because of their position at the interface between blood and brain, the cerebral capillaries and the choroid plexuses that form the blood-brain barriers (BBB) and blood-cerebrospinal fluid (CSF) barriers, have the potential to influence brain glutamine concentrations. Despite this, there has been a paucity of data on the mechanisms and polarity of glutamine transport at these barrier tissues. In situ brain perfusion in the rat, indicates that blood to brain L-[14C]glutamine transport at the blood-brain barrier is primarily mediated by a pH-dependent, Na(+)-dependent, System N transporter, but that blood to choroid plexus transport is primarily via a pH-independent System N transporter and a Na(+)-independent carrier that is not System L. Transport studies in isolated rat choroid plexuses and primary cultures of choroid plexus epithelial cells indicate that epithelial L-[14C]glutamine transport is polarized (apical uptake>basolateral) and that uptake at the apical membrane is mediated by pH dependent System N transporters (identified as SN1 and SN2 by polymerase chain reaction) and the Na(+)-independent System L. Blood-brain barrier System N transport is markedly effected by cerebral ischemia and may be a good marker of endothelial cell dysfunction. The multiple glutamine transporters at the blood-brain and blood-CSF barriers may have role in meeting the metabolic needs of the brain and the barrier tissues themselves. However, it is likely that the main role of these transporters is removing glutamine, and thus nitrogen, from the brain.
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PMID:Glutamine transport at the blood-brain and blood-cerebrospinal fluid barriers. 1274 70


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