2005/11/21 by Mattias Rickhag, Tadeusz Wieloch, Gunilla Gidö +9 · 6 citations
Neuroscience · Biochemistry, Genetics and Molecular Biology · #Neuroinflammation and Neurodegeneration Mechanisms #MicroRNA in disease regulation #Neurological Disease Mechanisms and Treatments #Biology #Gene expression #Gene expression profiling #Neurotrophin #Transcriptome #Cell biology #Neurotrophic factors #Gene #Receptor #Genetics
paper · pdf · doi:10.1111/j.1471-4159.2005.03508.x
openalex publication_date 2005/11/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02
In order to identify biological processes relevant for cell death and survival in the brain following stroke, the postischemic brain transcriptome was studied by a large-scale cDNA array analysis of three peri-infarct brain regions at eight time points during the first 24 h of reperfusion following middle cerebral artery occlusion in the rat. K-means cluster analysis revealed two distinct biphasic gene expression patterns that contained 44 genes (including 18 immediate early genes), involved in cell signaling and plasticity (i.e. MAP2K7, Sprouty2, Irs-2, Homer1, GPRC5B, Grasp). The first gene induction phase occurred at 0-3 h of reperfusion, and the second at 9-15 h, and was validated by in situ hybridization. Four gene clusters displayed a progressive increase in expression over time and included 50 genes linked to cell motility, lipid synthesis and trafficking (i.e. ApoD, NPC1, G3P-dehydrogenase1, and Choline kinase) or cell death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G-protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling pathways occurs in surviving tissue, concomitant with a progressive and persistent activation of cell proliferation signifying tissue regeneration, which provide the means for cell survival and postischemic brain plasticity.