TY - JOUR
T1 - Distinct inflammatory responses differentiate cerebral infarct from transient ischaemic attack
AU - Armstrong, Christopher W L
AU - Bosio, Erika
AU - Neil, Claire
AU - Brown, Simon G A
AU - Hankey, Graeme J.
AU - Fatovich, Daniel M.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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 6 h of symptom onset to a single centre. Blood samples were taken at enrolment, then 1 h, 3 h and 24 h 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.
AB - 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 6 h of symptom onset to a single centre. Blood samples were taken at enrolment, then 1 h, 3 h and 24 h 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.
KW - Granzyme B
KW - Inflammatory markers
KW - MMP-9
KW - Neutrophils
KW - S100A12
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85006117564&partnerID=8YFLogxK
U2 - 10.1016/j.jocn.2016.09.011
DO - 10.1016/j.jocn.2016.09.011
M3 - Article
C2 - 27697435
AN - SCOPUS:85006117564
VL - 35
SP - 97
EP - 103
JO - Journal of Clinical Neuroscience
JF - Journal of Clinical Neuroscience
SN - 0967-5868
ER -