- Liaudanskaya, Volha;
- Fiore, Nicholas;
- Zhang, Yang;
- Milton, Yuka;
- Kelly, Marilyn;
- Coe, Marly;
- Barreiro, Ariana;
- Rose, Victoria;
- Shapiro, Matthew;
- Mullis, Adam;
- Shevzov-Zebrun, Anna;
- Whalen, Michael;
- Symes, Aviva;
- Georgakoudi, Irene;
- Nieland, Thomas;
- Kaplan, David;
- Blurton-Jones, Mathew
Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients.