title: Age-specific transcriptional response to stroke.
abstract: Increased age is a major risk factor for stroke incidence and post-ischemic mortality. To develop age-adjusted therapeutic interventions, a clear understanding of the complexity of age-related post-ischemic mechanisms is essential. Transient occlusion of the middle cerebral artery--a model that closely resembles human stroke--was used to induce cerebral infarction in mice of 4 different ages (2, 9, 15, 24 months). By using Illumina cDNA microarrays and quantitative PCR we detected a distinct age-dependent response to stroke involving 350 differentially expressed genes. Our analyses also identified 327 differentially expressed genes that responded to stroke in an age-independent manner. These genes are involved in different aspects of the inflammatory and immune response, oxidative stress, cell cycle activation and/or DNA repair, apoptosis, cytoskeleton reorganization and/or astrogliosis, synaptic plasticity and/or neurotransmission, and depressive disorders and/or dopamine-, serotonin-, GABA-signaling. In agreement with our earlier work, aged brains displayed an attenuated inflammatory and immune response (Sieber et al., 2011) and a reduced impairment of post-stroke synaptic plasticity. Our data also revealed a distinct age-related susceptibility for post-ischemic depression, the most common neuropsychiatric consequence of stroke, which has a major influence on functional outcome.
authors: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors: Matthias W
authors: MW
authors: Sieber
authors: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors: Madlen
authors: M
authors: Guenther
authors: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors: Nadine
authors: N
authors: Jaenisch
authors: Biocontrol Jena GmbH, Jena, Germany.
authors: Daniela
authors: D
authors: Albrecht-Eckardt
authors: Department of Mechanical and Process Engineering, Furtwangen University, Villingen-Schwenningen, Germany.
authors: Matthias
authors: M
authors: Kohl
authors: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany; CSCC, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors: Otto W
authors: OW
authors: Witte
authors: Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany. Electronic address: christiane.frahm@med.uni-jena.de.
authors: Christiane
authors: C
authors: Frahm
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000503:physiopathology; D002453:Cell Cycle / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D003866:Depressive Disorder / Q000235:genetics; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009416:Nerve Regeneration; D009473:Neuronal Plasticity / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D013569:Synapses / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics*
keywords: Aging; Depression; Inflammation; MCAO