{"doi":"10.1101/2025.05.01.651070","title":"Microglia modulate concussion biomarkers and cognitive recovery in male mice","abstract":"Microglial state at the time of concussion dictates cognitive outcomes, yet the underlying mechanisms remain unclear, and non-invasive tools to predict recovery trajectories remain elusive. Here, we tested whether microglia are causally required for concussion-induced deficits and the neuroprotection conferred by subconcussive preconditioning. Using PLX5622 to deplete microglia in a preclinical model, we observed opposing cognitive effects: depletion rescues deficits from concussion alone but eliminates preconditioning-induced protection. To characterize the molecular mechanisms underlying these divergent trajectories, we performed single-nuclei transcriptomics and isolated brain-derived (GluR1/2+) extracellular vesicles (EVs) from plasma. We found that microglial presence and subconcussive preconditioning fundamentally alter injury biomarkers and signaling pathways across multiple cell types. Furthermore, we identified a plasma EV miRNA panel that predicts cognitive recovery across varied injury conditions. Together, these results demonstrate a dual, context-dependent role for microglia in concussion outcomes and establish brain-derived EVs as a powerful tool for surveilling neuroinflammatory processes governing recovery. Teaser: Microglial state during concussion affects cognitive recovery and neuron-enriched extracellular vesicle biomarkers.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556249,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1455963,"name":"Daunel V Augustin","orcid":null,"position":1,"is_corresponding":false},{"id":1455551,"name":"Anastasia P Georges","orcid":"0000-0001-6340-8327","position":2,"is_corresponding":false},{"id":1059570,"name":"T. Kim","orcid":"0009-0004-1788-3820","position":3,"is_corresponding":false},{"id":247315,"name":"David Issadore","orcid":"0000-0002-5461-8653","position":4,"is_corresponding":false},{"id":345520,"name":"David F. Meaney","orcid":"0000-0002-0954-4122","position":5,"is_corresponding":false},{"id":930660,"name":"Erin D. Anderson","orcid":"0000-0003-0575-6707","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:08.896385Z","pmid":"42239156","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":[]}