The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome.
BACKGROUND
Early inflammation has been suggested as an important factor contributing to unfavorable prognosis after acute ischemic stroke. The present study aimed to clarify the temporal dynamics of discrete inflammatory markers/mediators for future mechanism-targeting anti-inflammatory strategies in ischemic brain damage.


METHODS
Blood samples of 69 patients with transient ischemic attack or ischemic stroke were taken upon admission and at time points 6, 12 and 24 h, as well as 3 and 7 days after symptom onset for analysis of monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), C-reactive protein (CRP) and the brain damage marker S100B. Clinical scores (modified Rankin Scale, National Institute of Health Stroke Scale) were assessed on day 90.


RESULTS
MCP-1, MMP-9, TIMP-1, IL-6, CRP and S100B showed significantly different time courses depending on stroke outcome. While the levels of IL-6, MCP-1 and MMP-9 increased already a few hours after symptom onset, CRP and S100B gradually rose commencing at 12-24 h. TIMP-1 demonstrated an extended plateau. By multiple linear regression analysis IL-6, MCP-1, TIMP-1 and S100B were determined to be independently related to clinical outcome scores at specific time points.


CONCLUSIONS
Our data show important differences in the early time course of several potential markers for the complex network of inflammation and brain damage after ischemic stroke depending on stroke outcome. This must be considered for any therapeutical approach using anti-inflammatory treatment.
Worthmann
H
H
Department of Neurology, Medical School of Hannover, Hannover, Germany. Worthmann.hans@mh-hannover.de
Tryc
A B
AB
Goldbecker
A
A
Ma
Y T
YT
Tountopoulou
A
A
Hahn
A
A
Dengler
R
R
Lichtinghagen
R
R
Weissenborn
K
K
D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D005260:Female; D005858:Germany; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9