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

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. In two studies within the hippocampal formation (HF), CGRP-like immunoreactivity (CGRP-LI) was increased in the inner molecular layer of the dentate gyrus after adrenalectomy and in mossy cells after colchicine-induced destruction of granule neurons. Given the increase in CGRP-LI following damage to the granule cell region of the HF, we investigated another trauma model, ischemia, that targeted different areas of the HF, CA1 region, and subiculum to ascertain the regional expression of this peptide after insult. Following ischemia, light microscopic evaluation showed CGRP-LI in basket cell-like neuronal perikarya within the dorsal subiculum and CA1 region of the hippocampus and in varicose fibers within the CA2 region of the hippocampus. Control rats rarely expressed CGRP-LI within neurons in these regions. In ischemic brains, double-labeled immunocytochemistry with antibodies to various neural markers demonstrated co-localization of CGRP-LI primarily within surviving subicular and CA1 cells resembling interneurons containing parvalbumin-LI or calbindin-LI. Electron microscopic analysis of the CA1 region from ischemic brains showed that CGRP-LI was contained in terminals with numerous small synaptic vesicles that formed symmetric synapses with perikarya and large dendrites of pyramidal cells, some of which were degenerating. Collectively, the data from this study and our previous study indicate that damage induces CGRP-LI expression in interneurons and nonprincipal cells in the area of damage, and we hypothesize that CGRP expression in surviving neurons within damage-related regions of the hippocampus is likely to be an important, and possibly a protective, component of the response of the nervous system to injury.
 ...
PMID:Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal neurons following ischemia: a putative regional modulator of the CNS injury/immune response. 952 88

Studies in adult animal models of transient cerebral hypoxia-ischemia (HI) and ischemia suggest that morphologic evidence of neuronal death in some regions such as striatum appears early, while in other regions such as cerebral cortex and CA1 region of hippocampus it is delayed for few days and is referred to as delayed neuronal death (DND). Moreover, in some regions such as CA2/CA3 early 'reactive' neuronal changes occur that are potentially reversible. The aim of this study was to determine whether such changes may also occur in the developing brain. To that end, unilateral cerebral HI was produced in postnatal rats of 13, 21, and 30 days (p13, p21, p30) by right common carotid artery ligation and hypoxemia (breathing 8% O2), and their brains were examined at 24 h, 36 h, 72 h, and 96 h of recovery. The results suggest that: (i) DND is present in developing brain, but its regional distribution varies with animals' age. In cerebral cortex, it is more pronounced in p30 rats than in younger animals. In hippocampus, comparison of lesions of similar severity at different age groups shows a more pronounced DND in CA2/CA3 region of p13 rats than in older animals, but no significant differences exist in the degree of DND in CA1 neurons among different age groups. (ii) 'Reactive' neuronal changes characterized by reduction in Nissl staining and acidophilia of neuronal perikaryon with minimal nuclear abnormality are present at 24 h of recovery. These changes in some regions, such as in CA1 and cortex, progress to neuronal death, while in other regions such as in CA2/CA3 are potentially reversible. (iii) Recovery of reactive neurons in CA2/CA3 region is age dependent in that there is significant recovery in the older age groups, but not in p13 rats. The pathogenetic mechanisms of the reactive neuronal changes, the chain of events leading to DND or neuronal recovery, and the influence of age in these processes remain to be elucidated.
 ...
PMID:Temporal evolution of neuronal changes in cerebral hypoxia-ischemia in developing rats: a quantitative light microscopic study. 972 65

Gerbils aged 3 months and 24+ months were subjected to 5 min of global forebrain ischemia and tested in a radial arm maze (1 trial/day, 50 days). Compared with age-matched, sham-operated controls, ischemic animals were impaired on measures of both working and reference memory. Aged animals were impaired on working memory, but not on reference memory, compared with their younger counterparts. Hippocampal CA1 and CA2 regions were significantly and comparably damaged in the 2 ischemic groups but were unaffected by aging. The results suggest that aging and ischemia have functionally similar effects on working memory, but the 2 processes differentially impact reference memory.
 ...
PMID:Aging and ischemia in gerbils impair spatial memory performance. 973

The recent advances in the histopathology of ischemia have set forth new proposals, particularly in regard to excitotoxicity by the glutamate receptor, NMDA. The participation of the nitric oxide (NO) in normal and pathological conditions and its relationship with toxicity in ischemia, suggest new alternatives for the modulation of the NMDA receptor REDOX site through its pharmacologic manipulation. This event would potentially limit the consequences of the activation-calcium flow and the production of peroxoinitrite during the ischemic phenomenon. The present work delivers two proposals: 1) A modified technique to the ones that have been described, of endovascular, without craniectomy, for experimental cerebral ischemia in Wistar rats, and with particular harmful effect upon the hippocampus. 2) It promotes the use of nitrates as an additional alternative to other elements, in order to restrict excitotoxicity in the described experimental cerebral ischemia, and paying attention to CA1-CA2 of the hippocampus. This area, specially sensitive to hypoxia-ischemia, offers an excellent study option for focal, experimental, cerebral ischemia associated with toxicity mediated by excitatory amino acids, since it stores an important concentration of NMDA receptors (R1/R2 A) as well as endothelial nitric oxide synthase. Our parameters are supported by quantitative-qualitative cell analysis, and not by the extension of the stroke which offers a more objective perspective upon the assessment of the focal ischemic event. By means of this technique, these results confirm the extent of the ischemic injury to the cell at the level of the hippocampus compared to a control/basal group, P = 0.0006. Furthermore, it suggests a neuroprotective effect of isosorbide dinitrate since it preserves the viable cells, and limits the appearance of hypoxic-ischemic cells at the hippocampus when the middle cerebral artery (MCA) is occluded endovascularly, as compared to the animals with no treatment P = 0.0080. However, other research lines are needed to compare the efficacy of this present work with other therapeutic proposals.
 ...
PMID:Neuroprotection in selective focal ischemia in rats by nitrates, an alternative redox manipulation on nitric oxide: experimental model. 980 40

The development of transgenic mice has led to an increase in the use of mice as models for human disease. We hypothesized that the degree of brain damage sustained by animals in a neonatal mouse model of hypoxia-ischemia depends on the strain used. We compared three strains of mice commonly used to generate transgenic strains (C57Bl/6, 129Sv and CD1), as well as three hybrids of these strains (C57Bl/6x129Sv, CD1xC57Bl/6, and CD1x129Sv). At postnatal day 7 (P7), pups were subjected to a modified Vannucci procedure for hypoxia-ischemia as follows: permanent ligation of right common carotid artery under halothane anesthesia, 2-h recovery period, exposure to 8% oxygen at 37 degreesC for varying durations (30, 60 or 90 min). After 5 days, animals were perfused with 4% paraformaldehyde, brains were removed, postfixed and examined histologically with cresyl violet and Perl's iron stain to assess the degree of damage. Damage was assessed blindly using a score ranging from 0 (none) to 3 (infarct) in eight regions (ant-, mid-, and post- cortex, CA1, CA2, CA3 and dentate gyrus of the hippocampus, and striatum). We found significant differences in susceptibility to brain damage and mortality depending on the strain used. While determining the maximal degree of injury with the least amount of mortality for each strain, it was found that some strains (CD1) are particularly susceptible to brain damage in this model, while others (129Sv) are resistant.
 ...
PMID:Strain-related brain injury in neonatal mice subjected to hypoxia-ischemia. 981 71

The aim of the work was to evaluate the effect of CoQ10 (10 mg/kg body weight) on the morphological changes in the rat brain after the Et-1 induced cerebral ischemia. Selective necrotic foci and dark neurons were observed in the cerebral cortex, hippocampal CA1, CA2 sectors and dentate gyrus after the administration of Et-1. Around the necrotic foci, glycogen was deposited 24 hours after the ischemic hypoxia. It seems that histopathological changes evoked by Et-1 indicate the complicated mechanism connected with ischemia. After treatment with CoQ10 only sparse neuronal changes were observed. CoQ10, known oxygen-derived free radicals scavenger diminished neuronal damage in the cerebral cortex and in the hippocampus.
 ...
PMID:Evaluation of morphological changes after treatment with coenzyme Q10 (CoQ10) in endothelin-1 induced experimental ischemia in the rat. 983 95

The hippocampal formation of Mongolian gerbils expresses high amounts of atypical angiotensin II type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific [35S]-labeled riboprobes and by receptor autoradiography using [125I]Sarcosine1-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidal cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfields, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression.
 ...
PMID:Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation. 988 9

Apolipoprotein E (apoE) influences the response to and outcome from brain injury possibly through alterations in neuronal repair mechanisms. This study aimed to determine alterations in neuronal and glial apoE after brain injury in patients and sought to determine whether possession of an apoE-epsilon4 allele influences the degree of apoE immunoreactivity or the degree of neuronal damage following brain injury. ApoE immunoreactivity and neuronal damage were semiquantitatively assessed in the temporal lobe of a group of controls (n = 44) and in a group of patients who had an episode of global ischemia and subsequently died (n = 58, survival ranged from 1 hour to 3 months). There was a significant degree of neuronal damage in all hippocampal sectors and in the neocortex of the global ischemia group compared with controls (p < 0.0001). Glial apoE immunoreactivity was significantly increased in hippocampal sectors (CA1, CA2, CA3/CA4, dentate fascia) in the global ischemia group compared with controls (p < 0.01). Neuronal apoE immunoreactivity was significantly increased in all hippocampal sectors (CA1, CA2, CA3/CA4, dentate fascia) and in the neocortex of the global ischemia group compared with controls (p < 0.0001). There was a significant and positive association between the degree of neuronal apoE immunoreactivity and the degree of neuronal damage in the global ischemia cases (r2 = 0.691, p < 0.001) and there was not an association in the control group. Possession of an apoE-epsilon4 allele did not influence the degree of neuronal or glial apoE immunoreactivity or the degree of neuronal damage in the global ischemia cases or the controls. The data indicate apoE is markedly increased in neurons and glia following brain injury. In this study, apoE genotype did not appear to influence neuronal damage, glial apoE or intraneuronal apoE following injury
 ...
PMID:Influence of apolipoprotein E genotype on neuronal damage and apoE immunoreactivity in human hippocampus following global ischemia. 1019 14

Heat shock proteins (HSPs) induced by brain ischemia may play an important role in neuroprotection from neuronal degeneration. In this study, we examined the cerebral blood flow (CBF) threshold to produce regional differences in HSP72 induction after transient forebrain ischemia in spontaneously hypertensive rats (SHRs). Female SHRs were subjected to 20 min of cerebral ischemia induced by bilateral carotid artery occlusion. The CBF was measured by laser Doppler flowmetry. At forty-eight hours after cerebral ischemia and reperfusion, the rats were decapitated and the brains were removed. Specific areas (hippocampal CA1, CA2-3, dentate gyrus, dorsolateral and ventromedial striatum, and parietal cortex) were thereafter dissected from the brain. The amounts of HSP72 in these samples were determined using Western blot analysis. In the hippocampus, HSP72 was induced when the CBF decreased to less than 18-25% of the resting level. The mean values of HSP72 produced in the CA1 area, CA2-3 area, and the dentate gyrus following ischemia and reperfusion treatment were 4.44 +/- 1.43 (+/-SD) ng/microg protein, 3.51 +/- 0.72 ng/microg protein and 3.77 +/- 1.05 ng/microg protein, respectively. In the parietal cortex, the amount of HSP72 induction was less pronounced (2.55 +/- 0.40 ng/microg protein), while HSP72 was hardly detected at all in the striatum, even under conditions of very severe CBF reduction and reperfusion. We demonstrated the existence of both a CBF threshold (i.e., approximately 20% of the resting level) for HSP72 induction and regional heterogeneity for the induction of HSP72 protein.
 ...
PMID:Cerebral blood flow threshold and regional heterogeneity of heat shock protein 72 induction following transient forebrain ischemia in rats. 1034 97

There is much evidence to suggest that ischemic injury occurs during the reperfusion phase of ischemia-reperfusion insults, and that the injury may be due to reactive-oxygen-species (ROS)-mediated oxidative events, including lipid peroxidation and DNA damage. However, oxidative DNA damage has until now not been examined in situ. In the present study, we report for the first time observation of cell type- and region-specific oxidative DNA damages in 5 min transient ischemic model by immunohistochemical methods, using monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA product. The cell types containing 8-OHdG immunoreactivity were neurons, glia and endothelial cells in the hippocampus. The 8-OHdG immunoreactivity was present in the nucleus but not the cytoplasm of these cells. The level of 8-OHdG in CA1 increased significantly (P<0.05) at the end of 30 min after ischemia, but there was no increase within CA2 and CA3 areas. The 8-OHdG levels in the hippocampus increased significantly (about fourfold) after 3 h of reperfusion and remained significantly (P<0.01) elevated for at least 12 h. At 4 days after ischemia, 8-OHdG levels in the CA2 and CA3 areas decreased to levels of the sham without neuronal loss, while disappearance of 8-OHdG immunoreactivity in the CA1 coincided with neuronal death in this area. These findings strongly suggest that ischemia-induced DNA damage evolves temporally and spatially, and that oxidative DNA damage may be involved in delayed neuronal death in the CA1 region.
 ...
PMID:Immunohistochemical detection of oxidative DNA damage induced by ischemia-reperfusion insults in gerbil hippocampus in vivo. 1041 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>