Immune Cell-Derived Free Radicals in Acute Brain Injury

  • Purnima Narasimhan
  • Hiroyuki Sakata
  • Joo Eun Jung
  • Tatsuro Nishi
  • Takuma Wakai
  • Carolina M. Maier
  • Pak H. Chan
Part of the Springer Series in Translational Stroke Research book series (SSTSR, volume 6)


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.


Reactive Oxygen Species Cerebral Ischemia Reactive Oxygen Species Generation Neuronal Cell Death Acute Brain Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


cyt c

Cytochrome c


4′,6 Diamidino-2-phenylindole


Glutathione peroxidase






Intercellular adhesion molecule 1






Middle cerebral artery occlusion


Monocyte chemoattractant protein-1


Macrophage inflammatory protein-1α


Modified neurologic severity scores


Nuclear factor-kappa B


Neuronal nitric oxide synthase


Nitric oxide




NADPH oxidase


NADH quinone oxidoreductase


Neural stem cells


Superoxide anion


Optical density


Hydroxyl ion






Reactive oxygen species


Standard deviation


Small interfering RNA


Superoxide dismutase


Signal transducer and activator of transcription 3




Tumor necrosis factor-α


Terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling





This work was supported by NIH grants PO1 NS014543, RO1 NS025372, and RO1 NS038653, and by the James R. Doty Endowment.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Purnima Narasimhan
    • 1
  • Hiroyuki Sakata
    • 1
  • Joo Eun Jung
    • 1
  • Tatsuro Nishi
    • 1
  • Takuma Wakai
    • 1
  • Carolina M. Maier
    • 1
  • Pak H. Chan
    • 1
  1. 1.Stanford University School of MedicineStanfordUSA

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