{"doi":"10.33915/etd.12822","title":"Mechanisms of neurovascular dysfunction in chronic ischemic stroke: insights from sex and aging","abstract":"Ischemic stroke is the leading cause of long-term disability world-wide. These disabilities can include both cognitive impairment and sensorimotor deficits. Due to the prevalence of post-stroke functional deficits, it is imperative to identify novel therapeutic targets and develop new treatments. These cognitive deficits are a result of damage to the neurovascular unit (NVU), a term used to describe the relationship between the cerebral vasculature and other cell types within the brain. Cognitive impairment as a result of damage to the NVU is referred to as vascular contributions to cognitive impairment and dementia (VCID), and it is estimated that between 25-30% of ischemic stroke survivors will develop some degree of VCID. While VCID can develop quickly following a stroke, some patients experience the onset several years after the initial stroke. Neuropathology, such as neuroinflammation, cerebral microhemorrhages, microinfarcts, cerebral edema, and white matter damage, can be utilized to determine the level of risk of developing VCID. While the primary risk factor of developing VCID is an ischemic stroke, other risk factors such as cardiovascular dysfunction, age, and biological sex can increase the risk of developing VCID post-stroke. In chapter 2, I investigated how pre-existing neurological disease (Alzheimer’s disease [AD]) can impact post- stroke neuropathology leading to VCID. In this study, I found an increase in AD-like pathology post-stroke in addition to increased neuropathology known to lead to VCID, such as microhemorrhaging, cerebral edema, and white matter damage. This shows that the presence of AD-like pathology leads to an increased risk of developing VCID post-stroke. In chapter 3, I investigated the potential role of endothelial cell (EC) tissue-nonspecific alkaline phosphatase (TNAP) in maintaining the NVU post-stroke. In this study, I found that the loss of EC TNAP resulted in an increased risk of developing neuropathology leading to VCID, such as increased neuroinflammation, cerebral edema, microhemorrhaging, and white matter damage. This shows that the loss of EC TNAP can result in an increased risk of developing VCID post-stroke. In chapter 4, I investigated advanced age as a factor for developing VCID. In this study, I found that with advanced age, there is less of an effect of EC TNAP in the preservation of the NVU, likely due to age-related confounds. This emphasizes the need for stroke studies to occur in an aged population, as this is the population most vulnerable to strokes. Throughout chapters 2, 3, and 4, I investigated the impact of biological","journal":"The Research Repository @ WVU (West Virginia University)","year":2025,"id":567078,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":1299495,"name":"Briana L Clary","orcid":"0000-0002-1839-0540","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:56:40.491968Z","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":[]}