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Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke

Authors: Christopher Beer, David Blacker, Michael Bynevelt, Graeme J Hankey, Ian B Puddey

Published in: Journal of Neuroinflammation | Issue 1/2010

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Abstract

Background

Vascular dysfunction and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke. However acute inflammation and vascular dysfunction may simply be markers of an acute phase response to cerebral injury, reflecting the size of the cerebral lesion. We aimed to determine if systemic markers of vascular dysfunction and inflammation are independently associated with concentrations of the astroglial protein S100B, a marker of brain injury, in participants with acute ischaemic stroke.

Methods

Fifty-seven men and women recruited within 96 hours of acute ischaemic stroke at two tertiary hospitals participated in this cross sectional observational study. Clinical, imaging (stroke lesions area measured with perfusion CT) and laboratory data were the independent variables and co-variates. The outcome variable was serum S100B concentration, analysed by multivariate regression.

Results

High sensitivity-CRP (B = 0.41) and lesion area (B = 0.69) were independently associated with S100B concentration (R2 = 0.75, p < 0.01). Other variables with significant univariate associations with S100B concentration were not independently associated with S100B concentration in the final multivariate model.

Conclusion

The degree of systemic inflammation is associated with S100B concentration in acute ischaemic stroke, independent of the size of the ischaemic lesion.
Literature
1.
go back to reference Cherian P, Hankey GJ, Eikelboom JW, Thom J, Baker RI, McQuillan A, Staton J, Yi Q: Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Stroke. 2003, 34: 2132-2137. 10.1161/01.STR.0000086466.32421.F4.CrossRefPubMed Cherian P, Hankey GJ, Eikelboom JW, Thom J, Baker RI, McQuillan A, Staton J, Yi Q: Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Stroke. 2003, 34: 2132-2137. 10.1161/01.STR.0000086466.32421.F4.CrossRefPubMed
2.
go back to reference Dirnagl U, Iadecola C, Moskowitz MA: Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999, 22: 391-397. 10.1016/S0166-2236(99)01401-0.CrossRefPubMed Dirnagl U, Iadecola C, Moskowitz MA: Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999, 22: 391-397. 10.1016/S0166-2236(99)01401-0.CrossRefPubMed
3.
go back to reference Lip GYH, Blann AD, Farooqi IS, Zarifis J, Sagar G, Beevers DG: Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project. Blood Coagulation & Fibrinolysis. 2002, 13: 339-347.CrossRef Lip GYH, Blann AD, Farooqi IS, Zarifis J, Sagar G, Beevers DG: Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project. Blood Coagulation & Fibrinolysis. 2002, 13: 339-347.CrossRef
4.
go back to reference Sanchez-Moreno C, Dashe JF, Scott T, Thaler D, Folstein MF, Martin A: Decreased Levels of Plasma Vitamin C and Increased Concentrations of Inflammatory and Oxidative Stress Markers After Stroke. Stroke. 2004, 35: 163-168. 10.1161/01.STR.0000105391.62306.2E.CrossRefPubMed Sanchez-Moreno C, Dashe JF, Scott T, Thaler D, Folstein MF, Martin A: Decreased Levels of Plasma Vitamin C and Increased Concentrations of Inflammatory and Oxidative Stress Markers After Stroke. Stroke. 2004, 35: 163-168. 10.1161/01.STR.0000105391.62306.2E.CrossRefPubMed
5.
go back to reference van Kooten F, Ciabattoni G, Patrono C, Dippel DWJ, Koudstaal PJ: Platelet Activation and Lipid Peroxidation in Patients With Acute Ischemic Stroke. Stroke. 1997, 28: 1557-1563.CrossRefPubMed van Kooten F, Ciabattoni G, Patrono C, Dippel DWJ, Koudstaal PJ: Platelet Activation and Lipid Peroxidation in Patients With Acute Ischemic Stroke. Stroke. 1997, 28: 1557-1563.CrossRefPubMed
6.
go back to reference Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, del Zoppo GJ, Hallenbeck JM, Rothwell NJ, Hopkins SJ, Tyrrell PJ: Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol. 2004, 4: 2-10.1186/1471-2377-4-2.PubMedCentralCrossRefPubMed Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, del Zoppo GJ, Hallenbeck JM, Rothwell NJ, Hopkins SJ, Tyrrell PJ: Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol. 2004, 4: 2-10.1186/1471-2377-4-2.PubMedCentralCrossRefPubMed
7.
go back to reference Kelly PJ, Morrow JD, Ning M, Koroshetz W, Lo EH, Terry E, Milne GL, Hubbard J, Lee H, Stevenson E, et al: Oxidative Stress and Matrix Metalloproteinase-9 in Acute Ischemic Stroke: The Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) Study. Stroke. 2008, 39: 100-104. 10.1161/STROKEAHA.107.488189.CrossRefPubMed Kelly PJ, Morrow JD, Ning M, Koroshetz W, Lo EH, Terry E, Milne GL, Hubbard J, Lee H, Stevenson E, et al: Oxidative Stress and Matrix Metalloproteinase-9 in Acute Ischemic Stroke: The Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) Study. Stroke. 2008, 39: 100-104. 10.1161/STROKEAHA.107.488189.CrossRefPubMed
8.
go back to reference Eikelboom JW, Hankey GJ, Baker RI, McQuillan A, Thom J, Staton J, Cole V, Yi Q: C-reactive protein in ischemic stroke and its etiologic subtypes. Journal of Stroke and Cerebrovascular Diseases. 2003, 12: 74-81. 10.1053/jscd.2003.16.CrossRefPubMed Eikelboom JW, Hankey GJ, Baker RI, McQuillan A, Thom J, Staton J, Cole V, Yi Q: C-reactive protein in ischemic stroke and its etiologic subtypes. Journal of Stroke and Cerebrovascular Diseases. 2003, 12: 74-81. 10.1053/jscd.2003.16.CrossRefPubMed
9.
go back to reference Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR: C-Reactive Protein and Outcome After Ischemic Stroke. Stroke. 1999, 30: 981-985.CrossRefPubMed Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR: C-Reactive Protein and Outcome After Ischemic Stroke. Stroke. 1999, 30: 981-985.CrossRefPubMed
10.
go back to reference Audebert HJ, Pellkofer TS, Wimmer ML, Haberl RL: Progression in lacunar stroke is related to elevated acute phase parameters. Eur Neurol. 2004, 51: 125-131. 10.1159/000077012.CrossRefPubMed Audebert HJ, Pellkofer TS, Wimmer ML, Haberl RL: Progression in lacunar stroke is related to elevated acute phase parameters. Eur Neurol. 2004, 51: 125-131. 10.1159/000077012.CrossRefPubMed
11.
go back to reference Herrmann M, Ehrenreich H: Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci. 2003, 21: 177-190.PubMed Herrmann M, Ehrenreich H: Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci. 2003, 21: 177-190.PubMed
12.
go back to reference Rothermundt M, Peters M, Prehn JH, Arolt V: S100B in brain damage and neurodegeneration. Microsc Res Tech. 2003, 60: 614-632. 10.1002/jemt.10303.CrossRefPubMed Rothermundt M, Peters M, Prehn JH, Arolt V: S100B in brain damage and neurodegeneration. Microsc Res Tech. 2003, 60: 614-632. 10.1002/jemt.10303.CrossRefPubMed
13.
go back to reference Bamford J, Sandercock P, Dennis M, Burn J, Warlow C: Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991, 337: 1521-1526. 10.1016/0140-6736(91)93206-O.CrossRefPubMed Bamford J, Sandercock P, Dennis M, Burn J, Warlow C: Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991, 337: 1521-1526. 10.1016/0140-6736(91)93206-O.CrossRefPubMed
14.
go back to reference Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, et al: Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989, 20: 864-870.CrossRefPubMed Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, et al: Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989, 20: 864-870.CrossRefPubMed
15.
go back to reference Shah S, Vanclay F, Cooper B: Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol. 1989, 42: 703-709. 10.1016/0895-4356(89)90065-6.CrossRefPubMed Shah S, Vanclay F, Cooper B: Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol. 1989, 42: 703-709. 10.1016/0895-4356(89)90065-6.CrossRefPubMed
16.
go back to reference Bamford JM, Sandercock PA, Warlow CP, Slattery J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1989, 20: 828.CrossRefPubMed Bamford JM, Sandercock PA, Warlow CP, Slattery J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1989, 20: 828.CrossRefPubMed
17.
go back to reference Mori TA, Croft KD, Puddey IB, Beilin LJ: An improved method for the measurement of urinary and plasma F2-isoprostanes using gas chromatography-mass spectrometry. Anal Biochem. 1999, 268: 117-125. 10.1006/abio.1998.3037.CrossRefPubMed Mori TA, Croft KD, Puddey IB, Beilin LJ: An improved method for the measurement of urinary and plasma F2-isoprostanes using gas chromatography-mass spectrometry. Anal Biochem. 1999, 268: 117-125. 10.1006/abio.1998.3037.CrossRefPubMed
18.
go back to reference Jones SC, Bilous M, Winship S, Finn P, Goodwin J: Validation of the OSCAR 2 oscillometric 24-hour ambulatory blood pressure monitor according to the International Protocol for the validation of blood pressure measuring devices. Blood Press Monit. 2004, 9: 219-223. 10.1097/00126097-200408000-00007.CrossRefPubMed Jones SC, Bilous M, Winship S, Finn P, Goodwin J: Validation of the OSCAR 2 oscillometric 24-hour ambulatory blood pressure monitor according to the International Protocol for the validation of blood pressure measuring devices. Blood Press Monit. 2004, 9: 219-223. 10.1097/00126097-200408000-00007.CrossRefPubMed
19.
go back to reference Goodwin J, Bilous M, Winship S, Finn P, Jones SC: Validation of the Oscar 2 oscillometric 24-h ambulatory blood pressure monitor according to the British Hypertension Society protocol. Blood Press Monit. 2007, 12: 113-117. 10.1097/MBP.0b013e3280acab1b.CrossRefPubMed Goodwin J, Bilous M, Winship S, Finn P, Jones SC: Validation of the Oscar 2 oscillometric 24-h ambulatory blood pressure monitor according to the British Hypertension Society protocol. Blood Press Monit. 2007, 12: 113-117. 10.1097/MBP.0b013e3280acab1b.CrossRefPubMed
20.
go back to reference Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, Badiwala MV, Mickle DA, Weisel RD, Fedak PW, et al: C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation. 2004, 109: 2058-2067. 10.1161/01.CIR.0000127577.63323.24.CrossRefPubMed Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, Badiwala MV, Mickle DA, Weisel RD, Fedak PW, et al: C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation. 2004, 109: 2058-2067. 10.1161/01.CIR.0000127577.63323.24.CrossRefPubMed
21.
go back to reference Worthmann H, Tryc AB, Goldbecker A, Ma YT, Tountopoulou A, Hahn A, Dengler R, Lichtinghagen R, Weissenborn K: The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome. Cerebrovasc Dis. 2010, 30: 85-92. 10.1159/000314624.CrossRefPubMed Worthmann H, Tryc AB, Goldbecker A, Ma YT, Tountopoulou A, Hahn A, Dengler R, Lichtinghagen R, Weissenborn K: The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome. Cerebrovasc Dis. 2010, 30: 85-92. 10.1159/000314624.CrossRefPubMed
22.
go back to reference Sienkiewicz-Jarosz H, Galecka-Wolska M, Bidzinski A, Turzynska D, Sobolewska A, Lipska B, Plaznik A, Ryglewicz D: Predictive value of selected biochemical markers of brain damage for functional outcome in ischaemic stroke patients. Neurol Neurochir Pol. 2009, 43: 126-133.PubMed Sienkiewicz-Jarosz H, Galecka-Wolska M, Bidzinski A, Turzynska D, Sobolewska A, Lipska B, Plaznik A, Ryglewicz D: Predictive value of selected biochemical markers of brain damage for functional outcome in ischaemic stroke patients. Neurol Neurochir Pol. 2009, 43: 126-133.PubMed
23.
go back to reference Sen J, Belli A: S100B in neuropathologic states: the CRP of the brain?. J Neurosci Res. 2007, 85: 1373-1380. 10.1002/jnr.21211.CrossRefPubMed Sen J, Belli A: S100B in neuropathologic states: the CRP of the brain?. J Neurosci Res. 2007, 85: 1373-1380. 10.1002/jnr.21211.CrossRefPubMed
24.
go back to reference Portela LV, Brenol JC, Walz R, Bianchin M, Tort AB, Canabarro UP, Beheregaray S, Marasca JA, Xavier RM, Neto EC, et al: Serum S100B levels in patients with lupus erythematosus: preliminary observation. Clin Diagn Lab Immunol. 2002, 9: 164-166.PubMedCentralPubMed Portela LV, Brenol JC, Walz R, Bianchin M, Tort AB, Canabarro UP, Beheregaray S, Marasca JA, Xavier RM, Neto EC, et al: Serum S100B levels in patients with lupus erythematosus: preliminary observation. Clin Diagn Lab Immunol. 2002, 9: 164-166.PubMedCentralPubMed
25.
go back to reference Gross S, Homan van der Heide JJ, van Son WJ, Gans RO, Foell D, Navis G, Bakker SJ: Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients. Med Sci Monit. 2010, 16: CR318-324.PubMed Gross S, Homan van der Heide JJ, van Son WJ, Gans RO, Foell D, Navis G, Bakker SJ: Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients. Med Sci Monit. 2010, 16: CR318-324.PubMed
26.
go back to reference Johnston KC, Wagner DP, Haley EC, Connors AF: Combined clinical and imaging information as an early stroke outcome measure. Stroke. 2002, 33: 466-472. 10.1161/hs0202.102881.PubMedCentralCrossRefPubMed Johnston KC, Wagner DP, Haley EC, Connors AF: Combined clinical and imaging information as an early stroke outcome measure. Stroke. 2002, 33: 466-472. 10.1161/hs0202.102881.PubMedCentralCrossRefPubMed
27.
go back to reference Adams HP, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, Woolson RF, Hansen MD: Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999, 53: 126-131.CrossRefPubMed Adams HP, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, Woolson RF, Hansen MD: Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999, 53: 126-131.CrossRefPubMed
28.
go back to reference Foerch C, Singer OC, Neumann-Haefelin T, du Mesnil de Rochemont R, Steinmetz H, Sitzer M: Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. Arch Neurol. 2005, 62: 1130-1134. 10.1001/archneur.62.7.1130.CrossRefPubMed Foerch C, Singer OC, Neumann-Haefelin T, du Mesnil de Rochemont R, Steinmetz H, Sitzer M: Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. Arch Neurol. 2005, 62: 1130-1134. 10.1001/archneur.62.7.1130.CrossRefPubMed
29.
go back to reference Pleines UE, Morganti-Kossmann MC, Rancan M, Joller H, Trentz O, Kossmann T: S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury. J Neurotrauma. 2001, 18: 491-498. 10.1089/089771501300227297.CrossRefPubMed Pleines UE, Morganti-Kossmann MC, Rancan M, Joller H, Trentz O, Kossmann T: S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury. J Neurotrauma. 2001, 18: 491-498. 10.1089/089771501300227297.CrossRefPubMed
Metadata
Title
Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke
Authors
Christopher Beer
David Blacker
Michael Bynevelt
Graeme J Hankey
Ian B Puddey
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-71

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