Project description:Large clinical studies have shown that AT1 receptor blockers (ARBs) reduce the incidence of stroke in patients at risk. However, there is controversy about the underlying pathomechanisms. To get a closer insight into the effects of ARBs in stroke on molecular level, gene expression pattern was compared in the ischemic brain areas of Candesartan pre-treated (0,2 mg/kg bwt., 5 days, s.c.) versus vehicle treated, normotensive, adult rats after middle carotid artery occlusion (MCAO). Candesartan significantly improved neurological outcome (as estimated by Garcia-scale) 24 h and 48 h after stroke and reduced infarct volume by about 40% compared to vehicle. Keywords: disease state analysis
Project description:Large clinical studies have shown that AT1 receptor blockers (ARBs) reduce the incidence of stroke in patients at risk. However, there is controversy about the underlying pathomechanisms. To get a closer insight into the effects of ARBs in stroke on molecular level, gene expression pattern was compared in the ischemic brain areas of Candesartan pre-treated (0,2 mg/kg bwt., 5 days, s.c.) versus vehicle treated, normotensive, adult rats after middle carotid artery occlusion (MCAO). Candesartan significantly improved neurological outcome (as estimated by Garcia-scale) 24 h and 48 h after stroke and reduced infarct volume by about 40% compared to vehicle. Experiment Overall Design: For gene expression profiling, RNA of two animals per group was pooled and forwarded to preparation of the labeled targets for the micro array experiment. For each biological condition two independent pools were hybridised onto Affymetrix RAE 230A arrays.
Project description:Severe cerebral ischemia caused by events such as ischemic stroke or cardiac arrest is a relatively common and life-threating condition. Those who survive frequently suffer from significant cerebral dysfunction, often with poor outcome. To date the treatment options are limited. Concomitant hyperglycemia is frequently perceived both in focal and global transient ischemia, augmenting the ischemic brain injury as revealed by experimental and clinical studies. The aim with the current study was to improve the understanding of the pathogenesis behind how concomitant hyperglycemia can augment the cerebral injury seen after cerebral ischemia. To that end we performed a global transcriptome analysis of brains from hyperglycemic and normoglycemic pigs after transient global ischemia.
Project description:Purpose: To gain a better understanding of the molecular mechanisms through which candesartan improves revocery after controlled cortical impact. Methods: We performed a transcriptomic analysis of the ipsilateral hippocampus, thalamus, and hypothalamus at 3 and 29 days post-injury utilizing bulk mRNA-seq. Results: A majority of the differentially expressed genes were identified in the hippocampus at 3 days post injury showing alterations in angiogenesis, interferon signaling, extracellular matrix organization, and DNA replication. At 29 days post injury candesartan treatment reduced genes associated with the inflammatory response. Conclusion: Our data suggests that candesartan has broad actions in the brain after injury and affects different processes in acute and chronic times after injury.
Project description:Microarray analysis of differentially expressed genes from rats undergoing placental ischemia versus health controls Placental ischemia is believed to be an important contributor to human preeclampsia, though the targets induced by the ischemia remain unclear. Chorionic placental tissues from 6 control and 6 placental ischemic reduced uterine perfusion pressure (RUPP) rats were analyzed for gene expression by microarray.
Project description:A drug currently efficient for cerebral stroke therapy is Semax, a synthetic peptide bearing a fragment of ACTH (4â7) and the C-terminal tripeptide Pro-Gly-Pro (PGP) was included to ensure resistance to peptidases.The genome-wide expression changes induced by Semax and PGP in rat brain cortex tissues damaged by focal ischemia were studied using the genome-wide RatRef-12 Expression BeadChip (Illumina, USA), which contains 22,226 genes, according to NCBI. We compared the biochip data obtained at 3 h and 24 h after permanent middle cerebral artery occlusion (pMCAO) in each of the three groups (âischemia,â âischemia + Semax,â and âischemia + PGPâ). The transcriptome profiles were examined at 24 h vs. 3 h after pMCAO in rats that produced ischemic cortical injury and in rats with the same injury treated with Semax or PGP.
