The Role of Reactive Oxygen Species in the Pathogenesis of Traumatic Brain Injury

  • Esther Shohami
  • Ron Kohen
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


Traumatic brain injury (TBI) is a major cause of death in the young age group and leads to persisting neurological impairment in many of its victims. TBI involves a primary mechanical impact followed by the development of vasogenic and cytotoxic edema and impairment of energy metabolism and ionic homeostasis. Primary injury sets in motion a cascade of events that activate molecular and cellular responses. The relatively rapid process of primary cell death is followed by secondary degeneration of adjacent neurons having escaped the initial insult. The primary death of brain cells concomitantly also causes accumulation of harmful physiological substances such as glutamate, reactive oxygen species (ROS), and pro-inflammatory cytokines, creating a toxic environment for neighboring neurons and resulting in functional deficits. The mammalian brain is vulnerable to oxidative stress because of the high oxygen consumption needed for maintaining neuronal ion homoeostasis during the propagation of action potentials. Interruption of mitochondrial function involves oxidative stress and leads to impaired energy production, followed by rapidly developing brain damage. For nearly three decades, ROS have been the focus of interest as possible candidates for the elicitation of deleterious responses in the pathogenesis of ischemia and TBI; however, despite numerous clinical trials, no antioxidants have made their way into clinical practice. This chapter focuses on the role of oxidative stress and tissue antioxidant capacity in the pathogenesis of TBI. Oxidative stress in the brain and its biological targets are discussed along with the tissue’s intrinsic defense mechanisms, including antioxidant enzymes and low molecular weight antioxidants (LMWA). Post-TBI oxidative stress-induced damage is described, highlighting its major hallmarks, namely mitochondrial damage, lipid peroxidation, antioxidant enzymes, and LMWA. Finally, several therapeutic agents harboring antioxidant properties are presented at the end of the chapter for their implications in both experimental and clinical settings.


Antioxidant enzymes Low molecular weight antioxidants Lipid peroxidation Mitochondria Oxidative stress 



This study was partially supported the Israel Science Foundation, (grant no. 241/04). E.S. and R.K. are affiliated with the David R. Bloom Center of Pharmacy and the Dr. Adolph and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics, of the Hebrew University, Jerusalem. E.S. is the incumbent of the Dr. Leon and Dr. Mina Deutsch Chair in Psychopharmacology, and R.K. is the incumbent of the Richard and Jean Zarbin Chair in Medical Studies, at the Hebrew University, Jerusalem.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of PharmacologyThe Hebrew University School of PharmacyJerusalemIsrael

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