{"doi":"10.1101/2023.04.02.535245","title":"Neuronal and Astrocyte Insulin-like Growth Factor-1 Signaling Differentially Modulates Ischemic Stroke Damage","abstract":"Ischemic stroke is a leading cause of death and disability, as therapeutic options for mitigating the long-term deficits precipitated by the event remain limited. Acute administration of the neuroendocrine modulator insulin-like growth factor-1 (IGF-1) attenuates ischemic stroke damage in preclinical models, and clinical studies suggest IGF-1 can reduce the risk of stroke and improve overall outcomes. The cellular mechanism by which IGF-1 exerts this protection is poorly defined, as all cells within the neurovascular unit express the IGF-1 receptor. We hypothesize that the functional regulation of both neurons and astrocytes by IGF-1 is critical in minimizing damage in ischemic stroke. To test this, we utilized inducible astrocyte-specific or neuron-specific transgenic mouse models to selectively reduce IGF-1R in the adult mouse brain prior to photothrombotic stroke. Acute changes in blood brain barrier permeability, microglial activation, systemic inflammation, and biochemical composition of the brain were assessed 3 hours following photothrombosis, and significant protection was observed in mice deficient in neuronal and astrocytic IGF-1R. When the extent of tissue damage and sensorimotor dysfunction was assessed for 3 days following stroke, only the neurological deficit score continued to show improvements, and the extent of improvement was enhanced with additional IGF-1 supplementation. Overall, results indicate that neuronal and astrocytic IGF-1 signaling influences stroke damage but IGF-1 signaling within these individual cell types is not required for minimizing tissue damage or behavioral outcome.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392281,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1165867,"name":"Nyah I. Morgan","orcid":null,"position":1,"is_corresponding":false},{"id":904418,"name":"Kamryn C. Thomas","orcid":null,"position":2,"is_corresponding":false},{"id":353115,"name":"M. Jake Pushie","orcid":"0000-0001-7494-5427","position":3,"is_corresponding":false},{"id":750606,"name":"Akshaya Vijayasankar","orcid":null,"position":4,"is_corresponding":false},{"id":750605,"name":"Brandon G. Ashmore","orcid":null,"position":5,"is_corresponding":false},{"id":860785,"name":"Kendall Wontor","orcid":"0000-0002-2045-3782","position":6,"is_corresponding":false},{"id":1165868,"name":"Miguel A. De Leon","orcid":null,"position":7,"is_corresponding":false},{"id":413389,"name":"Nicole M. Ashpole","orcid":"0000-0002-0696-2599","position":8,"is_corresponding":false},{"id":750012,"name":"Cellas A. Hayes","orcid":"0000-0002-6259-9456","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:18:52.232318Z","pmid":"37034764","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":[]}