{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:17:21Z","timestamp":1791443841537,"version":"4.3.3"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Phobic anxiety present after stroke (called poststroke anxiety, PSA) can hamper the rehabilitation of patients and disrupt their usual activities. Besides, the symptoms and mechanisms of PSA are different from those in nonstroke populations that have generalized anxiety disorder. What\u2019s more, the treatment approaches for phobic anxiety are confined to unitary or general methods with poor efficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Behavioural test screen combined bioinformatics analysis explored molecular changes between generalized anxiety disorder in nonstroke mice (restraint stress, RS) and photothrombotic stroke mice exposed to environmental stress (PTS + RS, mimicking PSA). Multiple molecular biological and neurobiological methods were employed to explain mechanisms <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. And exploiting gamma flicker stimulation device for therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microglial (MG) overactivation is a prominent characteristic of PTS + RS. HDAC3 was mainly upregulated in activated-microglia from damaged cortex and that local prostaglandin E2 (PGE<jats:sub>2<\/jats:sub>) production increased in MG <jats:italic>via<\/jats:italic> HDAC3-mediated activation of NF-\u03baB signalling by p65 deacetylation. A high content of PGE<jats:sub>2<\/jats:sub> in damaged ischaemic cortex could diffuse freely to amygdala, eliciting anxiety susceptibility of PSA <jats:italic>via<\/jats:italic> EP2. Importantly, gamma flicker stimulation relieved anxious behaviour of PTS + RS by modulating the HDAC3\/Cox1\/EP2 network at some extent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HDAC3-regulated PGE<jats:sub>2<\/jats:sub> production by microglia constitutes phobic anxiety susceptibility after stroke and a protective approach of gamma visual stimulation can be a candidate new therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.845678","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T14:35:40Z","timestamp":1645194940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["HDAC3-Regulated PGE2 Production by Microglia Induces Phobic Anxiety Susceptibility After Stroke and Pointedly Exploiting a Signal-Targeted Gamma Visual Stimulation New Therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Hongrui","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/1747493019896958","article-title":"Frequency of Anxiety After Stroke: An Updated Systematic Review and Meta-Analysis of Observational Studies","volume":"15","author":"Knapp","year":"2020","journal-title":"Int J Stroke"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.117.020078","article-title":"Anxiety After Stroke: The Importance of Subtyping","volume":"49","author":"Chun","year":"2018","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008860","article-title":"Interventions for Treating Anxiety After Stroke","volume":"5","author":"Knapp","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1590\/s2317-17822013000200017","article-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM)","volume":"25","author":"Battle","year":"2013","journal-title":"Codas"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1502514","article-title":"CLINICAL PRACTICE. 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