{"doi":"10.1101/2020.10.15.339184","title":"Neuroprotective pentapeptide, CN-105, improves outcomes in translational models of intracerebral hemorrhage","abstract":"Abstract Background Intracerebral hemorrhage (ICH) is a devastating form of cerebrovascular disease for which there are no approved pharmacological interventions that improve outcomes. Apolipoprotein E (apoE) has emerged as a promising therapeutic target given its neuroprotective properties and ability to modify neuroinflammatory responses. We developed a 5-amino acid peptide, CN-105, that mimics the polar face of the apoE helical domain involved in receptor interactions, readily crosses the blood-brain barrier, and improves outcomes in well-established preclinical ICH models. In the current study, we investigated the therapeutic potential of CN-105 in translational ICH models that account for hypertensive comorbidity, sex, species, and age. Methods In three separate experiments, we delivered three intravenous doses of CN-105 (up to 0.20 mg/kg) or vehicle to hypertensive male BPH/2J mice, spontaneously hypertensive female rats, or 11-month old male mice within 24-hours of ICH. Neuropathological and neurobehavioral outcomes were determined over 3, 7, and 9 days, respectively. Results In spontaneously hypertensive male mice, there was a significant dose-dependent effect of CN-105 on vestibulomotor function at 0.05 and 0.20 mg/kg doses (p < 0.05; 95% CI: 0.91 – 153.70 and p < 0.001; 95% CI: 49.54 – 205.62), while 0.20 mg/kg also improved neuroseverity scores (p < 0.05; 95% CI: 0.27 – 11.00) and reduced ipsilateral brain edema (p < 0.05; 95% CI: − 0.037 – − 0.001). In spontaneously hypertensive female rats, CN-105 (0.05 mg/kg) had a significant effect on vestibulomotor function (p < 0.01; η 2 = 0.093) and neuroseverity scores (p < 0.05; η 2 = 0.083), and reduced contralateral edema expansion (p < 0.01; 95% CI: − 1.41 – − 0.39). In 11-month old male mice, CN-105 had a significant effect on vestibulomotor function (p < 0.001; η 2 = 0.111) but not neuroseverity scores (p > 0.05; η 2 = 0.034). Conclusions Acute treatment with CN-105 improves outcomes in translational ICH models independent of sex, species, age, or hypertensive comorbidity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124127,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"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":568416,"name":"Timothy D. Faw","orcid":"0000-0001-7794-0074","position":1,"is_corresponding":false},{"id":568417,"name":"Yufeng Lin","orcid":"0000-0001-5705-0787","position":2,"is_corresponding":false},{"id":284820,"name":"Shan Huang","orcid":"0000-0001-8492-9658","position":3,"is_corresponding":false},{"id":568418,"name":"Talaignair N. Venkatraman","orcid":"0000-0002-8565-7604","position":4,"is_corresponding":false},{"id":366374,"name":"Viviana Cantillana","orcid":"0000-0002-1962-1013","position":5,"is_corresponding":false},{"id":568419,"name":"Christopher D. Lascola","orcid":"0000-0002-8031-782X","position":6,"is_corresponding":false},{"id":568420,"name":"Michael L. James","orcid":"0000-0002-8715-5210","position":7,"is_corresponding":false},{"id":568421,"name":"Daniel T. Laskowitz","orcid":"0000-0003-3430-8815","position":8,"is_corresponding":false},{"id":320917,"name":"Haichen Wang","orcid":"0000-0001-5244-6694","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","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":[]}