title: Distinct inflammatory responses differentiate cerebral infarct from transient ischaemic attack.
abstract: We previously reported on a 26-year-old patient who presented early during a large and eventually fatal cerebral infarct. Microarray analysis of blood samples from this patient demonstrated initially up-regulated and subsequently down-regulated Granzyme B (GzmB) expression, along with progressive up-regulation of genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase 9 (MMP-9). To confirm these findings, we investigated these parameters in patients with suspected stroke presenting within 6h of symptom onset to a single centre. Blood samples were taken at enrolment, then 1h, 3h and 24h post-enrolment for the examination of cellular, protein and genetic changes. Patients with subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed increased intracellular concentrations of GzmB in all cell populations investigated (CD8+, CD8-and Natural Killer [NK] cells). Infarct patients, however, demonstrated significantly reduced GzmB gene expression and increased circulating MMP-9 and S100A12 levels in contrast to transient ischaemic attack (TIA) patients or healthy controls. Furthermore, a pronounced neutrophilia was noted in the infarct and haemorrhage groups, while TIA patients (n=9) reflected healthy controls (n=10). These findings suggest a spectrum of immune response during stroke. TIA showed few immunological changes in comparison to infarct and haemorrhage, which demonstrated inhibition of GzmB production and a rise in neutrophil numbers and neutrophil-associated mediators. This implies a greater role of the innate immune system. These markers may provide novel targets for inhibition and reduction of secondary injury.
authors.affiliation: Dept. of Emergency Medicine, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: Christopher W L
authors.initials: CW
authors.lastname: Armstrong
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Level 6 MRF Building, 50 Murray St., Perth, WA 6000, Australia; Emergency Medicine, University of Western Australia, Perth, WA, Australia. Electronic address: erika.bosio@uwa.edu.au.
authors.forename: Erika
authors.initials: E
authors.lastname: Bosio
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Level 6 MRF Building, 50 Murray St., Perth, WA 6000, Australia; Emergency Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Neil
authors.affiliation: Dept. of Emergency Medicine, Royal Perth Hospital, Perth, WA, Australia; Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Level 6 MRF Building, 50 Murray St., Perth, WA 6000, Australia; Emergency Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia; Department of Neurology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: Dept. of Emergency Medicine, Royal Perth Hospital, Perth, WA, Australia; Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Level 6 MRF Building, 50 Murray St., Perth, WA 6000, Australia; Emergency Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Fatovich
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002544:Cerebral Infarction / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D053804:Granzymes / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D020300:Intracranial Hemorrhages / Q000175:diagnosis / Q000209:etiology; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D007958:Leukocyte Count; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D000067616:S100A12 Protein / Q000096:biosynthesis / Q000235:genetics; D020521:Stroke / Q000175:diagnosis / Q000209:etiology
chemical_list: D000067616:S100A12 Protein; C509213:GZMB protein, human; D053804:Granzymes; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Granzyme B; Inflammatory markers; MMP-9; Neutrophils; S100A12; Stroke