title: Brain response to traumatic brain injury in wild-type and interleukin-6 knockout mice: a microarray analysis.
abstract: Traumatic injury to the brain is one of the leading causes of injury-related death or disability. Brain response to injury is orchestrated by cytokines, such as interleukin (IL)-6, but the full repertoire of responses involved is not well known. We here report the results obtained with microarrays in wild-type and IL-6 knockout mice subjected to a cryolesion of the somatosensorial cortex and killed at 0, 1, 4, 8 and 16 days post-lesion. Overall gene expression was analyzed by using Affymetrix genechips/oligonucleotide arrays with approximately 12,400 probe sets corresponding to approximately 10,000 different murine genes (MG_U74Av2). A robust, conventional statistical method (two-way anova) was employed to select the genes significantly affected. An orderly pattern of gene responses was clearly detected, with genes being up- or down-regulated at specific timings consistent with the processes involved in the initial tissue injury and later regeneration of the parenchyma. IL-6 deficiency showed a dramatic effect in the expression of many genes, especially in the 1 day post-lesion timing, which presumably underlies the poor capacity of IL-6 knockout mice to cope with brain damage. The results highlight the importance of IL-6 controlling the response of the brain to injury as well as the suitability of microarrays for identifying specific targets worthy of further study.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian Bjørn
authors.initials: CB
authors.lastname: Poulsen
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Rehannah
authors.initials: R
authors.lastname: Borup
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Mario
authors.initials: M
authors.lastname: Cáceres
authors.forename: Albert
authors.initials: A
authors.lastname: Quintana
authors.forename: Amalia
authors.initials: A
authors.lastname: Molinero
authors.forename: Javier
authors.initials: J
authors.lastname: Carrasco
authors.forename: Mercedes
authors.initials: M
authors.lastname: Giralt
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015850:Interleukin-6