Global gene regulation in permanent focal ischemia in an in vivo rat model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE25676 | GEO | 2013/12/31
SECONDARY ACCESSION(S): PRJNA133873
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-31 | E-GEOD-25676 | biostudies-arrayexpress
Project description:Focal ischemia is triggered by the sudden significant reduction of blood supply to the brain, as a result of either the rupture or occlusion by thrombus/embolism of a blood vessel in the brain. Permanent focal ischemia occurred when blood supply to a specific part of the brain is impeded without reperfusion. Despite major steps achieved in the elucidation of the patho-physiology of cerebral ischemia, the available therapeutic avenues for acute ischemic stroke remain scarce. Cell cycle re-activation has been revealed as a novel signaling pathway during permanent focal ischemia. As such, non-specific aurora kinase inhibitor ZM447439, has been injected intracranial-ventricularly30min post-ischemia induction to determine its efficacy in reduction of neuronal damage in terms of infarct volume.
2013-12-31 | GSE23651 | GEO
Project description:Focal ischemia is triggered by the sudden significant reduction of blood supply to the brain, as a result of either the rupture or occlusion by thrombus/embolism of a blood vessel in the brain. Permanent focal ischemia occurred when blood supply to a specific part of the brain is impeded without reperfusion. Despite major steps achieved in the elucidation of the patho-physiology of cerebral ischemia, the available therapeutic avenues for acute ischemic stroke remain scarce. Cell cycle re-activation has been revealed as a novel signaling pathway during permanent focal ischemia. As such, non-specific aurora kinase inhibitor ZM447439, has been injected intracranial-ventricularly30min post-ischemia induction to determine its efficacy in reduction of neuronal damage in terms of infarct volume. Microarray analysis was performed on Illumina Rat Ref12V1 beadchips. Right cortex RNA samples were collected at two time-points (8h and 24h ) respectively for all three experimental conditions: Sham (n=4), vehicle (i.e. ischemic injury with i.c.v. injection 80% DMSO; n=4) and treatment (injury plusi.c.v.injection of 30mM ZM447439 in 80% DMSO; n=4).
2013-12-31 | E-GEOD-23651 | biostudies-arrayexpress
Project description:Focal ischemia is triggered by the sudden significant reduction of blood supply to the brain, as a result of either the rupture or occlusion by thrombus/embolism of a blood vessel in the brain. Permanent focal ischemia occurred when blood supply to a specific part of the brain is impeded without reperfusion. Despite major steps achieved in the elucidation of the patho-physiology of cerebral ischemia, the available therapeutic avenues for acute ischemic stroke remain scarce. Cell cycle re-activation has been revealed as a novel signaling pathway during permanent focal ischemia. As such, non-specific aurora kinase inhibitor ZM447439, has been injected intracranial-ventricularly 30min post-ischemia induction to determine its efficacy in reduction of neuronal damage in terms of infarct volume.
2013-12-31 | GSE25556 | GEO
Project description:Focal ischemia is triggered by the sudden significant reduction of blood supply to the brain, as a result of either the rupture or occlusion by thrombus/embolism of a blood vessel in the brain. Permanent focal ischemia occurred when blood supply to a specific part of the brain is impeded without reperfusion. Despite major steps achieved in the elucidation of the patho-physiology of cerebral ischemia, the available therapeutic avenues for acute ischemic stroke remain scarce. Cell cycle re-activation has been revealed as a novel signaling pathway during permanent focal ischemia. As such, non-specific aurora kinase inhibitor ZM447439, has been injected intracranial-ventricularly 30min post-ischemia induction to determine its efficacy in reduction of neuronal damage in terms of infarct volume. miRNA microarray analysis was performed on Exiqon 5th generation - hsa, mmu & rno (Product no: 208300-A) to compliment our existing gene expression microarray data [GSE23651]. Arrays were run as dual colour (Hy3: Sample, and Hy5: Common sample reference pool). Right cortex RNA samples were collected at two time-points (8h and 24h )respectively for all three experimental conditions: Sham (n=4), vehicle (i.e. ischemic injury with i.c.v. injection 80% DMSO; n=4) and treatment (injury plus i.c.v.injection of 30mM ZM447439 in 80% DMSO; n=4). Supplementary file: Project_Summary_Report.txt The percentages listed in the top row are present-call rates, i.e. number of identified miRNAs compared to number of miRNAs on array.
2013-12-31 | E-GEOD-25556 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-31 | E-GEOD-23333 | biostudies-arrayexpress
Project description:Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not 40S or 60S ribosomal subunits, or organelle markers. The volume of brain with mRNA granule-containing neurons decreased exponentially with ischemia duration, and was zero after 8 h permanent focal cerebral ischemia or any duration of ischemia in diabetic rats. These results show that neuronal mRNA granule response has a limited range of insult intensity over which it is expressed. Identifying the limits of effective neuronal stress response to ischemia will be important for developing effective stroke therapies.
| S-EPMC3864703 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-12-31 | GSE23333 | GEO
Project description:Xueshuantong for Injection (Lyophilized) (XST), a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk.), is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx) 6-toll-like receptor (TLR) 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO) induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1? (IL-1?), IL-17, IL-23p19, tumor necrosis factor-? (TNF?), and inducible nitric oxide synthase (iNOS) in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx) 6-toll-like receptor (TLR) 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats' weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.
| S-EPMC4670871 | biostudies-literature
Project description:Ischemic postconditioning is increasingly being investigated as a therapeutic approach for cerebral ischemia. However, the majority of studies are focused on the acute protection of neurons per se. Whether and how postconditioning affects multiple cells in the recovering neurovascular unit remains to be fully elucidated. Here, we asked whether postconditioning may modulate help-me signaling between injured neurons and reactive microglia. Rats were subjected to 100 min of focal cerebral ischemia, then randomized into a control versus postconditioning group. After 3 days of reperfusion, infarct volumes were significantly reduced in animals treated with postconditioning, along with better neurologic outcomes. Immunostaining revealed that ischemic postconditioning increased expression of vascular endothelial growth factor (VEGF) in neurons within peri-infarct regions. Correspondingly, we confirmed that VEGFR2 was expressed on Iba1-positive microglia/macrophages, and confocal microscopy showed that in postconditioned rats, these cells were polarized to a ramified morphology with higher expression of M2-like markers. Treating rats with a VEGF receptor 2 kinase inhibitor negated these effects of postconditioning on microglia/macrophage polarization. In vitro, postconditoning after oxygen-glucose deprivation up-regulated VEGF release in primary neuron cultures, and adding VEGF to microglial cultures partly shifted their M2-like markers. Altogether, our findings support the idea that after postconditioning, injured neurons may release VEGF as a 'help-me' signal that promotes microglia/macrophage polarization into potentially beneficial phenotypes.
| S-EPMC6105375 | biostudies-literature