Transplantation of Astrocytic Mitochondria for Intracerebral Hemorrhage Treatment

Transplantation of Astrocytic Mitochondria for Intracerebral Hemorrhage Treatment

Level of Mn-SOD in neurons 21 days after hemmorage in mice that received mitochondria with and without Mn-SOD at one hour, seven days, and 14 days post-hemmorage. White arrows indicate the cells showing high Mn-SOD (red) in the neurons as a result of the treatment. 

News Release, World Mitochondria Society, Berlin - Germany – August 17, 2022

Astrocytes release functional mitochondria that play regulatory and pro-survival functions upon entering adjacent cells. These released mitochondria can enter microglia and promote their reparative/pro-phagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage. 

The robust increase in superoxide generation and elevated oxidative damage during intracerebral hemorrhage coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). Tahiro et al. showed that intravenous transplantation of astrocytic mitochondria reversed the damaging effect of intracerebral hemorrhage. 

When the astrocytic mitochondria entered the brain (and neurons) they restored Mn-SOD levels and reduced neurological deficits in male mice subjected to intracerebral hemorrhage. Astrocytic mitochondria prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels, while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. The mitochondria genome-encoded small peptide humanin could simulate mitochondria-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under intracerebral hemorrhage-like injury.

In summary, adoptive astrocytic mitochondrial transfer enhances neuronal Mn-SOD-mediated anti-oxidative defense and neuroplasticity in the brain, which potentiate functional recovery following intracerebral hemorrhage.

Paper DOI.

© Image -Tashiro et al., JNeurosci 2022

Targeting Mitochondria 2022 will dedicate a whole session for Mitochondrial transplantation and transfer. Conference Program.


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