Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 03, 2023
- Source ID
- 10.1038/s41419-023-05980-0
Entities
People
- Adam S Mullis
- Anna Shevzov-zebrun
- Ariana Barreiro
- Aviva J Symes
- David L. Kaplan
- Irene Georgakoudi
- Marilyn F. Kelly
- Marly Coe
- Mathew Blurton-Jones
- Matthew R. Shapiro
- Michael J. Whalen
- Nicholas J. Fiore
- Thomas J. F. Nieland
- Victoria K. Rose
- Volha Liaudanskaya
- Yang Zhang
- Yuka Milton
Organizations
- National Institute of Biomedical Imaging and Bioengineering
- National Institute on Aging
- National Institutes of Health
- United States Department of Defense