Brain response to traumatic brain injury in wild-type and interleukin-6 knockout mice: a microarray analysis.
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.
Poulsen
Christian Bjørn
CB
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Penkowa
Milena
M
Borup
Rehannah
R
Nielsen
Finn Cilius
FC
Cáceres
Mario
M
Quintana
Albert
A
Molinero
Amalia
A
Carrasco
Javier
J
Giralt
Mercedes
M
Hidalgo
Juan
J
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
D015850:Interleukin-6