Grants and Contracts Details
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.
Status | Active |
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Effective start/end date | 2/1/25 → 1/31/28 |
Funding
- KY Spinal Cord and Head Injury Research Trust: $99,997.00
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