{"doi":"10.1101/2020.04.12.036392","title":"Microvascular Injury in Mild Traumatic Brain Injury Accelerates Alzheimer-like Pathogenesis in Mice","abstract":"Abstract Introduction Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer’s disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Methods We established a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, and examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also determined the brain clearance of β-amyloid, as well as amyloid pathology and cognitive functions after mTBI in the 5xFAD mouse model of AD. Results mTBI induced microvascular injury with BBB breakdown, pericyte loss and cerebral blood flow reduction in mice, which preceded gliosis. mTBI also impaired brain amyloid clearance via the vascular pathways. More importantly, mTBI accelerated amyloid pathology and cognitive impairment in the 5xFAD mice. Discussion Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126496,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9236,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":304615,"name":"Jianxiong Zeng","orcid":"0000-0002-7339-734X","position":1,"is_corresponding":false},{"id":303021,"name":"Brock Pluimer","orcid":null,"position":2,"is_corresponding":false},{"id":574373,"name":"Shirley Dong","orcid":null,"position":3,"is_corresponding":false},{"id":304617,"name":"Xiaochun Xie","orcid":"0000-0001-6826-9493","position":4,"is_corresponding":false},{"id":289054,"name":"Xinying Guo","orcid":"0000-0002-8428-5036","position":5,"is_corresponding":false},{"id":573968,"name":"Xinyan Liang","orcid":"0000-0003-3275-8548","position":6,"is_corresponding":false},{"id":574374,"name":"Sudi Feng","orcid":null,"position":7,"is_corresponding":false},{"id":300736,"name":"Haijian Wu","orcid":"0000-0003-1219-719X","position":8,"is_corresponding":false},{"id":306415,"name":"Youzhen Yan","orcid":null,"position":9,"is_corresponding":false},{"id":304625,"name":"Jian‐Fu Chen","orcid":"0000-0002-9474-5673","position":10,"is_corresponding":false},{"id":573969,"name":"Naomi S. Sta Maria","orcid":"0000-0001-9710-2908","position":11,"is_corresponding":false},{"id":496373,"name":"Qingyi Ma","orcid":"0000-0002-3499-0992","position":12,"is_corresponding":false},{"id":472618,"name":"Fernando Gómez‐Pinilla","orcid":null,"position":13,"is_corresponding":false},{"id":294874,"name":"Zhen Zhao","orcid":"0000-0001-8967-5570","position":14,"is_corresponding":false},{"id":303020,"name":"Yingxi Wu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","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":[]}