{"doi":"10.3389/fstro.2024.1423887","title":"Astroglial CD38 impairs hippocampal synaptic plasticity after global cerebral ischemia","abstract":"Cardiac arrest-induced global cerebral ischemia (GCI) results in profound cognitive impairment in survivors. Our prior work demonstrated persistent disruption of long-term potentiation (LTP) in hippocampal CA1 neurons, correlating with learning and memory deficits in a rodent model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Delayed inhibition of the Ca 2+ -permeable TRPM2 ion channel restored LTP post-CA/CPR, yet the mechanisms upstream of TRPM2 activation remain elusive. This study investigates CD38 as a potential regulator of TRPM2, highlighting a novel target to reverse hippocampal synaptic plasticity deficits after ischemia. We observe elevated levels of CD38 in activated astrocytes in the CA1 region of the hippocampus 7 days following CA/CPR in both male and female mice. Delayed inhibition of CD38 reverses hippocampal synaptic plasticity impairments at subacute timepoints after CA/CPR, phenocopying TRPM2 restoration of LTP. Our previous findings demonstrated that TRPM2 inhibition reverses the CA/CPR-induced enhancement of GABA A receptor (GABA A R) clustering, which contribute to ongoing LTP deficits. We, therefore, assessed the effect of CD38 on GABAergic inhibitory potentiation and find that inhibition of CD38 reverses GABA A R clustering in a TRPM2-dependent manner. In this study, we identify astroglial CD38 as a potential target and upstream regulator of the TRPM2 channel, offering a promising approach to restore hippocampal synaptic plasticity impairments following GCI through modulation of GABAergic signaling.","journal":"Frontiers in Stroke","year":2024,"id":452290,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":723278,"name":"Ami Haas","orcid":"0000-0001-9815-8954","position":1,"is_corresponding":false},{"id":406256,"name":"James E. Orfila","orcid":"0000-0003-1052-9795","position":2,"is_corresponding":false},{"id":688710,"name":"Erika Tiemeier","orcid":null,"position":3,"is_corresponding":false},{"id":1274516,"name":"Cassidy De Anda Gamboa","orcid":null,"position":4,"is_corresponding":false},{"id":345712,"name":"Nicholas Chalmers","orcid":"0009-0004-0778-6840","position":5,"is_corresponding":false},{"id":345716,"name":"Nidia Quillinan","orcid":"0000-0002-5708-8395","position":6,"is_corresponding":false},{"id":345717,"name":"Paco S. Herson","orcid":"0000-0002-3590-8751","position":7,"is_corresponding":false},{"id":624111,"name":"Amelia Burch","orcid":"0000-0001-8533-4293","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:02:50.407779Z","pmid":"40822706","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":[]}