Role of Endogenous Granulocyte-Macrophage Colony Stimulating Factor Following Stroke and Relationship to Neurological Outcome

Miriam      Navarro-Sobrino; Anna      Rosell; Anna      Penalba; Marc      Ribo; Jose      Alvarez-Sabin; Israel      Fernandez-Cadenas; Joan      Montaner

Abstract

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a proinflammatory cytokine with neuroprotective and angiogenic properties demonstrated in animal models of cerebral ischemia but its role in human ischemic stroke is still unknown. Thus, our aim is to determine human GM-CSF plasma level in control subjects and stroke patients and its relationship to clinical outcome. Forty-three patients with middle cerebral artery occlusion who received thrombolytic therapy within the first three hours of stroke onset and nineteen healthy controls were included. Blood samples were drawn before tissue plasminogen activator (t-PA) treatment. In a group of thirteen strokes blood samples were also obtained one hour after t-PA treatment, at 24 hours of symptoms onset, at discharge and at three months. GM-CSF levels were determined by enzyme-linked immunosorbent assay (ELISA). Stroke severity and neurological outcome were assessed by National Institute of Health Stroke Scale (NIHSS) and functional outcome was scored by modified Rankin Scale (mRS) at 3 months. Baseline GM-CSF level was significantly higher in stroke patients than in healthy controls (17.8 pg/ml vs. 12.8 pg/ml); p < 0.0001 and was positively correlated with NIHSS score at 12 hours (R=0.3, p=0.03). No association was detected with functional status at three months measured by mRS. Temporary profile of GM-CSF level in stroke patients gradually decreases from admission to three months. Higher plasma endogenous GMCSF level is found in stroke patients compared to controls. However, no relation was found with a better outcome. Further research is necessary for elucidating the role of GM-CSF in ischemic stroke.

Keywords: Stroke, neuroprotection, angiogenesis, GM-CSF, thrombolysis, hematopoietic cytokines

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