Immune Cell-Derived Free Radicals in Acute Brain Injury

Oxidative stress, which generates reactive oxygen species (ROS), plays an important role after acute brain injuries, including transient cerebral ischemia. Brain injuries like ischemic–reperfusion result in a surge of excess oxygen that leads to generation of free radicals. Free radicals are present at low levels in the normal state where they play a critical role in signaling pathways. Antioxidants help in maintaining the redox level in the cells, but during an insult this homeostasis is disturbed resulting in excessive ROS. Mitochondrial ROS are among the main intracellular ROS. Cerebral ischemia triggers inflammation in response to injury, which also leads to the generation of free radicals and eventually to neuronal cell death. Studies using genetically manipulated animals where antioxidant genes are overexpressed or knocked down show the key role that ROS play in ischemia. Oxidative stress affects the injured area in a multifaceted way. It activates apoptotic markers, inflammatory mediators including cytokines and chemokines, and transcriptional activators. Therefore, it has a significant function in cell death and survival signaling cascades. Several recent reports have demonstrated the various effects of ROS generation and its link to the inflammatory response after ischemia. In this chapter, we present an overview of these mechanisms that have been elucidated, focusing on the damaging effects of ROS and their crucial role in inflammation after stroke.