Monocyte chemoattractant protein–1 predicts outcome and vasospasm following aneurysmal subarachnoid hemorrhage

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Object

Despite efforts to elucidate both the molecular mechanism and the clinical predictors of vasospasm after aneurysmal subarachnoid hemorrhage (ASAH), its pathogenesis remains unclear. Monocyte chemoattractant protein–1 (MCP-1) is a chemokine that has been firmly implicated in the pathophysiology of vasospasm and in neural tissue injury following focal ischemia in both animal models and human studies. The authors hypothesized that MCP-1 would be found in increased concentrations in the blood and cerebrospinal fluid (CSF) of patients with ASAH and would correlate with both outcome and the occurrence of vasospasm.

Methods

Seventy-seven patients who presented with ASAH were prospectively enrolled in this study between July 2001 and May 2002. Using an enzyme-linked immunosorbent assay, MCP-1 levels were measured in serum daily and in CSF when available. The mean serum and CSF MCP-1 concentrations were calculated for each patient throughout the entire hospital stay. Neurological outcome was evaluated at discharge or 14 days posthemorrhage using the modified Rankin Scale. Vasospasm was evaluated on angiography.

Results

The serum MCP-1 concentrations correlated with negative outcome such that a 10% increase in concentration predicted a 25% increase in the probability of a poor outcome, whereas the serum MCP-1 levels did not correlate with vasospasm. Concentrations of MCP-1 in the CSF, however, proved to be significantly higher in patients with angiographically demonstrated vasospasm.

Conclusions

These findings suggest a role for MCP-1 in neurological injury and imply that it may act as a biomarker of poor outcome in the serum and of vasospasm in the CSF.

Abbreviations used in this paper: ASAH = aneurysmal subarachnoid hemorrhage; CSF = cerebrospinal fluid; IL = interleukin; MCP-1 = monocyte chemoattractant protein–1; mRS = modified Rankin Scale; NS = not significant; OR = odds ratio; TNF = tumor necrosis factor.

Article Information

Address correspondence to: Grace H. Kim, M.D., Department of Neurological Surgery, Columbia University, P&S 5-454, 630 West 168th Street, New York, New York 10032. email: ghkim9@yahoo. com.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Bar graph demonstrating serum MCP-1 levels in patients with and without ASAH. A subgroup analysis stratified by Hunt and Hess grade showed that MCP-1 levels were elevated in all groups except the good-grade (Hunt and Hess I and II) group. *p < 0.05, compared with controls.

  • View in gallery

    Bar graph showing CSF MCP-1 levels in all groups. *p < 0.05, compared with controls.

  • View in gallery

    Bar graph revealing serum MCP-1 levels, which predicted a poor outcome on logistic regression analysis with an OR of 1.16 and p < 0.05. Cerebrospinal fluid MCP-1 levels did not predict outcome (data not shown).

  • View in gallery

    Bar graph showing significantly higher CSF MCP-1 levels in medium-grade patients (*p < 0.05), whereas all grades combined and poor-grade patients showed trends toward significance (†p < 0.10).

References

1

Andersson PBPerry VHGordon S: The kinetics and morphological characteristics of the macrophage-microglial response to kainic acid-induced neuronal degeneration. Neuroscience 42:2012141991

2

Barone FCFeuerstein GZ: Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:8198341999

3

Beech JSReckless JMosedale DEGrainger DJWilliams SCMenon DK: Neuroprotection in ischemia-reperfusion injury: an antiinflammatory approach using a novel broad-spectrum chemo-kine inhibitor. J Cereb Blood Flow Metab 21:6836892001

4

Cartier LHartley ODubois-Dauphin MKrause KH: Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48:16422005

5

Chen YHallenbeck JMRuetzler CBol DThomas KBerman NE: Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. J Cereb Blood Flow Me-tab 23:7487552003

6

Colotta FBorré AWang JMTattanelli MMaddalena FPolentarutti N: Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. J Immunol 148:7607651992

7

Dumont ASDumont RJChow MMLin CLCalisaneller TLey KF: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:1231352003

8

Fassbender KHodapp BRossol SBertsch TSchmeck JShütt S: Endothelin-1 in subarachnoid hemorrhage: an acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke 31:297129752000

9

Fernandez ASchmidt JMClaassen JPavlicova MHuddleston DKreiter KT: Fever after subarachnoid hemorrhage. Risk factors and impact on outcome. Neurology 68:101310192007

10

Gaetani PTartara FPignatti PTancioni FRodriguez y Baena RDe Benedetti F: Cisternal CSF levels of cytokines after subarachnoid hemorrhage. Neurol Res 20:3373421998

11

Hughes PMAllegrini PRRudin MPerry VHMir AKWiessner C: Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab 22:3083172002

12

Hunt WEHess RM: Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28:14201968

13

Ingall TJWhisnant JPWiebers DOO'Fallon WM: Has there been a decline in subarachnoid hemorrhage mortality?. Stroke 20:7187241989

14

Johnston SCSelvin SGress DR: The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 50:141314181998

15

Kataoka KTaneda MAsai TKinoshita AIto MKuroda R: Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and un-ruptured cerebral aneurysms. Stroke 30:139614011999

16

Kikuchi TOkuda YKaito NAbe T: Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage. Neurol Res 17:1061081995

17

Kim JS: Cytokines and adhesion molecules in stroke and related diseases. J Neurol Sci 137:69781996

18

Kubota THanda YTsuchida AKaneko MKobayashi HKubota T: The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke 24:199320011993

19

Lerch CYonekawa YMuroi CBjeljac MKeller E: Specialized neurocritical care, severity grade, and outcome of patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care 5:85922006

20

Losy JZaremba J: Monocyte chemoattractant protein-1 is increased in the cerebrospinal fluid of patients with ischemic stroke. Stroke 32:269526962001

21

Macdonald RLWallace MCCoyne TJ: The effect of surgery on the severity of vasospasm. J Neurosurg 80:4334391994

22

Mack WJMocco JHoh DJHuang JChoudhri TFKreiter KT: Outcome prediction with serum intercellular adhesion molecule-1 levels after aneurysmal subarachnoid hemorrhage. J Neurosurg 96:71752002

23

Matz PG: Continued progress in predicting outcome after subarachnoid hemorrhage. Stroke 33:2082092002

24

Mocco JMack WJKim GHLozier APLaufer IKreiter KT: Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 97:5375412002

25

Mocco JRansom ERKomotar RJSchmidt JMSciacca RRMayer SA: Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage. Neurosurgery 59:5295382006

26

Nau R: [Pathophysiology of neuronal injury in bacterial meningitis: concepts and implications.]. Neurologia 18:47532003. (Span)

27

Nimmerjahn AKirchhoff FHelmchen F: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:131413182005

28

Onda HKasuya HTakakura KHori TImaizumi TTakeuchi T: Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage. J Cereb Blood Flow Metab 19:127912881999

29

Provencio JJVora N: Subarachnoid hemorrhage and inflammation: bench to bedside and back. Semin Neurol 25:4354442005

30

Prunell GFSvendgaard NAAlkass KMathiesen T: Inflammation in the brain after experimental subarachnoid hemorrhage. Neurosurgery 56:108210922005

31

Rankine ELHughes PMBotham MSPerry VHFelton LM: Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment. Eur J Neurosci 24:77862006

32

Rollins BJYoshimura TLeonard EJPober JS: Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 136:122912331990

33

Rothoerl RDAxmann CPina ALWoertgen CBrawanski A: Possible role of the C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 18:68722006

34

Schuiling WJde Weerd AWDennesen PJAlgra ARinkel GJ: The simplified acute physiology score to predict outcome in patients with subarachnoid hemorrhage. Neurosurgery 57:2302362005

35

Sercombe RDinh YRGomis P: Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:2272492002

36

Sica AWang JMColotta FDejana EMantovani AOppenheim JJ: Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. J Immunol 144:303430381990

37

Webb DJMonge JCRabelink TJYanagisawa M: Endothelin: new discoveries and rapid progress in the clinic. Trends Pharmacol Sci 19:581998

38

Weber KSNelson PJGrone HJWeber C: Expression of CCR2 by endothelial cells: implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium. Arterioscler Thromb Vasc Biol 19:208520931999

39

Zhou LAzfer ANiu JGraham SChoudhury MAdamski FM: Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ Res 98:117711852006

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