Mitochondria transplantation protects traumatic brain injury via promoting neuronal survival and astrocytic BDNF

Transl Res. 2021 Sep:235:102-114. doi: 10.1016/j.trsl.2021.03.017. Epub 2021 Mar 30.

Abstract

Traumatic brain injury (TBI) is one of the leading causes of disability and paralysis around the world. Secondary injury, characterized by progressive neuronal loss and astrogliosis, plays important roles in the post-TBI cognitive impairment and mood disorder. Unfortunately, there still lacks effective treatments, particularly surgery interferences for it. Recent findings of intercellular mitochondria transfer implies a potential therapeutic value of mitochondria transplantation for TBI, which has not been tested yet. In the present study, we demonstrated a quick dysfunction of mitochondria, up-regulation of Tom20 in the injured cortex and subsequent cognitive and mood impairment. Our data demonstrated that mitochondria derived from allogeneic liver or autogeneic muscle stimulated similar microglial activation in brain parenchyma. In vitro experiments showed that exogenous mitochondria could be easily internalized by neurons, astrocytes, and microglia, except for oligodendrocytes. Mitochondria transplantation effectively rescued neuronal apoptosis, restored the expression of Tom20 and the phosphorylation of JNK. Further analysis revealed that mitochondria transplantation in injured cortex induced a significant up-regulation of BDNF in reactive astrocytes, improved animals' spatial memory and alleviated anxiety. In together, our data indicate that mitochondria transplantation may has the potential of clinical translation for TBI treatment, in combination with surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Brain Injuries, Traumatic / physiopathology
  • Brain Injuries, Traumatic / psychology
  • Brain Injuries, Traumatic / therapy*
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • Cell Survival
  • Cells, Cultured
  • Endocytosis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / physiology
  • Mitochondria / transplantation*
  • Neurons / physiology*

Substances

  • Brain-Derived Neurotrophic Factor