A Mechanistic Justification for a Trial of Insulin Infusion Therapy

Background and Purpose—Hyperglycemia is associated with increased mortality and morbidity in acute ischemic stroke. Summary of Review—Hyperglycemia induces a pro-oxidative and proinflammatory state that can cause direct neuronal toxicity. Hyperglycemia-mediated increase in matrix metalloproteinase-9 can cause neuronal damage by an increase in cerebral edema. Moreover, hyperglycemia may be responsible for a procoagulant state that can further compromise blood supply to the penumbral areas in acute ischemic stroke. Insulin infusion has an effect that is opposite to that of hyperglycemia. It not only lowers blood glucose levels but also exerts an antioxidant and anti-inflammatory effect. Insulin also improves NO production and results in improved blood circulation to the ischemic areas. This article focuses on the potential mechanisms underlying the injurious effects of glucose and the beneficial effects of insulin. Conclusions—In the absence of other potential beneficial therapies, there is an urgency to institute trials with insulin infusion in acute ischemic stroke. (Stroke. 2006;37:267-273.)