Rescuing mitochondria in traumatic brain injury and intracerebral hemorrhages - A potential therapeutic approach

Neurochem Int. 2021 Nov;150:105192. doi: 10.1016/j.neuint.2021.105192. Epub 2021 Sep 22.


Mitochondria are dynamic organelles responsible for cellular energy production. Besides, regulating energy homeostasis, mitochondria are responsible for calcium homeostasis, signal transmission, and the fate of cellular survival in case of injury and pathologies. Accumulating reports have suggested multiple roles of mitochondria in neuropathologies, neurodegeneration, and immune activation under physiological and pathological conditions. Mitochondrial dysfunction, which occurs at the initial phase of brain injury, involves oxidative stress, inflammation, deficits in mitochondrial bioenergetics, biogenesis, transport, and autophagy. Thus, development of targeted therapeutics to protect mitochondria may improve functional outcomes following traumatic brain injury (TBI) and intracerebral hemorrhages (ICH). In this review, we summarize mitochondrial dysfunction related to TBI and ICH, including the mechanisms involved, and discuss therapeutic approaches with special emphasis on past and current clinical trials.

Keywords: Brain injury; Immune activation; Mitochondrial bioenergetics; Mitochondrial biogenesis; Mitophagy; Therapeutic approach.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / physiology
  • Brain Injuries, Traumatic / drug therapy
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology
  • Cerebral Hemorrhage / drug therapy
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitophagy / drug effects
  • Mitophagy / physiology*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology


  • Free Radical Scavengers
  • Hypoglycemic Agents
  • Neuroprotective Agents