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)

We examined the changes in immunoreactivity of microtubuli-associated protein (MAP) 2 in dendrites by immunohistochemical analysis following 20 min of cerebral ischemia in the rat. A decrease of immunoreactivity of MAP 2 in dendrites in the CA1 subfield of the hippocampus was observed on days 3 and 7 but not on day 1 after ischemia. Early destructive changes of this protein were not observed, a finding which was confirmed by polyacrylamide gel electrophoresis analysis. We elucidated one factor which indicated that destruction of the dendrites of CA1 pyramidal neurons would not take place any earlier than the destruction of the neurons themselves after ischemia in rats.
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PMID:Absence of early destructive changes of cytoskeletal proteins after transient ischemia in the rat. 152 Nov 63

Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min) and allowed to recover for 3 h, 24 h, 2 days or 14 days. Consecutive tissue sections were stained with antibodies against alpha-fodrin, the 150 kDa breakdown product of alpha-fodrin (FBDP, marker of calpain proteolysis) or microtubule associated protein 2 (MAP 2, marker of dendrosomatic neuronal injury). Cortical tissue pieces were subjected to Western blotting using the antibody against the FBDP. Areas with brain injury displayed a distinct loss of MAP 2 which clearly delineated the infarct. FBDP accumulated in injured and borderline regions ipsilaterally and a less conspicuous, transient increase in FBDP also occurred in the contralateral hemisphere, especially in the white matter. A reciprocal staining pattern could be seen in the cerebral cortex, i.e. loss of MAP 2 and accumulation of FBDP, most pronounced 14 days after the insult. Fodrin and MAP 2 are known calpain substrates, and degradation of these proteins preceded neuronal degeneration, indicating that these proteases may be involved in the early events triggering the cascades leading to neuronal death.
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PMID:Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia. 758 14

One of the most prominent phenomena that occurs during the early phase of cerebral ischemia has been shown to be the immunohistochemical collapse of cytoskeletal proteins. Among these, microtubule-associated protein 2 (MAP 2) has been shown to be vulnerable to ischemic injuries. In order to select a suitable volatile anaesthetic from the standpoint of cytoskeletal protein breakdown during cerebral ischemia, we compared the effect of isoflurane, halothane and sevoflurane on MAP 2 degradation during 20 min of forebrain ischemia in the rat. Under 1 MAC of three volatile anesthetics, forebrain ischemia was induced by the occlusion of the bilateral common carotid artery combined with a lowering of mean arterial pressure to 50 mmHg. Immediately after cerebral ischemia, four regions of the brain, the frontoparietal cortex, brainstem, hippocampus and cerebellum, were removed separately and homogenized. Subsequently, MAP 2 from each region was quantitatively measured using an enzyme-linked immunosorbent assay. MAP 2 in the frontoparietal cortex and hippocampus was significantly protected from degradation with isoflurane anaesthesia more than with halothane and sevoflurane anaesthesia.
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PMID:[Effects of volatile anesthetics on microtubule-associated protein 2 degradation during forebrain ischemia in the rat]. 783 96

The effects of prostaglandin E1 (PGE1) on transient forebrain ischemia were studied in the gerbil. The animals were randomly divided into six groups of 6 each according to the method of administration as follows: group 1, no administration; group 2, subcutaneous administration with 5 ml.kg-1 of physiological saline, 30 min prior to ischemia; group 3, the same method with 3 mg.kg-1 of PGE1; group 4, 3 mg.kg-1 of PGE1, during 24 hours (12 hours prior to ischemia, and 12 hours following ischemia); group 5, 3 mg.kg-1 of PGE1, during 96 hours (12 hours prior to ischemia and 84 hours following ischemia); and group 6, sham operation. They were anesthetized with isoflurane and transient forebrain ischemia was induced by occluding bilateral common carotid arteries for 5 min. The extracranial electroencephalogram (EEG) was recorded from the electrodes placed at the vertex. During the experimental procedures, temperatures at tympanic membrane and rectum were maintained at 37.0 +/- 0.2 degrees C by means of a heating mat and control of the air temperature in all groups. After 6 days of survival, they were sacrificed, and the brain tissues were fixed for the immunohistochemical and histopathological analyses. The hippocampal CA 1 regions were stained for monoclonal anti microtubule-associated protein 2 (MAP 2), and hematoxylin and eosin. In the 4th group, EEG recovery was recognized earlier than the other groups. Immunoreactivities for MAP 2 and the number of surviving pyramidal cells after ischemia in the CA 1 regions were also well maintained. These results suggest the PGE1, has protective effects against degradation of cytoskeletal proteins and delayed neuronal death in the gerbil, and it might be due to direct protective action of cell membrane in addition to its microcirculatory improvement.
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PMID:[Effects of prostaglandin E1 on transient forebrain ischemia, especially in hippocampal CA 1 regions of the gerbil]. 893 17

In a situation with normal CBF and without increased energy utilization, increased glucose utilization (CMRglc) can be a sign of impaired mitochondrial metabolism, which may be an early step in the injury cascade during reperfusion after hypoxia-ischemia (HI). Seven-day-old rats underwent unilateral carotid artery ligation and 70 minutes of HI. At 3, 6, 12, 24, and 48 or 72 hours after the insult, the CMRglc was measured by the 2-deoxyglucose method, and CBF by the iodoantipyrine method. These were compared with hematoxylin-eosin staining and microtubule-associated protein 2 (MAP 2) immunostaining in adjacent sections. In the ipsilateral hemisphere, there appeared regions with increased CMRglc compared with the contralateral hemisphere 3 to 12 hours after HI that also showed partial loss of MAP 2 immunostaining and early ischemic changes. These areas receded, leaving central glucose hypoutilizing areas with complete loss of MAP 2 immunostaining and histologic infarction, surrounded by only a rim of tissue with increased CMRglc. At 24 and 72 hours after the insult, no regions with increased CMRglc remained. Despite loss of MAP 2 immunostaining and histologic signs of infarction at 24 hours, cortical CBF was not reduced until 48 hours after HI, whereas the CBF in the caudate-putamen already was decreased compared with the contralateral side at 3 hours after HI. In conclusion, early reperfusion is characterized by glucose hyperutilizing areas in the cerebral cortex, followed by a secondary phase with low CMRglc and infarction.
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PMID:Temporal changes of regional glucose use, blood flow, and microtubule-associated protein 2 immunostaining after hypoxia-ischemia in the immature rat brain. 946 66

Excitatory amino acids may promote microtubular proteolysis observed in ischemic neuronal degeneration by calcium-mediated activation of calpain, a neutral protease. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. Spontaneously hypertensive rats were treated with 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)quinoxaline (NBQX), a competitive antagonist of the neuronal receptor for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or cis-4-[phosphono-methyl]-2-piperidine carboxylic acid (CGS 19755), a competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor. After treatment, all animals were subjected to permanent occlusion of the middle cerebral artery for 6 or 24 h. Infarct volumes measured in animals pretreated with CGS 19755 after 24 h of ischemia were significantly smaller than those quantified in ischemic controls. Rats pretreated with NBQX showed partial amelioration of cytoskeletal injury with preserved immunolabeling of microtubule-associated protein 2 (MAP 2) at 6 and 24 h and reduced accumulation of calpain-cleaved spectrin byproducts only at 6 h. Prevention of cytoskeletal damage was more effective after pretreatment with CGS 19755, as shown by retention of MAP 2 immunolabeling and significant restriction of calpain activity at both 6 and 24 h. Preserved immunolabeling of tau protein was observed at 6 and 24 h only in animals pretreated with CGS 19755. Western analysis performed on ischemic cortex taken from controls or rats pretreated with either NBQX or CGS 19755 suggested that loss of tau protein immunoreactivity was caused by dephosphorylation, rather than proteolysis. These results demonstrate a crucial link between excitotoxic neurotransmission, microtubular proteolysis, and neuronal degeneration in focal cerebral ischemia.
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PMID:Glutamate receptor antagonists inhibit calpain-mediated cytoskeletal proteolysis in focal cerebral ischemia. 981 16

Caspase-3 has been identified as a key protease that, by targeting a limited number of proteins, can disrupt essential homeostatic processes and initiate an orderly disassembly of cells, including degradation of genomic DNA. We demonstrate the usefulness of an antibody specific for activated caspase-3 in a model of neonatal rat hypoxia-ischemia (Hl) and correlate the spatial and temporal activation of caspase-3 with three different markers of DNA damage and with the loss of a neuronal marker [microtubule-associated protein 2 (MAP 2)]. An oligonucleotide hairpin probe (HPP) with one base overhang in the 3' end displayed a close colocalization with caspase-3 activation at 3 h post-Hl, whereas terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) appeared later (24 h post-Hl). A monoclonal antibody against single-stranded DNA appeared to stain an entirely different population of cells, not positive for active caspase-3, HPP, or TUNEL at this time point. After 24 h of reperfusion, however, when cellular injury is extensive, all markers stained a large number of cells with a high degree of colocalization, and all markers delineated regions with loss of MAP 2. We conclude that the HPP shows the best correlation with pathological caspase-3 activation in this model.
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PMID:Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia. 1089 60

2-(3',5'-Dimethoxybenzylidene) cyclopentanone (DMBC) is a novel small-molecule compound synthesized by our group. Here, we found that in rat models of permanent middle cerebral artery occlusion (pMCAO), intraperitoneal injection (ip) of DMBC at 1h after ischemia reduced infarct volume, improved neurological deficits and increased the protein levels of microtubule-associated protein 2 (MAP 2) and glial fibrillary acid protein (GFAP) in the ischemic cortex. Post-treatment of DMBC still produced neuroprotective effects even when administered at 6h after ischemia. In the oxygen-glucose deprivation (OGD)-induced astrocytes or HT22 cell injury, DMBC treatment decreased the OGD-induced lactate dehydrogenase (LDH) leakage and increased the GFAP levels in astrocytes. In addition, Annexin-V-Fluos staining analysis revealed that DMBC treatment attenuated both OGD-induced apoptosis and necrosis in astrocytes. Western blotting analysis showed DMBC treatment inhibited the ischemia or OGD-induced increases in active cathepsin B in the ischemic cortex or in astrocytes or HT22 cells. Immunofluorescence analysis demonstrated that DMBC treatment blocked the ischemia or OGD-induced release of cathepsin B from the lysosomes into the cytoplasm in the ischemic cortex or in astrocytes or HT22 cells. Taken together, our results indicate that DMBC can offer neuroprotective effects against cerebral ischemia with an extended therapeutic window and its mechanism might be associated with inhibition of the cathepsin B activation.
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PMID:2-(3',5'-Dimethoxybenzylidene) cyclopentanone, a novel synthetic small-molecule compound, provides neuroprotective effects against ischemic stroke. 2665 21