{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:58:24Z","timestamp":1792119504510,"version":"4.4.0"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2017\/27\/B\/NZ3\/00582"],"award-info":[{"award-number":["2017\/27\/B\/NZ3\/00582"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microglia play a key role in the development of neuroinflammation induced by cerebral ischemia. On the other hand, these cells participate in neurorepair processes. This dual role of microglia stems from the ability to shift their phenotype from pro-inflammatory M1 to protective M2. Histone deacetylase inhibitors (HDACis) are a group of agents that exhibit neuroprotective effects in some models of ischemia, among others, by modulation of signaling pathways that regulate microglial activation. This study aimed to examine the effect of HDACis\u2014sodium butyrate and Givinostat\u2014on polarization of microglia and their potential mechanism of action in a model of ischemia in vitro (oxygen and glucose deprivation, OGD). We examined the expression of pro- and anti-inflammatory markers in the BV2 microglial cell line after OGD and HDACis treatment by qPCR; polarization of microglia by flow cytometry; and the activation\/phosphorylation of ERK and AKT in BV2 cells by Western blot and ELISA. Our findings demonstrate a divergent impact of HDACis on the phenotype of microglial cells. Sodium butyrate significantly suppressed the mRNA expression of pro-inflammatory markers (IL-1\u03b2, TNF-\u03b1, CD86) and increased the level of anti-inflammatory factors in BV2 microglial cells after OGD, whereas Givinostat failed to attenuate these inflammatory responses. Our findings demonstrate that sodium butyrate, but not Givinostat, promotes a shift in microglia toward an anti-inflammatory M2 phenotype under ischemic conditions. This effect is associated with suppression of pro-inflammatory gene expression and activation of the PI3K\/AKT signaling pathway. These results identify sodium butyrate as a potential modulator of microglial responses following ischemic injury.<\/jats:p>","DOI":"10.3390\/ijms27021114","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Diverse Effect of HDAC Inhibitors: Sodium Butyrate and Givinostat on Microglia Polarization After Hypoxia-Ischemia In Vitro"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4265-4497","authenticated-orcid":false,"given":"Karolina","family":"Ziabska","sequence":"first","affiliation":[{"name":"NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Pawelec","sequence":"additional","affiliation":[{"name":"NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3205-5949","authenticated-orcid":false,"given":"Luiza","family":"Stanaszek","sequence":"additional","affiliation":[{"name":"NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8412-995X","authenticated-orcid":false,"given":"Malgorzata","family":"Ziemka-Nalecz","sequence":"additional","affiliation":[{"name":"NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1113\/JP272134","article-title":"Microglia across the Lifespan: From Origin to Function in Brain Development, Plasticity and Cognition","volume":"595","author":"Tay","year":"2017","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrneurol.2015.13","article-title":"The Role of Inflammation in Perinatal Brain Injury","volume":"11","author":"Hagberg","year":"2015","journal-title":"Nat. Rev. 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