{"doi":"10.1016/j.ibneur.2020.11.003","title":"Intracisternal administration of tanshinone IIA-loaded nanoparticles leads to reduced tissue injury and functional deficits in a porcine model of ischemic stroke","abstract":"The absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model. Tan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm3) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (−37.30 ± 3.67 vs. −46.33 ± 0.73%) and white matter integrity (−19.66 ± 5.58 vs. −30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm3) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs. The findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients.","journal":"IBRO Neuroscience Reports","year":2021,"id":180049,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":352681,"name":"Erin E. Kaiser","orcid":"0000-0003-1521-950X","position":1,"is_corresponding":false},{"id":603228,"name":"Xueyuan Yang","orcid":"0000-0002-1519-6830","position":2,"is_corresponding":false},{"id":493679,"name":"Madison M. Fagan","orcid":"0000-0003-1084-6547","position":3,"is_corresponding":false},{"id":352683,"name":"Kelly M. Scheulin","orcid":"0000-0002-3580-6229","position":4,"is_corresponding":false},{"id":352679,"name":"Julie Jeon","orcid":"0000-0002-6862-144X","position":5,"is_corresponding":false},{"id":494686,"name":"Soo K. Shin","orcid":null,"position":6,"is_corresponding":false},{"id":352685,"name":"Holly A. Kinder","orcid":"0000-0001-8310-7265","position":7,"is_corresponding":false},{"id":529089,"name":"Anil Kumar","orcid":"0000-0002-9979-7798","position":8,"is_corresponding":false},{"id":352686,"name":"Simon R. Platt","orcid":"0000-0002-7818-1011","position":9,"is_corresponding":false},{"id":494687,"name":"Kylee J. Duberstein","orcid":null,"position":10,"is_corresponding":false},{"id":352690,"name":"Hea Jin Park","orcid":"0000-0002-1611-1077","position":11,"is_corresponding":false},{"id":352634,"name":"Jin Xie","orcid":"0000-0002-8915-6233","position":12,"is_corresponding":false},{"id":352689,"name":"Franklin D. West","orcid":"0000-0002-0504-7997","position":13,"is_corresponding":false},{"id":352682,"name":"Elizabeth S. Waters","orcid":"0000-0002-6106-0360","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:47:53.089578Z","pmid":"33842909","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":[]}