Distinct inflammatory responses differentiate cerebral infarct from transient ischaemic attack

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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 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.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalJournal of Clinical Neuroscience
Volume35
DOIs
Publication statusPublished - 1 Jan 2017

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Transient Ischemic Attack
Granzymes
Stroke
Matrix Metalloproteinase 9
Neutrophils
Hemorrhage
Calcium-Binding Proteins
compound A 12
Microarray Analysis
Natural Killer Cells
Immune System
Up-Regulation
Gene Expression
Wounds and Injuries
Population
Genes
Proteins

Cite this

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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 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.",
keywords = "Granzyme B, Inflammatory markers, MMP-9, Neutrophils, S100A12, Stroke",
author = "Armstrong, {Christopher W L} and Erika Bosio and Claire Neil and Brown, {Simon G A} and Hankey, {Graeme J.} and Fatovich, {Daniel M.}",
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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.

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KW - Inflammatory markers

KW - MMP-9

KW - Neutrophils

KW - S100A12

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U2 - 10.1016/j.jocn.2016.09.011

DO - 10.1016/j.jocn.2016.09.011

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VL - 35

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JO - Journal of Clinical Neuroscience

JF - Journal of Clinical Neuroscience

SN - 0967-5868

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