title: Temporal Profile of MicroRNA Expression in Contused Cortex after Traumatic Brain Injury in Mice.
abstract: MicroRNAs (miRNAs) were recently identified as important regulators of gene expression under a wide range of physiological and pathophysiological conditions. Thus, they may represent a novel class of molecular targets for the management of traumatic brain injury (TBI). In this study, we investigated the temporal profile of miRNA expression during the development of secondary brain damage after experimental TBI. For this purpose, we used a controlled cortical impact model in C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression in the traumatized cortex by microarray analysis during the development of secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780 mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of these, 158 miRNAs were significantly upregulated or downregulated in TBI compared with sham-operated animals, and 52 miRNAs increased more than twofold. We validated the upregulation of five of the most differentially expressed miRNAs (miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially expressed miRNA after TBI, was further investigated by in situ hybridization and was found to be upregulated in neurons within the traumatic penumbra. This study gives a comprehensive picture of miRNA expression levels during secondary contusion expansion after TBI and may pave the way for the identification of novel targets for the management of brain trauma.
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .|2 Institute for Stroke and Dementia Research, University of Munich Medical Center , Munich, Germany .
authors.forename: Lilja
authors.initials: L
authors.lastname: Meissner
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Micaela
authors.initials: M
authors.lastname: Gallozzi
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .|2 Institute for Stroke and Dementia Research, University of Munich Medical Center , Munich, Germany .
authors.forename: Matilde
authors.initials: M
authors.lastname: Balbi
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwarzmaier
authors.affiliation: 2 Institute for Stroke and Dementia Research, University of Munich Medical Center , Munich, Germany .
authors.forename: Steffen
authors.initials: S
authors.lastname: Tiedt
authors.affiliation: 3 Institute for Surgical Research, University of Munich Medical Center , Munich, Germany .
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Terpolilli
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .|2 Institute for Stroke and Dementia Research, University of Munich Medical Center , Munich, Germany .|4 Munich Cluster of Systems Neurology (Synergy), Munich, Germany .
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D000070624:Brain Contusion / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D035683:MicroRNAs
keywords: controlled cortical impact; miRNA; microarray; mouse; penumbra; traumatic brain injury