Comprehensive gene expression analysis of cerebral cortices from mature rats after neonatal hypoxic-ischemic brain injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE37777 | GEO | 2012/06/28
SECONDARY ACCESSION(S): PRJNA163259
REPOSITORIES: GEO
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Project description:Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8% oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere. Seven-day-old Wistar rats were assigned to two groups: the control group and the Rice group (four pups in each group). HI brain insult was not induced in the control group rats. The Rice group rats were subjected to a modified LevineM-bM-^@M-^Ys procedure to induce HI brain injury. The Rice group rats were anesthetized with ether, and the left carotid artery was sectioned between double ligatures with 4-0 surgical silk. The rats were allowed to recover for 1M-bM-^@M-^S2 h and then exposed to 1 h of hypoxia in a plastic chamber that was perfused with a mixture of humidified 8% oxygen balanced with nitrogen. The temperature inside the chamber was maintained at 33 M-BM-0C, the usual temperature generated when pups huddle with the mother. The cerebral cortexes contralateral to the HI brain insult and those of the same side of the control animals were used for the experiment.
2012-06-27 | E-GEOD-37777 | biostudies-arrayexpress
Project description:Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage, and is a common cause of neurological handicaps in adulthood. The modified Levine method (Rice model) has been widely used as an animal model of this condition, which can be rescued by the administration of an antioxidant such as 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186). In the present study, by using the Rice model, we performed comprehensive gene expression and gene network analyses of neonatal HI brain insult with and without MCI-186 administration via a DNA microarray to help elucidate the molecular events responsible for the selective vulnerability of neurons to an HI insult and the underlying mechanisms of the effect of MCI-186 on the pathophysiological events. A large difference in gene expression was observed between the Rice model and the control. By performing a clustering analysis of the gene expression pattern after the HI brain insult, we found the following 3 clusters: (i) a cluster of strongly upregulated genes mainly consisting of genes related to immune responses; (ii) a cluster of mildly upregulated genes mainly consisting of genes related to cellular movement, growth and proliferation, and cell death; and (iii) a cluster of downregulated genes mainly consisting of genes related to neuronal activity. The effect of MCI-186 administration on gene expression was much less than and contrary to that of the HI brain insult. The genes upregulated and downregulated on MCI-186 administration were closely related to neuronal activity and immune responses, respectively, thereby reflecting the protective effect of MCI-186 on an HI brain insult.
2010-03-05 | GSE18356 | GEO
Project description:The aim of this study was to identify the transcriptomic response 6 hours after the MRT irradiation, in normal brain tissue (11 samples) and in glioma tissue (11 samples), in rat. The orthotopic tumor-bearing rats were either treated with MRT radiation (six MRT-tumors), or untreated (five No irradiated tumors). The contralateral half hemisphere without tumor received the MRT treatment for six rats (6 MRT-Contralateral samples) and no irradiation for five rats (5 Untreated contralateral samples). Six hours after treatment, the tumors and their controlateral regions were resected and analysed for transcriptomic response.
2015-09-01 | E-GEOD-50478 | biostudies-arrayexpress
Project description:To evaluate the change of gene expression at cerebral infarction by the treatment of IV-human umblical cord derived mesenchymal stem cell. RNA was isolated from the ipsilateral hemisphere to MCAo in rats. At 72 h post-MCAo, the ipsilateral hemisphere subjected to MCAo was used for mRNA microarray. RNA was isolated from the ipsilateral hemisphere to MCAo in rats without MCAo (control group, n=5), rats treated with 1x106 IV-hUMSC (hUMSC group, n=6) and saline (saline group, n=5) at 24h post-MCAo.
2017-03-01 | GSE78731 | GEO
Project description:We have performed both proteomic and transcriptomic analyses of the brains of one-year old Polg mutator mice. As part of this analysis, we generated RNA-Seq data from RNA isolated from one cerebral hemisphere of these mice. mRNA levels and protein abundance levels were compared in this study. 11 samples of RNA isolated from mouse cerebral hemisphere. 7 Polg D257A/D257A, 1 Polg D257A/WT, and 3 Polg WT/WT. The samples were collected from one-year old male mice.
2015-02-18 | E-GEOD-55188 | biostudies-arrayexpress
Project description:Hypoxic-ischemic (HI) injury in the developing brain is a common cause of disability in children, and there are no effective treatments at this time. Erythropoietin (EPO) has recently gained interest as a neuroprotective drug, and EPO and its receptor are expressed within the central nervous system. We have recently shown that pretreatment with EPO markedly reduced brain injury caused by unilateral hypoxic-ischemic insult in 7 day old mice. EPO did not reduce early signs of neuronal injury at 6 hours, but significantly protected the neonatal brain when assessed 24 hours and 7 days after HI. The mechanism of this delayed protection is unclear, but is thought to involve transcription of neuroprotective genes, possibly subsequent to activation of NFkB. By comparing gene expression in EPO- and vehicle- (VEH) treated mice after HI, we should gain insight into the mechanisms underlying the neuroprotective effects of EPO and may identify additional targets for therapeutic interventions. We will compare gene expression patterns in 7-day old mouse forebrain after 1) VEH pretreatment plus sham surgery, 2) VEH pretreatment plus HI, and 3) EPO pretreatment plus HI. We will thus identify genes induced by HI in the developing brain and characterize changes in gene expression caused by EPO pretreatment. We will use the model of neonatal hypoxic-ischemic injury and EPO treatment parameters that were used in our prior studies demonstrating neuroprotection. Based on the time-course of neuroprotection defined in our prior study and the pharmacokinetic profile of EPO, we will examine gene expression 18 hours after HI. We hypothesize that changes in gene expression after EPO pretreatment underlie the neuroprotective effects of this cytokine after neonatal hypoxic ischemic injury. We will examine gene expression in 3 groups: 1) 1) VEH pretreatment + sham surgery, 2) VEH pretreatment + HI, and 3) EPO pretreatment + HI. EPO (5U/g, i.p.) or VEH was injected in 7 day old mice, drawn from 4 litters, with 3 to 4 pups per treatment group in each litter. One hour later, the right common carotid artery was ligated under isoflurane anesthesia, animals were allowed to recover for 90 min and were then placed in hypoxic chambers (10% oxygen, balance nitrogen) for 50 min. The animals subjected to sham surgery received isoflurane anesthesia for a comparable period, incision and dissection to visualize the common carotid artery, but no ligation and no hypoxia. Eighteen hrs later, animals were anesthetized with isoflurane and the right hemisphere was rapidly dissected and placed in RNA Later (Qiagen) at 4C. Total RNA was isolated using an RNeasy lipid tissue mini kit (QIAzol lysis and RNeasy purification, Qiagen). RNA concentrations were determined spectrophotometrically and an aliquot of each sample was examined by gel electrophoresis to screen for degradation. Samples were stored at -80C. After quality control screening, we selected 5 male and 5 female samples per treatment group (extra samples were reserved). We plan to pool 1 male and 1 female for each microarray sample and we plan to run 5 microarrays from each treatment group, for a total of 15 microarrays. We would like to have Agilent Bioanalyzer quality control assays on the individual samples carried out by the consortium before pooling. We will send 10 micrograms of each sample for Agilent QC and subsequent pooling of equimolar amounts. We would like to use Affymetrix mouse gene chips (please advise which specific chips are available; are you using the GeneChip Mouse Expression array 430A or the GeneChip Mouse Genome 430 2.0 Array?).
2007-11-06 | E-GEOD-1999 | biostudies-arrayexpress
Project description:Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.
2022-09-27 | GSE205142 | GEO
Project description:Comprehensive gene expression analysis of cerebral cortices from mature rats after neonatal hypoxic-ischemic brain injury
| PRJNA163259 | ENA
Project description:Hypoxia-ischemia (HI) brain damage is one of the most common causes of neonatal brain injuries, amidst other conditions such as intrauterine infection and perinatal cerebral hemorrhage (Bracci et al., 2006). HI, occurring during the perinatal period, severely affects brain integrity resulting in detrimental long-term neurological morbidity in terms of motor, intellectual, educational and neuropsychological performance deficits (e.g. cerebral palsy, mental retardation, learning disability and epilepsy), and even neonatal mortality (Cowan et al., 2003; Ferriero, 2004; van Handel et al., 2007; Shalak and Perlman, 2004). Current therapeutic interventions fail to provide substantial reversal of HI brain injuries and improvement in overall cognitive function. Recent clinical studies demonstrated that post-HI hypothermia provide moderate neuroprotection but fail to show any significant reduction in neonatal morbidity and mortality (Shankaran et al., 2005). We would like to investigate the transcriptional effects of HI on neonatal brain, and if hypoxic pre-conditioning is beneficial to the reduction of brain damage. Microarray analysis was performed on the cortex of neonatal brains using Illumina mouse Ref8 V2 genechips. The right common carotid artery was exposed through a ventral midline neck incision and permanently occluded by electrocoagulation, The wound was sutured and mouse pups were returned to their mother for 1.5M-bM-^@M-^S2 h. Sham control and pre-conditioned mice (n = 4) underwent the identical procedure, without carotid artery occlusion. Pups were then placed in an 8% O2/92% N2 humidified chamber at 37M-BM-0C for 1 h with tissue extraction taking place 3h, 8h and 24h thereafter (n=4 respectively). Sham controls were included in this study too (n=4 respectively).
2013-12-31 | E-GEOD-23317 | biostudies-arrayexpress
Project description:Hypoxia-ischemia (HI) brain damage is one of the most common causes of neonatal brain injuries, amidst other conditions such as intrauterine infection and perinatal cerebral hemorrhage (Bracci et al., 2006). HI, occurring during the perinatal period, severely affects brain integrity resulting in detrimental long-term neurological morbidity in terms of motor, intellectual, educational and neuropsychological performance deficits (e.g. cerebral palsy, mental retardation, learning disability and epilepsy), and even neonatal mortality (Cowan et al., 2003; Ferriero, 2004; van Handel et al., 2007; Shalak and Perlman, 2004). Current therapeutic interventions fail to provide substantial reversal of HI brain injuries and improvement in overall cognitive function. Recent clinical studies demonstrated that post-HI hypothermia provide moderate neuroprotection but fail to show any significant reduction in neonatal morbidity and mortality (Shankaran et al., 2005). We would like to investigate the transcriptional effects of HI on neonatal brain, and if hypoxic pre-conditioning is beneficial to the reduction of brain damage. Microarray analysis was performed on the striatum of neonatal brains using Illumina mouse Ref8 V2 genechips. The right common carotid artery was exposed through a ventral midline neck incision and permanently occluded by electrocoagulation, The wound was sutured and mouse pups were returned to their mother for 1.5M-bM-^@M-^S2 h. Sham control and pre-conditioned mice (n = 4) underwent the identical procedure, without carotid artery occlusion. Pups were then placed in an 8% O2/92% N2 humidified chamber at 37M-BM-0C for 1 h with tissue extraction taking place 3h, 8h and 24h thereafter (n=4 respectively). Sham controls were included in this study too (n=4 respectively).
2013-12-31 | E-GEOD-23319 | biostudies-arrayexpress