Mitochondrial Dysfunction in Nervous System Injury

D. A. Butterfield, W. O. Opii

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

2 Scopus citations


Mitochondria are involved in energy metabolism, regulation of Ca2+, regulation of cell survival or cell death, production and detoxification of reactive oxygen species, among many other functions. Injury to the nervous system is mediated to a significant extent by the mitochondria. This involves an initial rapid necrotic event to neuronal tissue at the site of injury, followed by a progressive secondary injury that results in significant neuronal damage. Following central nervous system (CNS) injury, excitotoxicity occurs, leading to a massive influx of Ca2+ resulting in alterations of Ca2+ homeostasis and increased production of reactive oxygen or nitrogen species. The Ca2+ overload leads to the induction of a mitochondrial permeability transition, resulting in the opening of the mitochondria permeability transition pore. This then leads to the depolarization of the mitochondrial membrane potential, decline in ATP synthesis, swelling of the mitochondria, and the eventual release of pro-apoptotic factors, such as cytochrome c and apoptosis-inducing factor, from the inner mitochondrial membrane. This, in turn, results in the initiation of the caspase-mediated cell death pathways. Maintenance of neuronal mitochondrial homeostasis and bioenergetics following injury becomes a critical event mediated by endogenous antioxidant systems. However, during nervous system injury, these protective mechanisms are usually overwhelmed. This article focuses on the role of the mitochondria in CNS injury, specifically in traumatic brain injury, spinal cord injury, and stroke/cerebral ischemia.

Original languageEnglish
Title of host publicationEncyclopedia of Neuroscience
Number of pages8
StatePublished - 2009


  • Antioxidants
  • Apoptosis
  • Central nervous system
  • Energy metabolism
  • Excitotoxicity
  • Injury
  • Mitochondria
  • Necrosis
  • Neurons
  • Oxidative stress

ASJC Scopus subject areas

  • General Neuroscience


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