{"doi":"10.1101/2022.09.23.509276","title":"Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model","abstract":"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 the development of therapies for TBI patients.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301905,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":894355,"name":"Nicholas J. Fiore","orcid":"0000-0002-8052-0588","position":1,"is_corresponding":false},{"id":993388,"name":"Yang Zhang","orcid":"0009-0003-0244-8036","position":2,"is_corresponding":false},{"id":109092,"name":"Yuka Milton","orcid":"0000-0001-5362-3015","position":3,"is_corresponding":false},{"id":993886,"name":"Marilyn Kelly","orcid":null,"position":4,"is_corresponding":false},{"id":993389,"name":"Marly Coe","orcid":"0000-0003-1920-8154","position":5,"is_corresponding":false},{"id":993887,"name":"Ariana Barreiro","orcid":null,"position":6,"is_corresponding":false},{"id":993888,"name":"Victoria K. Rose","orcid":null,"position":7,"is_corresponding":false},{"id":993889,"name":"Matthew R. Shapiro","orcid":null,"position":8,"is_corresponding":false},{"id":957866,"name":"Adam S. Mullis","orcid":"0000-0002-5186-5093","position":9,"is_corresponding":false},{"id":958281,"name":"Anna Shevzov-Zebrun","orcid":null,"position":10,"is_corresponding":false},{"id":7841,"name":"Mathew Blurton-Jones","orcid":"0000-0002-7770-7157","position":11,"is_corresponding":false},{"id":437823,"name":"Michael J. Whalen","orcid":"0000-0001-8208-5981","position":12,"is_corresponding":false},{"id":988643,"name":"Aviva J. Symes","orcid":"0000-0003-2557-9939","position":13,"is_corresponding":false},{"id":308841,"name":"Irene Georgakoudi","orcid":"0000-0002-0049-6697","position":14,"is_corresponding":false},{"id":294774,"name":"Thomas J.F. Nieland","orcid":"0000-0003-1255-2104","position":15,"is_corresponding":false},{"id":225373,"name":"David L. Kaplan","orcid":"0000-0002-9245-7774","position":16,"is_corresponding":false},{"id":327319,"name":"Volha Liaudanskaya","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}