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.
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.
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.
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.
BeechJSRecklessJMosedaleDEGraingerDJWilliamsSCMenonDK: Neuroprotection in ischemia-reperfusion injury: an antiinflammatory approach using a novel broad-spectrum chemo-kine inhibitor. J Cereb Blood Flow Metab21:683–6892001
ChenYHallenbeckJMRuetzlerCBolDThomasKBermanNE: 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-tab23:748–7552003
KataokaKTanedaMAsaiTKinoshitaAItoMKurodaR: Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and un-ruptured cerebral aneurysms. Stroke30:1396–14011999
RankineELHughesPMBothamMSPerryVHFeltonLM: Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment. Eur J Neurosci24:77–862006
RothoerlRDAxmannCPinaALWoertgenCBrawanskiA: Possible role of the C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol18:68–722006
WeberKSNelsonPJGroneHJWeberC: Expression of CCR2 by endothelial cells: implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium. Arterioscler Thromb Vasc Biol19:2085–20931999