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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurobehavioral teratogenesis caused by prenatal nicotine exposure is associated with deficiencies in brain cell numbers that reflect, in part, effects on cell replication but that also involve delayed cell loss. In the current study, pregnant rats were given nicotine by implanted minipump infusion either from gestational days 4-12 or 4-21 and fetal and neonatal brain regions were examined for expression of the mRNA encoding c-fos, a nuclear transcription factor that becomes chronically elevated when cell injury or apoptosis are occurring. Fetuses exposed to nicotine on gestational days 4-12 did not show elevations of c-fos mRNA on gestational day 18 whereas animals undergoing exposure through day 21 did. In the latter group, elevated c-fos expression was still present on postnatal day 2 despite the cessation of nicotine exposure on gestational day 21. In contrast to the elevation of c-fos seen with prenatal nicotine, postnatal nicotine injections given to 2-day-old rats did not cause acute stimulation of c-fos expression. The ability of injected nicotine to evoke acute rises in c-fos emerged by postnatal day 8 and initially displayed regional specificity paralleling the concentration of nicotinic cholinergic receptors. With increasing maturity, regional selectivity of the c-fos response to acute nicotine was lost, consistent with indirect actions that could be mediated through nicotine-induced hypoxia/ischemia. These results indicate that prenatal nicotine exposure causes chronic elevations of c-fos expression in fetal and neonatal brain that are distinguishable from the later onset of the ability of acute nicotine to cause short-term stimulation of c-fos. The critical period and dose threshold for these effects correspond to those of subsequent cell damage and cell loss identified in previous studies with fetal nicotine exposure. Given that chronic elevations of c-fos are known to be associated with cell injury and to evoke apoptosis in otherwise healthy cells, these results suggest that prenatal nicotine exposure evokes delayed neurotoxicity by altering the program of neural cell differentiation, and that elevated c-fos expression provides an early marker of the eventual deficits.
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PMID:Cryptic brain cell injury caused by fetal nicotine exposure is associated with persistent elevations of c-fos protooncogene expression. 909 43

We have reported that basic fibroblast growth factor (bFGF) prevents retrograde degeneration of thalamic neurons after middle cerebral artery (MCA) occlusion. To identify the protective mechanism of bFGF, we examined bFGF mRNA expression in a model of transient focal ischemia with in situ hybridization. Compared to c-fos, c-jun, and hsp 70 mRNA expression, upregulation of the bFGF mRNA expression was delayed until 6 h after reperfusion. By 12 h, bFGF mRNA was markedly induced in the peri-infarcted cortex, cingulate cortex, and peri-infarcted white matter. At 24 h and 2 days the induction of bFGF mRNA in these regions persisted, and disappeared by 5 day. The quantitative assessment of bFGF mRNA expression revealed that optical density ratios of the cingulate gyrus and the caudoputamen were significantly higher at 12 h, 24 h, and 2 d after reperfusion than those in sham controls. Microscopic observation indicated bFGF mRNA signals were present in several types of cortical cells, including neurons and nonneuronal cells. Since intrinsic bFGF, released from the damaged tissue, can influence the healing response through receptors upregulated by injury, it is reasonable that this pattern of bFGF mRNA expression parallels the bFGFR mRNA expression previously reported.
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PMID:Expression of basic fibroblast growth factor mRNA after transient focal ischemia: comparison with expression of c-fos, c-jun, and hsp 70 mRNA. 915 69

1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.
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PMID:The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. 918 94

The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia. In this study, the expression of six zinc finger IEG was examined using in situ hybridization in adult rats after middle cerebral artery occlusion (MCAO) with the suture model. NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 mRNA were all induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO. The cortical induction for most of the genes was greatest in the anterior cingulate and the anterior cerebral artery (ACA) and middle cerebral artery (MCA) transition zone. All of the zinc finger IEG were induced at 1 hour in all regions of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamus. Within areas of infarction, the basal IEG mRNA expression, and expression of the housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours after the ischemia. Immediate early gene expression outside areas of infarction returned to control levels in most brain regions by 24 hours except for egr-3, which continued to be induced in the MCA/ ACA transition zone for 24 hours, and NGFI-A, which continued to be expressed in specific regions of the thalamus for 72 hours. The induction of these IEG in the cortex is likely caused by ischemia-induced cortical spreading depression, with the hippocampal and thalamic IEG induction being caused by activation of efferent cortical pathways to these regions. The prominent induction of NGFI-B, NGFI-C, egr-2, and egr-3 in the anterior cingulate cortex, the ACA/MCA transition zone, and medial striatum could reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression observed in thalamus in this study, and in CA1 of hippocampus after global ischemia in the gerbil in a previous study, suggests that the prolonged NGFI-A, expression could be the result of or the cause of the delayed cell death. Prolonged NGFI-A expression, like c-fos and c-jun, seems to provide a marker for slowly dying neurons.
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PMID:Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion. 923 20

The expression of immediate early genes (IEG) has been documented in the brain after various kinds of insults such as ischemia and hypoxia. To determine whether acute carbon monoxide intoxication (ACOI) might trigger IEG expression, adult ddY mice were subjected to carbon monoxide exposure at a rate of 30 mL/min for 35 seconds. The levels of NGFI-B, c-fos, and c-jun mRNA were determined by Northern blot analysis. A time-course study in the cerebral cortex indicated that the induction of NGFI-B, c-fos, and c-jun mRNA started as early as 15 minutes, reached a peak at 30 minutes, and returned to the basal level at 1 hour after the ACOI. In addition, the temporal feature of the induction of these IEG mRNA in the hippocampus was very similar to that in the cerebral cortex. Examination of brain regions at 30 minutes after the ACOI revealed a significant induction of NGFI-B mRNA in the cerebellum, thalamus-hypothalamus, brainstem. as well as in the cortex and hippocampus, but not in the striatum or olfactory bulb. Furthermore, the neuroanatomical distribution of c-fos mRNA at 30 minutes after the ACOI was very similar to that of the NGFI-B mRNA. The widespread distribution of these IEG in the brain, especially in the cerebellum and brainstem, indicates that the major cause for the triggering of IEG expression in the brain by the ACOI might be a diffuse hypoxia. These findings show for the first time the temporal and spatial expression of IEG in the brain after ACOI.
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PMID:NGFI-B, c-fos, and c-jun mRNA expression in mouse brain after acute carbon monoxide intoxication. 927 Apr 94

Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. It is characterized by a decrease of reactive oxygen intermediates and a change of the intracellular redox level. In tumors hypoxia is regarded as a trigger for enhanced growth and metastasis. Here we report that in HeLa cells, hypoxic conditions induce the transcriptional activation of c-fos transcription via the serum response element. Mutations in the binding site for the ternary complex factor Elk-1 and the serum response factor abolished this induction, indicating that a ternary complex at the serum response element is necessary for the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was covalently modified by phosphorylation in response to hypoxia. Furthermore this hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase 1. An in vitro kinase assay with Elk-1 as substrate showed that MAPK is activated under hypoxia. The activation of MAPK corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a decrease of the intracellular reactive oxygen intermediate level by hypoxia induces c-fos via the MAPK pathway. These results suggest that the intracellular redox levels may be directly coupled to tumor growth, invasion, and metastasis via Elk-1-dependent induction of c-Fos controlled genes.
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PMID:Hypoxia induces c-fos transcription via a mitogen-activated protein kinase-dependent pathway. 928 59

The effect of dexmedetomidine, a selective alpha2-adrenoreceptor agonist and neuroprotective agent on the expression of immediate early genes and heat shock protein hsp70, was studied using quantitative in situ hybridization in a global ischemia model. At the dose previously shown to be neuroprotective dexmedetomidine inhibited the expression of c-fos and hsp70 mRNA, did not affect jun-B mRNA, and enhanced the induction of NGFI-A mRNA in the postischemic gerbil hippocampus. The reduced gene expression of c-fos and hsp70 was detected in the CA1 pyramidal cells which are prone to ischemic degeneration, whereas the increased gene expression of NGFI-A was measured from the CA3 and dentate gyrus, areas relatively resistant to ischemia. These alterations in early gene expression possibly reflect the mechanisms mediating the neuroprotective effects of alpha2-adrenoreceptor agonists.
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PMID:Alpha2-adrenoreceptor agonist, dexmedetomidine, alters acute gene expression after global ischemia in gerbils. 930 90

The effects of nonselective (theophylline), A1-(DPCPX) or A2A-selective (SCH 58261) adenosine receptor antagonists administered before or after neonatal hypoxia-ischemia (HI) were studied on the extent of brain injury in 7-day-old rats evaluated after 14 days. A possible effect of theophylline (20 mg/kg) on expression of immediate early genes was studied with in situ hybridization. Theophylline (20, 30 or 60 mg/kg) given prior to HI reduced brain damage by 48% (P < 0.001), 36% (P < 0.01) and 34% (P < 0.05), respectively, compared to control rats. This effect was not explained by changes in temperature, cerebral blood flow, blood gas/acid base status or blood glucose during the insult. Theophylline enhanced the upregulation of c-fos and NFGI-A during reperfusion but did not prevent the decrease in adenosine A1 receptor mRNA. Posttreatment with SCH 58261 (0.2 or 2 mg/kg) reduced brain damage by 19% (P < 0.05) and 14% (NS), respectively, compared to control rats which was unrelated to the core temperature. DPCPX (2 or 10 mg/kg) had no effect on the development of brain injury. In conclusion, nonselective and A2A adenosine receptor antagonists reduced brain injury in a model of HI in immature animals.
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PMID:Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists. 936 88

Mice lacking the epidermal growth factor receptor (EGFR) exhibit strain-dependent phenotypes ranging from placental to postnatal skin, lung and brain defects. After birth, all mutant mice develop a progressive neurodegeneration in the frontal cortex, olfactory bulb and thalamus, characterized by massive apoptosis and upregulation of c-fos. These defects occur in a strain-independent manner, since neither rescue of the placental phenotype by aggregation of diploid 129/Sv EGFR mutant and tetraploid wild-type embryos, nor promotion of lung maturation by transplacental dexamethasone administration alters the course of neurodegeneration. VEGF is not induced during the degenerative process, excluding hypoxia and ischemia as causes of cell death. A migratory disorder is detected in the hippocampus with nests of ectopic neurons, which are also apoptotic. Cerebral cortices from EGFR mutants contain lower numbers of GFAP positive astrocytes, which display reduced proliferation in vitro. Since EGFR is expressed in the affected cell-types, these results define a specific function for EGFR in the proliferation and/or differentiation of astrocytes and in the survival of postmitotic neurons.
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PMID:A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor. 945 Sep 97

Kidney dysfunction after ischemia can be improved by either limiting the initial injury or by enhancing the subsequent proliferative repair process. Adenosine triphosphate (ATP) favorably affects kidney function when it is given shortly after ischemia. We tested whether ATP promotes the proliferative repair response. Rats were subjected to occlusion of the left renal artery for 40 minutes and received an infusion of ATP, 12.5 micromol intravenously over 30 minutes, beginning at reperfusion. Control animals received saline solution or the hydroxyl radical scavenger dimethylthiourea (DMTU). Despite comparable functional protection by DMTU and ATP, only ATP specifically increased DNA synthesis (renal incorporation of tritiated thymidine) to an extent greater than that produced by ischemia alone. In other animals, ribonucleic acid was extracted from kidneys for Northern analysis. Expression of the proto-oncogenes c-fos and c-jun was enhanced in ATP-treated animals as compared with controls. Expression of a histone protein gene (H2b) and thymidine kinase was increased by ischemia but was not additionally affected by ATP. In vitro studies of primary cultures of renal proximal tubule epithelial cells confirmed the ability of ATP to stimulate cellular proliferation as a consequence of stimulation of purinergic P2 receptors, possibly of the P2x subclass. In summary, ATP given after ischemia increased new DNA synthesis and augmented expression of genes critical to cellular proliferation. These beneficial effects were not merely a consequence of limiting initial cellular damage, and they suggest a novel mechanism of action for ATP and other purinergic receptor agonists in renal ischemia.
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PMID:Purinergic receptors mediate cell proliferation and enhanced recovery from renal ischemia by adenosine triphosphate. 948 2


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