Global transcriptomic profiling of hypoxic ischemia in an in vivo neonatal mouse model
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Minghui Jessica Chen
PROVIDER: E-GEOD-23333 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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).
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Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 7,865 phosphopeptides,179 phosphorylation sites of 129 proteins were upregulated and 843 phosphorylation sites of 494 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation.
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Project description:We obtained the profiles of neuronal proteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 5,059 proteins. We identified 142 differentially expressed proteins (t-test, p-value<0.05) after IR compared to sham groups. The results showed that 92 proteins were upregulated, and 50 proteins were downregulated after IR compared to sham groups. Gene ontology (GO) enrichment analysis of differentially expressed proteins between sham and IR groups. The results showed that the biological process of most of upregulated genes linked with immune inflammatory related responses were increased. And KEGG pathway analysis for upregulated genes showed that multiple immune inflammatory response pathways also increased significantly, such as TNF-signaling, NF-κB signaling and cytokine-cytokine receptor interaction, as well as NOD-like receptor signaling, and toll-like receptor signaling.
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Project description:Complete global brain ischemia (CGBI) and reperfusion occur following resuscitation from cardiac arrest. Different brain neurons are selectively vulnerable to CGBI: pyramidal neurons of hippocampal CA3 survive 10 min CGBI but those of CA1 die at 3 days following 10 min CGBI. CA3 neurons are expected to have more robust stress responses and repair responses than CA1 neurons. We used microarrays to compared total and polysome-bound mRNAs in CA1 and CA3 at 8 hr reperfusion after 10 min CGBI in Long Evans male rats to ascertain differences in total vs polysome-bound gene expression. Male Long Evans rats were subjected to (1) sham operation (non-ischemic control, NIC) or normothermic CGBI of 10 min followed by 8 hr reperfusion (8R). Hippocampal CA1 and CA3 were dissected. n = 5 CA1 or CA3 were pooled to give a single replicate and there were 3 or 4 replicates per group. Post-mitochondrial supernatant (PMS) was prepared. Twenty percent of PMS was TRIzol extracted to give total RNA. The remainder was run on a 20% sucrose pad to isolate polysome pellets, which were also TRIzol extracted to give polysome RNA. Total and polysome RNA were then run on Affymetrix Rat Gene 2.0 microarrays.
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Project description:To investigate the Wuzang Wenyang Huayu Decoction Regulates Differentially Expressed Proteins in the Rat, Hippocampus after Cerebral Hypoperfusion.
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Project description:This study aims at a comprehensive understanding of the genomic program activated during early-phase of collateral vessel growth in a rat model for cerebral adaptive arteriogenesis (3-VO). While arteriogenesis constitutes a promising therapeutic concept for cerebrovascular ischemia, genomic profiles essential for therapeutic target identification were analysed solely for collateral arteries of the heart and periphery. Despite challenging anatomical conditions of the brain the 3-VO model allows identification of differentially expressed genes during adaptive cerebral arteriogenesis by selective removal of the posterior cerebral artery (PCA). Experiment Overall Design: Using an established rat model of nonischemic cerebral hypoperfusion (3-VO) (Busch, Buschmann; 2003), RNA was extracted from isolated ipsilateral PCA. Pooled RNAs from groups of intact (0h), sham and 3-VO animals 24h and 3 days after surgery, were hybridised repeatedly for an extensive genome screen of 15866 genes applying standardized Affymetrix technology. For each Array total RNA from 8 animals was processed, pooled and hybridized to a Rat230A GeneChip per group. These groups were classified as follows: intact control (N=3), 24h3VO (N=3); 24h sham (N=3), 3days3VO (N=3); and 3days sham(N=3). Hybridization, washing, antibody amplification, staining, and scanning of probe arrays were performed according to the Affymetrix Technical Manual. Probe arrays were scanned using the GeneChip System (Hewlett-Packard, Santa Cruz, CA)(Affymetrix) and raw data were processed using GCOS and normalized to a global intensity of 500.
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Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia onset by isolating mice hippocampus. Hippocampus combined from either ten sham or ten focal cerebral ischemia 2 h mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. Five percent of the pool was used for whole proteome analysis, and the remaining 95% was subjected to phosphoproteome profiling. In total, we quantified 5,174 proteins and 9,062 phosphopeptides. Interesting, 21 proteins were upregulated and 7 proteins were downregulated in hippocampus lysates of cerebral ischemia 2 h relative to sham base on fold change. S100a9, Alpha-2-HS-glycoprotein (Ahsg), Fibrinogen beta chain (Fga) and Complement Component C3(c3) are the top significantly changed, which were highly consistent with previous reports in cerebral ischemia injury. Using wolfpsort software to analysis the Subcellular Location, 57% of detected proteins were location to extracellular, 15% were cytoplasmic protein, another 11% were transport to nucleus, and the others were location to plasma membranes (10%), mitochondria (4%) and endoplasmic reticulum (3%). Moreover,184 phosphorylation sites of 135 proteins were upregulated and 689 phosphorylation sites of 420 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation. Employing wolfpsort software analysis the subcellular location, 50% of phosphorylated proteins were location to nucleus, 26% were cytoplasmic protein, another 16% were transport to plasma membranes, and the others were location to mitochondria (4%), extracellular (3%) and cytoskeleton (1%). Motif analysis showed that 85% were belongs to serine-type phosphorylation, about 14 were threonine-type phosphorylation and 1% were tyrosine-type phosphorylation.
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