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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unilateral (50 to 118 minutes) and bilateral (2 to 33 minutes) carotid artery occlusion in gerbils resulted in two distinct types of neuronal alteration: ischemic cell change (ICC) in selectively vulnerable brain regions, and selective chromatolysis (SC) confined to the deeper layers of the cortex, the Sommer sector of zone h-1, and the paramedian region (PM) of the hippocampus. In typical SC the nucleus was eccentric and the Nissl substance was lost in the central eosinophilic cytoplasm. In electron micrographs this area of cytoplasm showed disruption of smooth and rough endoplasmic reticulum with disaggregation of polyribosomes and accumulation of mitochrondria and various dense bodies. SC was identified at 2 to 3 hours and was still recognizable at five days. When bilateral carotid artery occlusion lasted 5 to 6 minutes, SC was seen in the hippocampal Sommer sector and cerebral cortex, while ICC was restricted to the endfolium (h3-5). Unlike ICC, the frequency of SC was not related to the duration of ischemia but probably to the epileptic seizures (overt and subclinical) initiated by ischemia in the gerbil. These changes must be considered when the gerbil is employed as a model of experimental stroke.
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PMID:Selective chromatolysis of neurons in the gerbil brain: a possible consequence of "epileptic" activity produced by common carotid artery occlusion. 42 76

Understanding of the mechanisms of cell injury and cell death is fundamental to the understanding of both protection against and initiation of cell injury and cell death. We subjected primary cultures of proximal tubular epithelium (PTE) from adult rats to an exogenous oxidative stress, generated by xanthine/xanthine oxidase (X/XOD), and studied its effect on the concentration of cytosolic ionized calcium ([Ca2+]i) by means of digital imaging fluorescence microscopy (DIFM) using a cytosolic calcium probe, fura-2. Exposure to 25 mU/ml X/XOD caused notable increases in [Ca2+]i detectable within 15 sec and increasing to micromolar levels with time. Experiments with Ca(2+)-free medium containing ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) showed that the increase of [Ca2+]i was due to influx from the extracellular space. Smaller and slower increases in [Ca2+]i were seen after exposure to lower concentrations of X/XOD (5 and 10 mU/ml). PTE injury and killing were assessed by measuring the release of cytosolic lactate dehydrogenase (LDH), exclusion of trypan blue, and observation of morphologic changes. Exposures to the 25 mU/ml concentration of X/XOD caused significant LDH release after 2 hr and correlated with trypan blue staining of exposed cells. Again, lesser concentrations of X/XOD resulted in a slower release of smaller amounts of LDH, and thus delayed trypan blue staining. Cytoplasmic bleb formation was seen by phase microscopy within minutes of exposure to 25 mU/ml, followed by cell rounding, retraction, and disintegration. Transmission electron microscopy revealed a progression of changes characteristic of lethal cell injury, beginning with dilatation of the endoplasmic reticulum, detachment of ribosomes, condensation of mitochondria, and chromatin clumping and terminating with mitochondrial swelling and formation of intramitochondrial flocculent densities. These studies clearly show that notable increases of [Ca2+]i precede both sub-lethal and lethal changes in rat PTE. These results indicate that interventions designed to minimize or to accelerate calcium entry could be of importance in cell preservation or cell killing, respectively, and therefore to therapeutic strategies for myocardial infarction, stroke, or shock in the former instance and for cancers in the latter.
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PMID:Oxidative injury induces influx-dependent changes in intracellular calcium homeostasis. 177 66

Thirty three cases of pituitary adenoma were examined by MRI with 0.15 T system. Eight cases of functioning tumor showed iso-minimally low intensity, and 10 cases of non-functioning tumor did slightly-markedly low intensity on IR image. Functioning tumor cells contain well-developed rough-surfaced endoplasmic reticulum, Golgi complexes and numerous secretary granule, so that bound water more increases and T 1 relaxation time less prolongs in functioning tumor than in non-functioning tumor. Two cases of functioning tumor disclosed slightly low intensity on IR image because of its poor stroma. It is necessary to know the exact bleeding time so as to measure the signal intensity in pituitary apoplexy case. Microadenoma appeared spotty hypointensity and upward convexity of superior surface of the gland on IR image.
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PMID:[Magnetic resonance image of pituitary adenoma--comparison of functioning tumor and non-functioning tumor]. 250 33

Cholera toxin subunit B suppressed the proliferation of cultured vascular smooth muscle cells from the thoracic aorta of Wistar-Kyoto rats (WKY), stroke-resistant spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). Since cholera toxin subunit B did not stimulate cyclic AMP accumulation in vascular smooth muscle cells, the effect of cholera toxin subunit B might be due to another mechanism. Cholera toxin subunit B bound to the surface of vascular smooth muscle cells and was rapidly incorporated into them. The morphological structure of vascular smooth muscle cells was transformed from the synthetic type to the non-synthetic type, in which microfilaments and intermediate filaments were abundantly formed, while rough endoplasmic reticulum was decreased after CTB treatment.
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PMID:A new approach to the prevention of hypertensive cardiovascular diseases by controlling the proliferation of vascular smooth muscle cells. 324 Dec 10

Cells react to physical (e.g., heat) or chemical (e.g., anoxia, low pH) stressors, mounting a stress (heat-shock) response. Most genes are turned down or off, while a few are activated. The latter encode the stress or heat-shock proteins (Hsps), whose levels increase in stressed cells. Various Hsps are molecular chaperones. These, and other molecular chaperones that are not Hsps, help the other cellular proteins to achieve their native state (correct folding or functional conformation), reach their final destination (e.g., the endoplasmic reticulum or the mitochondria), resist denaturing by stressors, and regain the native state after partial denaturation. Thus the Hsps and molecular chaperones occupy the stage's center whenever and wherever there is cellular and tissue injury caused by local or systemic stressors via protein damage. This feature, their participation in protein folding and transport, and their evolutionary conservation within the three phylogenetic domains, strongly suggest a vital role for Hsps and molecular chaperones. Their importance in pathogenesis, and as diagnostic markers and prognostic indicators, is beginning to be appreciated. The role of Hsps and molecular chaperones in cell recovery from injury by a variety of noxae of clinical and surgical relevance is also being assessed. Consequently, the potential of these molecules (and corresponding genes) as targets for treatment or as therapeutic tools is emerging and is being explored. Stroke, myocardial infarction, inflammatory syndromes, infectious and parasitic diseases, autoimmune disorders, cancer, and aging are but some examples of conditions in which Hsps and molecular chaperones are being scrutinized. The era of Hsp and molecular chaperone pathology has dawned. It is likely that genetic and acquired defects of Hsp and molecular chaperone structure and function will be identified, and will play a primary, or auxiliary but determinant, role in disease.
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PMID:Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics. 766 7

To obtain information about changes of basic fibroblast growth factor (bFGF) in the brain under a chronic hypertensive condition, we immunohistochemically studied the distribution and level of bFGF in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). The advanced cerebral lesions in SHRSPs demonstrated massive bleeding, cavity formation and diffuse degeneration of the white matter, whereas the early changes were petechiae, edema and massive glial accumulation around fibrin deposition containing necrotized microvessels. In the control normotensive rats, immunoreactivity for bFGF was demonstrated in nerve cells, especially in selective neuronal populations, ependymal cells and epithelial cells of the choroid plexus, while there was almost no reactivity in astrocytes. In SHRSPs, on the other hand, there was marked immunoreactivity in the densely accumulated reactive cells, particularly astrocytes, in and around cerebral cortical lesions. Slightly increased reaction for bFGF was found in the nerve cells around lesions. Astrocytes in the subcortical white matter on both ipsi- and contralateral sides of the cortical lesion also showed immunoreactivity for bFGF. The location of increased bFGF expression in SHRSPs corresponded very well with the site of extravasated plasma fluid demonstrated by anti-fibrinogen antibody. Electron microscopically, bFGF was shown in astrocytes along the rough endoplasmic reticulum, suggesting that the growth factor was produced in the cells and not taken up from the surroundings. These findings indicate the possibility that edema and the simultaneously generated free radicals or some extravasated plasma components express bFGF in astrocytes and probably in nerve cells, and that the thus expressed bFGF plays some role in the sequence of developmental events of hypertensive cerebral lesions.
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PMID:Increased basic fibroblast growth factor immunoreactivity in the brain of stroke-prone spontaneously hypertensive rats. 794 75

1. To obtain information about changes of basic fibroblast growth factor (bFGF) in the brain in chronic hypertension, we immunohistochemically studied the distribution and level of bFGF and its receptor in the brain of stroke-prone spontaneously hypertensive rats (SHRSP). 2. In the control normotensive rats, immunoreactivity for bFGF was demonstrated in nerve cells, while there was almost no reactivity in astrocytes. 3. In SHRSP, there was a marked immunoreactivity in the densely accumulated reactive cells, particularly astrocytes, in and around cerebral cortical lesions. Slightly increased reaction for bFGF was found in the nerve cells around lesions. Astrocytes in the subcortical white matter on both ipsi- and contralateral sides of the cortical lesion also showed immunoreactivity for bFGF. The location of increased bFGF expression in SHRSP corresponded very well with the site of extravasated plasma fluid demonstrated by anti-fibrinogen antibody. Electron microscopically, bFGF was shown in astrocytes along the rough endoplasmic reticulum suggesting the growth factor to be produced in the cells and not to be taken up from the surroundings. Expression of FGF-receptor was also demonstrated in reactive astrocytes in the oedematous cortical portion around lesion and in the oedematous subcortical white matter. 4. These findings indicate the possibility that oedema and the simultaneously generated free radicals or some extravasated plasma components express bFGF in astrocytes and probably in nerve cells as well as FGF-receptor in astrocytes, and that the thus expressed bFGF and its receptor play some role in the sequence of developmental events of hypertensive cerebral lesions.
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PMID:Increased immunoreactivities for the basic fibroblast growth factor and its receptor in astrocytes at the site of cerebral lesions and oedematous change in SHR. 907 83

The minireview summarizes data documenting that pyridoindole stobadine (STB) may protect nervous structures against oxidative stress. This was demonstrated by the impairment of synaptic transmission in hippocampal slices and sympathetic ganglia exposed to hypoxia/reoxygenation (H/R) in vitro as well as by survival of rats and dogs exposed to brain ischemia/reperfusion (I/R) in vivo. The STB effect was linked mostly to its free radical scavenging and antioxidant properties. STB seems to act primarily on phospholipids, thus protecting the integrity and function of somatic membranes in neurons as well as those in subcellular organelles, such as mitochondria and endoplasmic reticulum. STB prevented damage to Ca2+ sequestering systems in endoplasmic reticulum and synaptosomes induced by lipid peroxidation initiators. It was found to diminish changes in NMDA and adrenergic alpha1-receptors evoked in the brain by I/R or H/R. The compound prevented total thiols, participating in tissue antioxidative protection, from decreasing in brain under these conditions. It readily penetrates into both the hydrophilic and the hydrophobic compartments of the CNS. Data were obtained indicating that in I/R, protection of structures such as brain-blood vessels, endothelium, and/or erythrocytes may participate in the STB effect, besides the direct protection of nervous tissue. STB may be characterized as a potential protectant of the CNS in diseases in which oxidative injury may play an important role, for example, stroke, neurotrauma, chronic brain ischemia, or some neurodegenerative diseases. Its molecule could provide a useful model in the further search for novel compounds with even more pertinent pharmacological and pharmacokinetic profiles.
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PMID:Neuroprotection by the pyridoindole stobadine: a minireview. 909 73

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).
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PMID:Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). 1006 65

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Studies of cultured neural cells suggest that PS1 mutations result in perturbed cellular calcium homeostasis and may thereby render neurons vulnerable to apoptosis. In light of evidence that metabolic impairment plays a role in AD, that cerebral ischemia may be a risk factor for AD, and that individuals with AD have increased morbidity and mortality after stroke, we examined the impact of a PS1 mutation on neuronal vulnerability to ischemic injury. We report that the extent of brain injury after focal cerebral ischemia reperfusion is increased, and behavioral outcome is worsened, in PS1 mutant knock-in mice compared to wild-type mice. Cultured cortical neurons from PS1 mutant mice exhibit increased vulnerability to glucose deprivation and chemical hypoxia compared to their wild-type counterparts. Calcium imaging studies demonstrated enhanced elevation of intracellular calcium levels after glucose deprivation and chemical hypoxia in neurons from PS1 mutant mice. Agents that block calcium release from IP(3)- and ryanodine-sensitive stores (xestospongin and dantrolene, respectively) protected against the endangering action of the PS1 mutation. Our data suggest that presenilin mutations may promote neuronal degeneration in AD by increasing the sensitivity of neurons to age-related ischemia-like conditions. The data further suggest that drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients.
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PMID:Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis. 1066 26


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