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.
Abbreviation:
ATP (Adenosine triphosphate), BDNF (Brain-derived neurotrophic factor), BSA (Bovine serum albumin), CCI (Controlled cortical impact), EM (Electron microscope), GFAP (Glial fibrillary acidic protein), JNK (Jun N-terminal Kinase), PBS (Phosphate buffered saline), PCR (Polymerase chain reaction), PFA (Paraformaldehyde), ROS (Reactive oxygen species), TBI (Traumatic brain injury)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Rehabilitation Treatment and Progress of Traumatic Brain Injury Dysfunction.Neural plasticity. 2017; 20171582182
- Current Perspectives in the Surgical Treatment of Severe Traumatic Brain Injury.World neurosurgery. 2018; 116: 322-328
- Management of Traumatic Brain Injury: From Present to Future.Antioxidants-Basel. 2020; 9https://doi.org/10.3390/antiox9040297
- The contribution of astrocytes and microglia to traumatic brain injury.British journal of pharmacology. 2016; 173: 692-702
- Cell Death and Recovery in Traumatic Brain Injury.Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. 2020; 17: 446-456
- Astrocytes: biology and pathology.Acta neuropathologica. 2010; 119: 7-35
- Astrocyte roles in traumatic brain injury.Experimental neurology. 2016; 275: 305-315
- Mitochondria Know No Boundaries: Mechanisms and Functions of Intercellular Mitochondrial Transfer.Front Cell Dev Biol. 2016; 4https://doi.org/10.3389/fcell.2016.00107
- Intercellular mitochondrial transfer: bioenergetic crosstalk between cells.Curr Opin Genet Dev. 2016; 38: 97-101
- Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress.Blood. 2019; 134: 1415-1429
- Transfer of mitochondria from astrocytes to neurons after stroke.Nature. 2016; 535: 551-555
- Mitochondrial Transfer from Bone Marrow Mesenchymal Stem Cells to Motor Neurons in Spinal Cord Injury Rats via Gap Junction.Theranostics. 2019; 9: 2017-2035
- Mesenchymal stem cells transfer mitochondria into cerebral microvasculature and promote recovery from ischemic stroke.Microvasc Res. 2019; 123: 74-80
- Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury.American journal of physiology Heart and circulatory physiology. 2013; 304: H966-H982
- Actin and myosin contribute to mammalian mitochondrial DNA maintenance.Nucleic acids research. 2011; 39: 5098-5108
- Characterization of an improved procedure for the removal of microglia from confluent monolayers of primary astrocytes.Journal of neuroscience methods. 2006; 150: 128-137
- Optimized protocols for isolation of primary motor neurons, astrocytes and microglia from embryonic mouse spinal cord.Journal of neuroscience methods. 2007; 163: 111-118
- Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress.International journal of clinical and experimental medicine. 2015; 8: 5103-5111
- Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury.J Thorac Cardiov Sur. 2017; 154: 286-289
- BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease.Gene Ther. 2010; 17: 1294-1308
- Truncated TrkB.T1-Mediated Astrocyte Dysfunction Contributes to Impaired Motor Function and Neuropathic Pain after Spinal Cord Injury.Journal of Neuroscience. 2017; 37: 3956-3971
- Mitochondrial transplantation as a potential and novel master key for treatment of various incurable diseases.Cytotechnology. 2019; 71: 647-663
- Endocytosis-mediated mitochondrial transplantation: Transferring normal human astrocytic mitochondria into glioma cells rescues aerobic respiration and enhances radiosensitivity.Theranostics. 2019; 9: 3595-3607
- Allogeneic/xenogeneic transplantation of peptide-labeled mitochondria in Parkinson's disease: restoration of mitochondria functions and attenuation of 6-hydroxydopamine-induced neurotoxicity.Transl Res. 2016; 170: 40-56
- Mitochondrial DNA in innate immune responses and inflammatory pathology.Nat Rev Immunol. 2017; 17: 363-375
- JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells.Biochemical pharmacology. 2020; 171: 113728
- Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis.Cell research. 2018; 28: 1171-1185
- Questions and (some) answers on reactive astrocytes.Glia. 2019; 67: 2221-2247
- Ground control to major TOM: mitochondria-nucleus communication.Febs Journal. 2017; 284: 196-210
- Mitonuclear communication in homeostasis and stress.Nat Rev Mol Cell Bio. 2016; 17: 213-226
- Mitochondrial Transplantation Attenuates Brain Dysfunction in Sepsis by Driving Microglial M2 Polarization.Molecular neurobiology. 2020; 57: 3875-3890
Article info
Publication history
Published online: March 30, 2021
Accepted:
March 23,
2021
Received in revised form:
February 21,
2021
Received:
October 23,
2020
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
