title: The genomic profile of the cerebral cortex after closed head injury in mice: effects of minocycline.
abstract: Microarray analysis was used to delineate gene expression patterns and profile changes following traumatic brain injury (TBI) in mice. A parallel microarray analysis was carried out in mice with TBI that were subsequently treated with minocycline, a drug proposed as a neuroprotectant in other neurological disorders. The aim of this comparison was to identify pathways that may be involved in secondary injury processes following TBI and potential specific pathways that could be targeted with second generation therapeutics for the treatment of neurotrauma patients. Gene expression profiles were measured with the compugen long oligo chip and real-time PCR was used to validate microarray findings. A pilot study of effect of minocycline on gene expression following TBI was also carried out. Gene ontology comparison analysis of sham TBI and minocycline treated brains revealed biological pathways with more genes differentially expressed than predicted by chance. Among 495 gene ontology categories, the significantly different gene ontology groups included chemokines, genes involved in cell surface receptor-linked signal transduction and pro-inflammatory cytokines. Expression levels of some key genes were validated by real-time quantitative PCR. This study confirms that multiple regulatory pathways are affected following brain injury and demonstrates for the first time that specific genes and molecular networks are affected by minocycline following brain injury.
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, VIC, 3010, Australia. pcrack@unimelb.edu.au
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.forename: Jodee
authors.initials: J
authors.lastname: Gould
authors.forename: Nicole
authors.initials: N
authors.lastname: Bye
authors.forename: Shelley
authors.initials: S
authors.lastname: Ross
authors.forename: Uğur
authors.initials: U
authors.lastname: Ali
authors.forename: Mark D
authors.initials: MD
authors.lastname: Habgood
authors.forename: Cristina
authors.initials: C
authors.lastname: Morganti-Kossman
authors.forename: Norman R
authors.initials: NR
authors.lastname: Saunders
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hertzog
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D030541:Databases, Genetic; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D016489:Head Injuries, Closed / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline