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 permeability-surface area product (PS) of [1-14C]arachidonate at the blood-retina and blood-brain barrier was determined by short carotid perfusion in young Wistar rats 1 or 6 h after recovery period following complete cerebral ischemia induced by temporary cardiac arrest. For the retina and structures of visual system, hypothalamus and olfactory bulb there was no significant difference over sham-operated rats among mean PSs. For cortex, hippocampus and striatum, significant increases were found at both time intervals of recovery after cardiac arrest. The ischemia-reperfusion model was characterized by a significant increase in tissue conjugated diene in the hippocampus and microsomal lysophosphatidylcholine acyltransferase activity in the cortex. Consistent with these findings, we also show ultrastructural evidence mainly represented by partial opening of interendothelial junctions and mild signs of tissue edema in surrounding neuropil, suggesting barrier leakiness predominantly in the cortex, hippocampus and striatum but almost absent in the retina microvessels. Our results indicate that ischemia-reperfusion does affect influex through blood-brain barrier into regional structures of rat central nervous system of arachidonate, a metabolic substrate and lipid mediator rapidly incorporated into microcapillary and brain lipids. The data also suggested that: (i) reactive oxyradicals were moderately generated during the early phase of ischemic-reperfusion process in the rat; (ii) after reperfusion, in vitro susceptibility of different brain regions to iron-induced peroxidation was highest in the hippocampus and lowest in the cortex and striatum; (iii) membrane phospholipid repair mechanisms were activated at the same time.
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PMID:Arachidonate transport through the blood-retina and blood-brain barrier of the rat after reperfusion of varying duration following complete cerebral ischemia. 976 83

The temperature dependence of transmitter release associated with axonal conduction, evoked by ligand-gated mechanism and by reversed operation of plasma membrane transporter was studied in superfused slice preparation. When the temperature was reduced from 37-17 degrees C the release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) in response to field stimulation was significantly enhanced in slice preparations of the hippocampus and main olfactory bulbs. The release of [3H]dopamine evoked by a ligand-gated mechanism (nicotine receptor stimulation) was potentiated at low temperature (12 degrees C). In contrast, when transmitter release was evoked by ouabain, a drug inhibiting Na+/K+-activated ATPase and thereby increasing [Na+]i the release of [3H]GABA was enhanced. This release was very sensitive to cooling (Q10=3.5 between 37 degrees C and 27 degrees C), indicating that the release was induced by a reversed operation of the transporter. The excessive release of [3H]NA from the hippocampal slice in response to oxygen and glucose deprivation (simulation of ischemia) was also inhibited in a temperature-dependent manner. Because at low temperatures (17-12 degrees C) only one type of release mechanism (exocytosis) is operational and carrier-mediated uptake and release is inhibited, this temperature condition provides a method to study the mode of action of different drugs (e.g. amphetamine) and the effect(s) of certain conditions (e.g. ischemia) on the mechanisms of transmitter release, specifically whether they exert their transmitter releasing effect through an exocytotic process or through the reversed operation of plasma membrane transporter. This finding also suggests that it would be important to re-examine mechanistic conclusions based on results from electrophysiological, neurochemical and pharmacological studies that have been carried out at room temperature (approximately 20 degrees C). In particular because transmitter release associated with the action potential, diffusion, receptor kinetics, active transport in both directions (uptake and release) and the probability of transmitter release are all temperature dependent, it would seem important to carry out experiments involving these processes at physiological temperature (37 degrees C).
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PMID:Different temperature dependence of carrier-mediated (cytoplasmic) and stimulus-evoked (exocytotic) release of transmitter: a simple method to separate the two types of release. 984 Feb 27

Metallothionein III (MT-III) is a brain-specific member of the metallothionein family and binds zinc in vivo. In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III. Immunohistochemical analysis revealed that MT-III in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum. This expression pattern of MT-III was similar to that of MT-III mRNA observed by in situ hybridization studies. ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress. Immunohistochemical analysis also demonstrated intense staining in neurons in injured brain after ischemia, which distributed in the same regions as in normal brain. These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.
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PMID:Ischemia induces metallothionein III expression in neurons of rat brain. 1006 33

Rats at 4, 14, and 20 months of age were subjected to permanent occlusion of the left middle cerebral artery (MCAO) and the effects of age and ischemia assessed in tests for spatial learning (Morris' water maze), social behavior, olfactory learning, exploratory behavior, and motor function. Furthermore, the extent of ischemic damage to the brain of rats of 5 and 19 months of age was studied. An age-related decline in water-maze performance was observed, and aged rats were less agile, less explorative, and less frequently engaged in social interactions than young rats. After ischemia, mild memory impairment was observed in old rats, while changes in some exploratory behaviors were observed in young rats. Neuropathological analyses revealed a variable and limited degree of infarction in the piriform cortex and the insular cortex with no difference between age groups. In conclusion, the present study confirmed and extended current data on behavioral differences between young and old rats. MCAO had limited influence on the tested behaviors.
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PMID:Specific behavioral effects related to age and cerebral ischemia in rats. 1020 72

The antioxidant compound trans-resveratrol, is found in substantial amount in several types of red wine and is considered one of the substances responsible for the lower incidence of coronary heart diseases among regular consumers of such wines, an effect also known as the French paradox. It has also been proposed that resveratrol may have beneficial effects against neurodegenerative diseases. We report here that chronic administration of resveratrol to young-adult rats, significantly protects from the damage caused by systemic injection of the excitotoxin kainic acid, in the olfactory cortex and the hippocampus. The same treatment, however, is not able to give any significant protection in an ex vivo model of simulated ischemia on hippocampal slices in vitro. This first evidence of a partial neuroprotective action of chronic administration of resveratrol in vivo, suggests that other models of neurodegenerative injury, and in particular of excitotoxic brain damage, should be investigated in order to assess the potentiality for resveratrol to be used as a pharmacological tool for neuroprotection.
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PMID:Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. 1070 58

In several neurodegenerative diseases, iron accumulates at sites of brain pathology. Since post-mortem examination cannot distinguish whether iron accumulation caused the damage or resulted from damage, it is necessary to manipulate iron in animal and tissue culture models to assess its causal role(s). However, only in models of Parkinson's disease and of global ischemia, iron deprivation (ID) or iron-chelators have been used to protect from damage. In these studies, documentation of microgliosis was not performed even though several lines of evidence converge to suggest that activation of microglia is an important source of oxidative stress. In the kainate model of epilepsy, we found that ID protected the olfactory cortex, thalamus and hippocampus and attenuated microgliosis, whereas iron supplementation to ID rats increased damage and microgliosis in the above regions. In the hilus of the hippocampal dentate gyrus, even though no cell loss was observed, ID attenuated microgliosis and iron-supplementation increased it. Thus there is a tight relationship between iron and microgliosis. In addition, iron+zinc supplementation dramatically increased damage to hippocampal CA1 whereas zinc supplementation alone had no effect. This study demonstrates an anatomically unique interaction of iron and zinc, which may lead to new insights to neurodegeneration in epilepsy.
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PMID:Iron involvement in neural damage and microgliosis in models of neurodegenerative diseases. 1087 37

p38 has been implicated to play a critical role in regulating apoptosis in PC12 and cerebellar granule cells, and is inactivated in cultured fetal neurons in response to insulin. Though p38 is activated in microglia after ischemia, the physiological functions of p38 in the brain are not well understood. As a first step to elucidate the physiological functions of p38 in the central nervous system, we raised a polyclonal antibody against p38 and performed immunohistochemical examination to demonstrate the localization of p38 in mouse brain. Strong p38 immunoreactivity was apparent in fiber bundles including the olfactory tract, anterior commissure, corpus callosum, cingulum, internal capsule, stria terminalis, fimbria and alveus hippocampi, fornix, stria medullaris, optic chiasm and optic tract. Although similar regions were stained with both anti-p38 and anti-neurofilament antibodies, intense p38 immunoreactivity was often observed in myelin sheath-like structures but not in axons. This is the first demonstration of the localization of p38 in the central nervous system and provides an anatomical basis for understanding physiological roles of p38.
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PMID:Immunolocalization of p38 MAP kinase in mouse brain. 1113 25

Progenitor cells in the subventricular zone of the lateral ventricle and in the dentate gyrus of the hippocampus can proliferate throughout the life of the animal. To examine the proliferation and fate of progenitor cells in the subventricular zone and dentate gyrus after focal cerebral ischemia, we measured the temporal and spatial profiles of proliferation of cells and the phenotypic fate of proliferating cells in ischemic brain in a model of embolic middle cerebral artery occlusion in the adult rat. Proliferating cells were labeled by injection of bromodeoxyuridine (BrdU) in a pulse or a cumulative protocol. To determine the temporal profile of proliferating cells, ischemic rats were injected with BrdU every 4 h for 12 h on the day preceding death. Rats were killed 2-14 days after ischemia. We observed significant increases in numbers of proliferating cells in the ipsilateral cortex and subventricular zone 2-14 days with a peak at 7 days after ischemia compared with the control group. To maximize labeling of proliferating cells, a single daily injection of BrdU was administered over a 14-day period starting the day after ischemia. Rats were killed either 2 h or 28 days after the last injection of BrdU. A significant increase in numbers of BrdU immunoreactive cells in the subventricular zone was coincident with a significant increase in numbers of BrdU immunoreactive cells in the olfactory bulb 14 days after ischemia and numbers of BrdU immunoreactive cells did not significantly increase in the dentate gyrus. However, 28 days after the last labeling, the number of BrdU labeled cells decreased by 90% compared with number at 14 days. Clusters of BrdU labeled cells were present in the cortex distal to the infarction. Numerous cells immunostained for the polysialylated form of the neuronal cell adhesion molecule were detected in the ipsilateral subventricular zone. Only 6% of BrdU labeled cells exhibited glial fibrillary acidic protein immunoreactivity in the cortex and subcortex and no BrdU labeled cells expressed neuronal protein markers (neural nuclear protein and microtubule associated protein-2). From these data we suggest that focal cerebral ischemia induces transient and regional specific increases in cell proliferation in the ipsilateral hemisphere and that proliferating progenitor cells may exist in the adult cortex.
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PMID:Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. 1148 98

Adrenomedullin (AM) is a novel vasodilator peptide first purified from human pheochromocytoma by tracing its capacity to stimulate cAMP production in platelets. AM immunoreactivity is widely distributed in the central nervous system (CNS) and in the rat has been demonstrated by immunohistochemical techniques to be present in many neurons throughout the brain and spinal cord, as well as in some vascular endothelial cells and perivascular glial cells. Electron microscopy shows that the immunoreactivity is located mainly in the neuronal cytoplasm, but also occurs in the cell nucleus in some cells of the caudate putamen and olfactory tubercle. Biochemical analyses suggest that higher molecular forms, presumably precursor forms, may predominate over fully processed AM in some brain areas. The expression of AM immunoreactivity is increased in cortical neurons, endothelial cells, and perivascular processes after a simulation of ischemia by oxygen and glucose deprivation. Immunohistochemical, electrophysiological, and pharmacological studies suggest that AM in the CNS can act as a neurotransmitter, neuromodulator, or neurohormone, or as a cytoprotective factor in ischemic/hypoxic conditions, in addition to its vasodilator role.
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PMID:Adrenomedullin in the central nervous system. 1192 58

Zinc maintains a diverse array of functions in the mammalian central nervous system as a key component of numerous enzymes, via its role in the activation of transcription factors, and as a neuroregulator, modulating neuronal receptors such as N-methyl-D-aspartate and gamma-aminobutyric acid. Zinc has a dark side, however, with massive influx of Zn(2+) to neurons considered to be a key factor in neuronal death secondary to ischemia and seizure. Several different putative zinc transporters, ZnT-1-4, have recently been identified and characterized. Among them, ZnT-1 has been suggested to play a key role in reducing cellular Zn(2+) toxicity. In the present study, we describe the regional and cellular distribution of ZnT-1 in the adult mouse brain using an antibody raised against the C-terminal domain of mouse ZnT-1. The distribution of ZnT-1 was compared to that of chelatable Zn(2+), visualized by means of neoTimm histochemistry or N-(6-methoxy-8-quinolyl)-p-toluene-sulfonamide (TSQ) histofluorescence. Extracts from various brain regions specifically stained a 60-kDa peptide corresponding to the expected molecular weight of ZnT-1. The expression of ZnT-1 was highest in the cerebral cortex and cerebellum, moderate in the hippocampus, hypothalamus, and olfactory bulb, and lowest in the striatum and septum. In brain sections, ZnT-1-immunoreactive neurons, in particular principle neurons, in the somatosensory cortex, hippocampus, and olfactory bulb, were closely related to synaptic Zn(2+). Robust ZnT-1 immunoreactivity was also observed in cerebellar Purkinje cells. Although the function of the protein in these cells is unclear, in the forebrain, ZnT-1 is strikingly present in cells and regions where significant Zn(2+) homeostasis is required. This finding suggests a protective role for neuronal ZnT-1 in the context of both normal and pathophysiological activity.
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PMID:Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain. 1198 15


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