Granulocyte-macrophage colony-stimulating factor as an arteriogenic factor in the treatment of ischaemic stroke

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces arteriogenic growth of collateral vessels after occlusion of cardiac or peripheral arteries. Recently, evidence has been provided that arteriogenesis also occurs in the brain under conditions of reduced arterial blood supply. Hemispheric hypoperfusion induced by unilateral carotid and bilateral vertebral artery occlusion (three-vessel occlusion, [3-VO]) led to the growth of the anterior and posterior segments of the circle of Willis, which is the main collateral pathway between the origins of the anterior, middle and posterior cerebral arteries. GM-CSF applied subcutaneously at daily doses of 40 mu g(.)kg(-1) resulted in the marked acceleration of this process. Within one week after the onset of treatment, the diameter of the posterior segment of the circle of Willis enlarged to 170% of control, blood flow and the haemodynamic reserve capacity of the brain returned to normal, and haemodynamic stroke, induced after 3-VO by systemic hypotension, was greatly alleviated. GM-CSF-induced stimulation of arteriogenesis in the hypoperfused brain thus provides powerful protection against ischaemic stroke.