title: Changes in differential gene expression during a fatal stroke.
abstract: We present a young woman (with an identical twin sister) who arrived at the Emergency Department (ED) within 1 hour of her initial stroke symptoms. Previous microarray studies have demonstrated differential expression of multiple genes between stroke patients and healthy controls. However, for many of these studies there is a significant delay between the initial symptoms and collection of blood samples, potentially leaving the important early activators/regulators of the inflammatory response unrecognised. Blood samples were collected from the patient for an analysis of differential gene expression over time during the evolution of a fatal stroke. The time points for blood collection were ED arrival (T0) and 1, 3 and 24 hours post ED arrival (T1, T3 and T24). This was compared to her identical twin and an additional two age and sex-matched healthy controls. When compared to the controls, the patient had 12 mRNA that were significantly upregulated at T0, and no downregulated mRNA (with a cut off fold change value ±1.5). Of the 12 upregulated mRNA at T0, granzyme B demonstrated the most marked upregulation on arrival, with expression steadily declining over time, whereas S100 calcium-binding protein A12 (S100A12) gene expression increased from T0 to T24, remaining >two-fold above that in the healthy controls at T24. Other genes, such as matrix metalloproteinase 9, high mobility group box 2 and interleukin-18 receptor I were not upregulated at T0, but they demonstrated clear upregulation from T1–T3, with gene expression declining by T24. A greater understanding of the underlying immunopathological mechanisms that are involved during the evolution of ischaemic stroke may help to distinguish between patients with stroke and stroke mimics.
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Stone
authors.forename: Christopher
authors.initials: C
authors.lastname: Armstrong
authors.forename: Pauline E
authors.initials: PE
authors.lastname: van Eeden
authors.forename: Glenn
authors.initials: G
authors.lastname: Arendts
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Fatovich
mesh_terms: D000328:Adult; D017809:Fatal Outcome; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators