Cerebrovascular Disease in Type 1 Diabetes: Role of Oxidative Stress

Abstract

Type 1 diabetes mellitus (T1D) is characterized by an elevation of blood glucose (hyperglycemia), a decrease in circulating levels of insulin, and the development of macro- and microvascular abnormalities. Hyperglycemia appears to be the primary determinant of the structural, functional, and biochemical abnormalities observed in large and small blood vessels of various organ systems during T1D. Hyperglycemia activates various cellular pathways/networks that undoubtedly produce/contribute to endothelial/vascular dysfunction via an increase in oxidative stress. Given that the structural, functional, and biochemical integrity of the brain depend upon the critical coupling between neural activity and cerebral blood flow (neurovascular coupling), alterations in this coupling by T1D could contribute to dysfunction of the blood–brain barrier and/or responses of large and small cerebral blood vessels in response to various stimuli. These abnormalities could then contribute to the pathogenesis of cognitive dysfunction and/or ischemic stroke observed in patients suffering with T1D. The purpose of this chapter is to discuss the role of oxidative stress in impaired cerebrovascular function during T1D. We will discuss critical pathways that produce oxidants and the potential role of these oxidants in the pathogenesis of cerebrovascular dysfunction and perhaps ischemic stroke during T1D. We suggest that a greater understanding regarding the nature of oxidants and antioxidants, and their sources, could lead to new and targeted therapeutic approaches for the treatment of cognitive dysfunction and stroke observed in diabetic subjects.