Figure 1: Hyperglycemia and insulin resistance induce free radicals which are responsible for tissue damage. The main sources for free radicals are mitochondrial dysfunction, cytosolic free Ca2+, the vicious cycle between inflammation and OxS, and the activity of advance glycation end products, which promote the innate immune response through their receptors. These conditions produce a significant pool of free radicals, sufficient to cause OxS in the brain. Excessive amounts of ROS/RNS break the delicate regulation of key signaling and effector proteins required to maintain the homeostasis in the brain. ROS: reactive oxygen species; AGEs: advanced glycation end products.