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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brief periods of cerebral ischemia result in prolonged inhibition of protein synthesis. In CA1 sector of hippocampus inhibition is irreversible, leading to delayed death of pyramidal neurons. In order to study the possible role of gene transcription in this process, expression of four individual RNAs was investigated in the gerbil brain after 5 min of global cerebral ischemia by in situ hybridization with the following nucleic acid probes: plasmid pMr100 (ribosomal RNA sequences), plasma pAG82 (cytochrome c oxidase sequences), plasmid p629 (amyloid A4 precursor protein of Alzheimer's disease, pre-A4 protein), and plasmid pHF beta A-1 (beta-actin sequences). Cytochrome c oxidase mRNA and ribosomal RNA did not show any changes in expression up to 48 hr after ischemia. After longer recirculation times they gradually declined in the CA1 sector of hippocampus in parallel with the morphological manifestation of delayed neuronal death. The pre-A4 mRNA transiently decreased after 8 hr of recirculation of the CA1 sector but then recovered before it finally disappeared in parallel with delayed neuronal death. The beta-actin mRNA transiently appeared to increase after 8 hr of recirculation in the stratum radiatum of hippocampus but then also declined and disappeared when CA1 neurons began to disintegrate. The possible significance of these changes in the pathogenesis of ischemic neuronal damage is discussed.
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PMID:Determination of RNA content in postischemic gerbil brain by in situ hybridization. 248 Dec 24

Loss of intracellular calcium homeostasis has been regarded an important factor underlying neuron cell death after cerebral ischemic insult. In the brain, a major mechanism for regulation of intracellular calcium is through the signal transduction pathway involving hydrolysis of poly-phosphoinositides and release of the second messenger, inositol 1,4,5-trisphosphate (IP3). IP3 mobilizes calcium by interacting with an intracellular receptor. Upon its release after agonist stimulation, this second messenger is catabolized by a 3-kinase and a 5-phosphatase. In this study, in situ hybridization was carried out to examine the mRNA expression of IP3, receptor (IP3R) and IP3 3-kinase (IP3K) in rat brain cortex after transient focal cerebral ischemia induced by temporary occlusion of the middle cerebral artery (MCA) and the common carotid arteries (CCAs). Results indicate a large decrease (52%) in IP3R mRNA levels in the ischemic cortex as compared to that in the contralateral side at 4 h after a 45 min ischemic insult. By 16 h, practically no IP3R mRNA could be detected in the ischemic cortex. On the other hand, IP3K mRNA levels remained unaltered until 16 h after reperfusion, during which time, expression in the infarct core decreased but that surrounding the core area increased instead. Hybridization of adjacent brain sections with probes for neuron specific enolase (NSE) and beta-actin indicated also a time-dependent decrease in mRNA levels after ischemia, but these changes were less dramatic as compared to IP3R. At 16 and 24 h after reperfusion, there was an increase in beta-actin mRNA in cortical areas outside the MCA cortex, suggesting of reactive gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ hybridization of mRNA expression for IP3 receptor and IP3-3-kinase in rat brain after transient focal cerebral ischemia. 750 Aug 36

Regional changes in the mRNA accumulations for cytoskeletal proteins alpha-tubulin and beta-actin were examined by in situ hybridization and Northern blot analysis in spontaneously hypertensive rat brains at chronic stages after 3 hours of transient ischemia. alpha-Tubulin mRNA accumulations showed no significant change at 2 weeks after transient ischemia except for a significant decrease in the frontal cortex (9.7%, p < 0.01) coinciding with ischemia induced histological changes. beta-Actin mRNA level was significantly increased in the parietal cortex (8.5%), septum (10.0%), amygdala (11.0%), CA4 area (5.8%) and the dentate gyrus (7.5%) of the hippocampus at 2 weeks after recirculation compared with a sham-operated control group (p < 0.01). The ischemic areas of hippocampal and frontocortical lesions receive afferent neurons from those regions where beta-actin mRNA was increased, suggesting that ischemia-induced increases in beta-actin mRNA may reflect actin synthesis in these neurons to compensate for lost synaptic connections. Two cytoskeletal mRNA concentrations reacted differently to cerebral ischemia, and did not parallel histological signs of ischemia either temporally or spatially.
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PMID:Regional changes in alpha-tubulin and beta-actin mRNA accumulations after transient ischemia in spontaneously hypertensive rat brains. 788 65

Global cerebral ischemia induced to Mongolian gerbils by ligation of common carotid arteries (CCAs) is known to result in injury to the hippocampal CA1 region. In this study, we examined whether neuronal injury can be depicted by measuring levels of mRNA encoding inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), neuron specific enolase (NSE) and beta-actin and whether these measurements can be use to assess ischemic tolerance. Gerbils were subjected either to cerebral ischemia induced by ligation of both CCAs for 5 min, or to an ischemic tolerance paradigm in which a 2 min ischemic preconditioning was performed 24 hr prior to the 5 min ischemia. At 48 hr after the 5 min ischemic insult, significant decreases in mRNA levels for IP3R1 (26%), NSE (38%) and beta-actin (50%) could be observed in the hippocampal CA1 region. Although levels of mRNA in the preconditioning group were decreased as compared to the sham control, the levels were significantly higher than those in the ischemic group. These results indicate the feasibility of using mRNA measurement as a parameter to assess cerebral ischemic damage. In addition, based on the differences in the decline in mRNA levels between the ischemia group and the preconditioned ischemia group, it can be concluded that this ischemic tolerance paradigm could offer partial protection (around 45%) against the injury due to the 5 min cerebral ischemic insult.
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PMID:Effects of ischemic tolerance on mRNA levels of IP3R1, beta-actin, and neuron-specific enolase in hippocampal CA1 area of the gerbil brain. 956 89

We examined the uptake and distribution of an antisense phosphorothioated oligodeoxynucleotide (s-ODN) to c-fos, rncfosr115, infused into the left cerebral ventricle of male Long-Evans rats and the effect of this s-ODN on subsequent Fos, NGF, neurotrophin-3 (NT-3), and actin expression. To establish the uptake and turnover of s-ODN in the brain, we studied the copurification of the immunoreactivity of biotin with biotinylated s-ODN that was recovered from different regions of the brain. A time-dependent diffusion and the localization of s-ODN were further demonstrated by labeling the 3'-OH terminus of s-ODN in situ with digoxigenin-dUTP using terminal transferase and detection using anti-digoxigenin IgG-FITC. Cellular uptake of the s-ODN was evident in both the hippocampal and cortical regions, consistent with a gradient originating at the ventricular surface. Degradation of the s-ODN was observed beginning 48 hr after delivery. The effectiveness of c-fos antisense s-ODN was demonstrated by its suppression of postischemic Fos expression, which was accompanied by an inhibition of ischemia-induced NGF mRNA expression in the dentate gyrus. Infusion of saline, the sense s-ODN, or a mismatch antisense s-ODN did not suppress Fos expression. That this effect of c-fos antisense s-ODN was specific to NGF was demonstrated by its lack of effect on the postischemic expression of the NT-3 and beta-actin genes. Our results demonstrate that c-fos antisense s-ODN blocks selected downstream events and support the contention that postischemic Fos regulates the subsequent expression of the NGF gene and that Fos expression may have a functional component in neuroregeneration after focal cerebral ischemia-reperfusion.
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PMID:Suppression of postischemic hippocampal nerve growth factor expression by a c-fos antisense oligodeoxynucleotide. 995 11

Previous studies have demonstrated that cerebral ischemia stimulated the increased abundance of immunoreactive PGHS-2, but not PGHS-1, in brain tissue homogenates in late-gestation fetal sheep. The goal of the present study was to detect PGHS-1 and PGHS-2 mRNA in specific fetal brain regions, and to semi-quantitatively detect changes in the abundance of the respective mRNA's in response to cerebral hypoperfusion. Fetal brain tissues were collected from control fetuses and from fetuses 30 min and 2 h after cerebral hypoperfusion (produced by brachiocephalic occlusion). Messenger RNA was studied by RT-PCR, and expressed semiquantitatively as a ratio of PGHS-1 or PGHS-2 mRNA abundance to beta-actin mRNA abundance. PGHS-2 mRNA was only detected in the fetal hippocampus, hypothalamus, and brain stem and it was induced by cerebral hypoperfusion. In contrast, PGHS-1 mRNA was detected in all fetal brain tissues but was not induced. We conclude that cerebral hypoperfusion induced PGHS-2 gene expression in hippocampus, hypothalamus, and brainstem, and we speculate that the increased abundance of the enzyme is likely to be important for control of reflex responses to hypotension in the fetus.
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PMID:Induction of PGHS-2 mRNA in response to cerebral hypoperfusion in late-gestation fetal sheep. 1093 10

Expression levels of mRNA are commonly measured as a ratio of test to reference gene. The assumption is that reference genes such as beta-actin or cyclophilin are unaffected by treatment and act as steady-state controls. TaqMan real-time RT-PCR was used to test these assumptions in a rat model of cerebral ischaemia (tMCAO). Following measurement of 24 genes, we show that reference genes in this animal model fail the criteria for steady-state controls. Neuronal loss, glial proliferation and an influx of leukocytes into the lesioned brain result in major disturbance to cell populations. The mRNA for reference genes, as for test genes, reflects these changes. Specific mRNA levels vary according to the choice of reference gene to which they are normalised. In the process of resolving reference gene issues, mRNA increases were discovered for leukaemia inhibitory factor, nestin and galanin in rat brain hemispheres affected by ischaemia. Results are reported for a further 21 genes and mathematical and statistical methods are described that allow in this study fraction-fold changes in mRNA to be detected.
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PMID:The quantification of gene expression in an animal model of brain ischaemia using TaqMan real-time RT-PCR. 1239 70

beta-Actin is often used as a housekeeping gene when performing reverse transcription-polymerase chain reaction (RT-PCR) analysis for cerebral ischemia models. In the present study, we tested two different control genes used for RT-PCR experiments, beta-actin and porphobilinogen deaminase (PBG-D), in a rat model of focal cerebral ischemia under normo- or hyperglycemic conditions. A three-vessel occlusion model with permanent middle cerebral artery occlusion was used in the rat. beta-Actin mRNA expression was decreased in hyperglycemic ischemic rats compared to normoglycemic ischemic animals 3 h post-ischemia. beta-Actin protein content was unchanged. As for PBG-D, its mRNA expression remained constant throughout the groups. Our data thus show that, following focal cerebral ischemia in hyperglycemic conditions, beta-actin is an unsuitable housekeeping gene whereas PBG-D is more appropriate. This study clearly demonstrates the importance of selecting a stable housekeeping gene when performing RT-PCR experiments.
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PMID:Decreased beta-actin mRNA expression in hyperglycemic focal cerebral ischemia in the rat. 1500 87

From conventional relative gene expression analyses (Northern blotting, in situ hybridization, and RT-PCR), it has been reported that the expression of control genes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, used as references may be affected by ischemia. Therefore, we extended searching and evaluation at the mRNA level of transcripts whose expression levels were not changed by cerebral ischemia, using a high-density oligonucleotide array and statistical analysis in a rat global cerebral ischemia and reperfusion model. We added a hyperthermic factor and localization factor to ischemia and identified transcripts with a stable expression level under conditions even more disadvantageous than ischemia only. Screening of more than 8,000 transcripts with the Rat Genome U34A array yielded 28 transcripts, which we listed and classified according to their expression level. Widely used control genes, GAPDH and beta-actin, were not included, although cyclophilin A was included. In addition, we conducted a functional classification based on gene ontology. Under the functional classification of the 28 transcripts, many genes tended to be associated with metabolism. In conclusion, use of several transcripts is recommended, such as those we identified, as references in the analysis of gene expression in pathological models of ischemia.
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PMID:Screening for control genes in rat global cerebral ischemia using high-density oligonucleotide array. 1511 23

We investigated the effects of PACAP treatment, and endogenous PACAP deficiency, on infarct volume, neurological function, and the cerebrocortical transcriptional response in a mouse model of stroke, middle cerebral artery occlusion (MCAO). PACAP-38 administered i.v. or i.c.v. 1 h after MCAO significantly reduced infarct volume, and ameliorated functional motor deficits measured 24 h later in wild-type mice. Infarct volumes and neurological deficits (walking faults) were both greater in PACAP-deficient than in wild-type mice, but treatment with PACAP reduced lesion volume and neurological deficits in PACAP-deficient mice to the same level of improvement as in wild-type mice. A 35,546-clone mouse cDNA microarray was used to investigate cortical transcriptional changes associated with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP treatment after MCAO in wild-type mice. 229 known (named) transcripts were increased (228) or decreased (1) in abundance at least 50% following cerebral ischemia in wild-type mice. 49 transcripts were significantly up-regulated only at 1 h post-MCAO (acute response transcripts), 142 were up-regulated only at 24 h post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at both times (sustained response transcripts). More than half of these are transcripts not previously reported to be altered in ischemia. A larger percentage of genes up-regulated at 24 hr than at 1 hr required endogenous PACAP, suggesting a more prominent role for PACAP in later response to injury than in the initial response. This is consistent with a neuroprotective role for PACAP in late response to injury, i.e., even when administered 1 hr or more after MCAO. Putative injury effector transcripts regulated by PACAP include beta-actin, midline 2, and metallothionein 1. Potential neuroprotective transcripts include several demonstrated to be PACAP-regulated in other contexts. Prominent among these were transcripts encoding the PACAP-regulated gene Ier3, and the neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.
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PMID:Neuroprotection by endogenous and exogenous PACAP following stroke. 1702 94


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