{"doi":"10.14336/ad.2019.0507","title":"Neuropsychological Deficits Chronically Developed after Focal Ischemic Stroke and Beneficial Effects of Pharmacological Hypothermia in the Mouse","abstract":"Stroke is a leading cause of human death and disability, with around 30% of stroke patients develop neuropsychological/neuropsychiatric symptoms, such as post-stroke depression (PSD). Basic and translational research on post-stroke psychological disorders is limited. In a focal ischemic stroke mouse model with selective damage to the sensorimotor cortex, sensorimotor deficits develop soon after stroke and spontaneous recovery is observed in 2-4 weeks. We identified that mice subjected to a focal ischemic insult gradually developed depression/anxiety like behaviors 4 to 8 weeks after stroke. Psychological/psychiatric disorders were revealed in multiple behavioral examinations, including the forced swim, tail suspension, sucrose preference, and open field tests. Altered neuronal plasticity such as suppressed long-term potentiation (LTP), reduced BDNF and oxytocin signaling, and disturbed dopamine synthesis/uptake were detected in the prefrontal cortex (PFC) during the chronic phase after stroke. Pharmacological hypothermia induced by the neurotensin receptor 1 (NTR1) agonist HPI-363 was applied as an acute treatment after stroke. A six-hr hypothermia treatment applied 45 min after stroke prevented depression and anxiety like behaviors examined at 6 weeks after stroke, as well as restored BDNF expression and oxytocin signaling. Additionally, hypothermia induced by physical cooling also showed an anti-depression and anti-anxiety effect. The data suggested a delayed beneficial effect of acute hypothermia treatment on chronically developed post-stroke neuropsychological disorders, associated with regulation of synaptic plasticity, neurotrophic factors, dopaminergic activity, and oxytocin signaling in the PFC.","journal":"Aging and Disease","year":2020,"id":96912,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"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":480276,"name":"Yuan Yan","orcid":"0009-0004-6106-6908","position":1,"is_corresponding":false},{"id":480277,"name":"Gu Xiaohuan","orcid":null,"position":2,"is_corresponding":false},{"id":480278,"name":"Kim Samuel In-young","orcid":null,"position":3,"is_corresponding":false},{"id":480279,"name":"Chin Ryan","orcid":null,"position":4,"is_corresponding":false},{"id":480280,"name":"Loye Modupe","orcid":null,"position":5,"is_corresponding":false},{"id":480281,"name":"Dix Thomas A","orcid":null,"position":6,"is_corresponding":false},{"id":355145,"name":"Ling Wei","orcid":"0000-0002-4003-2109","position":7,"is_corresponding":false},{"id":480282,"name":"Yu Shan Ping","orcid":null,"position":8,"is_corresponding":false},{"id":480275,"name":"Zhong Weiwei","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T22:35:06.014648Z","pmid":"32010477","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":[]}