{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:42:05Z","timestamp":1769557325922,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["2017\/27\/B\/NZ3\/00582"],"award-info":[{"award-number":["2017\/27\/B\/NZ3\/00582"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The histone deacetylase inhibitor (HDACi) Givinostat\/ITF2357 provides neuroprotection in adult models of brain injury; however, its action after neonatal hypoxia-ischemia (HI) is still undefined. The aim of our study was to test the hypothesis that the mechanism of Givinostat is associated with the alleviation of inflammation. For this purpose, we analyzed the microglial response and the effect on molecular mediators (chemokines\/cytokines) that are crucial for inducing cerebral damage after neonatal hypoxia-ischemia. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 60 min of hypoxia (7.6% O2). Givinostat (10 mg\/kg b\/w) was administered in a 5-day regimen. The effects of Givinostat on HI-induced inflammation (cytokine, chemokine and microglial activation and polarization) were assessed with a Luminex assay, immunohistochemistry and Western blot. Givinostat treatment did not modulate the microglial response specific for HI injury. After Givinostat administration, the investigated chemokines and cytokines remained at the level induced by HI. The only immunosuppressive effect of Givinostat may be associated with the decrease in MIP-1\u03b1. Neonatal hypoxia-ischemia produces an inflammatory response by activating the proinflammatory M1 phenotype of microglia, disrupting the microglia\u2013neuron (CX3CL1\/CX3CR1) axis and elevating numerous proinflammatory cytokines\/chemokines. Givinostat\/ITF2357 did not prevent an inflammatory reaction after HI.<\/jats:p>","DOI":"10.3390\/ijms23158287","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:11:05Z","timestamp":1658956265000},"page":"8287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of Givinostat\/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage"],"prefix":"10.3390","volume":"23","author":[{"given":"Paulina","family":"Pawelec","sequence":"first","affiliation":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences, 5, A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Sypecka","sequence":"additional","affiliation":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences, 5, A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-9495","authenticated-orcid":false,"given":"Teresa","family":"Zalewska","sequence":"additional","affiliation":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences, 5, A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Ziemka-Nalecz","sequence":"additional","affiliation":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences, 5, A. Pawinskiego Str., 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","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. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/aps.2013.89","article-title":"Inflammatory Responses in Hypoxic Ischemic Encephalopathy","volume":"34","author":"Liu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00431-021-04320-8","article-title":"New Possibilities for Neuroprotection in Neonatal Hypoxic-Ischemic Encephalopathy","volume":"181","author":"Victor","year":"2022","journal-title":"Eur. J. 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