Brain response to traumatic brain injury in wild-type and interleukin-6 knockout mice: A microarray analysis

Christian Bjørn Poulsen, Milena Penkowa, Rehannah Borup, Finn Cilius Nielsen, Mario Cáceres, Albert Quintana, Amalia Molinero, Javier Carrasco, Mercedes Giralt, Juan Hidalgo*

*Autor corresponent d’aquest treball

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Resum

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 ∼12 400 probe sets corresponding to ∼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.
Idioma originalEnglish
Pàgines (de-a)417-432
RevistaJournal of Neurochemistry
Volum92
DOIs
Estat de la publicacióPublicada - 1 de gen. 2005

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