Diffuse axonal injury and oxidative stress: A comprehensive review

Alessandro Frati, Daniela Cerretani, Anna Ida Fiaschi, Paola Frati, Vittorio Gatto, Raffaele La Russa, Alessandro Pesce, Enrica Pinchi, Alessandro Santurro, Flavia Fraschetti, Vittorio Fineschi

Research output: Contribution to journalReview articlepeer-review

Abstract

Traumatic brain injury (TBI) is one of the world’s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

Original languageEnglish
Article number2600
JournalInternational Journal of Molecular Sciences
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2 2017

Keywords

  • Biomarkers
  • Immunohistochemistry
  • Oxidative stress
  • Reactive oxygen species
  • Traumatic brain injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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