Project description:Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.7±1.8) and Dex (2.3±1.2) was reduced (P<0.05) compared to Vehicle (3.8±0.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to uninjured/untreated control (0.14±0.26) group. At 24h post-IR urine Lipocalin-2 (µg/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67±o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.7±1.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6± 1.5) compared to Vehicle (Grade 2.9±1.1) group. Inflammatory cytokines IL1β and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury. We had three experimental groups. Group A, VPA treatment; Group B, Dexamethasone treatment; and Group C, No treatment (vehicle saline control). Treatments were administered prior to the induction of left renal ischemia. Animals underwent 45 minutes of left renal ischemia, followed by reperfusion, and right nephrectomy as described above. Following reperfusion, animals were sacrificed at 3, 24 or 120 hours (n=8/group). In the 3 hour group, rats were maintained under anesthesia after surgery until sacrifice. In the 24 and 120 hour groups, the rats were recovered and returned to the cages for normal housing. Analgesic buprenorphine (0.05mg/kg) was administered every 12 h for three days post-operatively. After animal sacrifice, urine, blood, and kidney were collected for kidney functional biomarker assays, histology and / or molecular analyses. Urine was obtained via cystocentesis and blood was obtained via the left renal vein. Tissue and urine samples collected from normal (naïve) animals (n=5) were used for baseline measurements. A subset of 46 animals (n = 4-5 per group) were selected for microarray analysis.

Project description:Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.7±1.8) and Dex (2.3±1.2) was reduced (P<0.05) compared to Vehicle (3.8±0.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to uninjured/untreated control (0.14±0.26) group. At 24h post-IR urine Lipocalin-2 (µg/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67±o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.7±1.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6± 1.5) compared to Vehicle (Grade 2.9±1.1) group. Inflammatory cytokines IL1β and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury.

Project description:We are searching for common gene expression alteration in the hippocampus of animal models of learning disabilities and in post-mortem human tissues derived from patients with cognitive deficits. Our study has three phases. In phase I, we want to investigate the changes in gene expression in a transgenic mouse line that shows impairments in hippocampal-dependent learning. These animals are overexpressing the RNA-binding protein HuD in the forebrain under the control of the alpha CAMKinII promoter. For phase II, we plan to characterize the hippocampus of another animal model of learning disabilities: fetal alcohol exposed (FAE) rats. Last, for phase III, we would like to examine gene expression changes in the hippocampus and other tissues from patients with schizophrenia. To test our hypothesis, in phase 2 of our project, we propose to compare the pattern of gene expression in our mouse model with that in the hippocampus of rats prenatally exposed to alcohol (FAE model). Our hypothesis is that learning disabilities have common neural substrates regardless of the origin of the disability being genetic, environmental of a combination of these two. To test this hypothesis, we plan to examine the pattern of gene expression in the hippocampus of animals and humans with cognitive deficits and use bioinformatics tools to identify common changes in gene expression in three of such conditions: a genetic model (HuD transgenic mice), an environmental model (FAE rats) and a model for combined environmental and genetic effects (patients with schizophrenia). All the animals are adult male Sprague-Dawley rats (age 90-100 days). Animals were divided in three diet groups and three experimental treatment conditions (9 conditions altogether). Three groups of pregnant rat dams were placed on different diet regimens: a liquid diet containing 5% alcohol (A) groups, a control group fed an isocaloric liquid diet without alcohol (B) and a group of rats fed lab chow ad libitum (C). Offspring from each of these groups were allowed to grow until adulthood and placed into each of three training groups: a contextual fear conditioned group (1), a non-learning stress control group (2) and a naive/unhandled group (3). Hippocampi were dissected and used to isolate total RNA from each rat diet and training condition. Initially, we will submit 18 samples as follows: 10 samples from training group 1 and 8 samples from training group 3 (training group 2 will be analyzed at a later date). The diet assignment for the 18 samples is: 8 samples from group A, 6 samples of group B and 4 samples of group C. Please note that I was able to enter only the first 8 samples, as the sample list does not hold 18 samples altogether. Keywords: dose response

			Action	DRS
	SRR33778668_1.fastq.gz	Fastqsanger.gz
	SRR33778668_2.fastq.gz	Fastqsanger.gz
	SRR33778669_1.fastq.gz	Fastqsanger.gz
	SRR33778669_2.fastq.gz	Fastqsanger.gz
	SRR33778670_1.fastq.gz	Fastqsanger.gz

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Rattus norvegicus

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