Exploring the Mechanism and Therapeutic Potential of Mitochondrial Transplantation (MT) Using Astrocytic Extracellular Vesicles Containing Mitochondria (mtEV) in Traumatic Brain Injury

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Description

Traumatic brain injury (TBI) leads to neuronal damage, neurodegeneration, and cognitive deficits, as evidenced by over 220,000 hospitalizations and 64,000 deaths in 2020 alone. Despite the prevalence of TBI, no FDA-approved treatments exist. Mitochondrial dysfunction, a hallmark of various diseases, is increasingly linked to TBI-related neuropathology. Mitochondria are highly dynamic organelles and protecting or restoring mitochondrial function improves neuronal function after TBI. While horizontal mitochondrial transfer (HMT) and exogenous mitochondrial transplantation (EMT) show promise in mitigating mitochondrial dysfunction, robust in vivo evidence is limited, particularly regarding the fate and functionality of transplanted mitochondria in the brain. This study aims to bridge these knowledge gaps by exploring mitochondrial transfer mechanisms under both physiological and pathological conditions. Utilizing a tamoxifen-inducible mouse model expressing green-fluorescent dendra-2 (mtD2) specifically in astrocyte mitochondria (Aldh1l1-CreER; mtD2f/f (Ast-mtD2)), we have demonstrated HMT from astrocytes to neurons under basal conditions. Post-TBI, rapid morphological changes in astrocytic mitochondria were detected in the penumbral region but it is not known how this relates to astrocytic mitochondrial function or bioenergetics. This research aims to uncover novel therapeutic strategies for TBI by leveraging mitochondrial transfer and transplantation techniques, potentially paving the way for new treatments targeting mitochondrial dysfunction in neurodegenerative conditions.
StatusActive
Effective start/end date2/1/251/31/28

Funding

  • KY Spinal Cord and Head Injury Research Trust: $99,997.00

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