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One of the key pathogenic factors in hypoxic-ischemic (HI) brain injury is the inflammatory reaction including complement system activation. Over-activated complement stimulates cells to release inflammatory molecules and is involved in the post-ischemic degradation of synaptic connections. On the other hand, complement is also involved in regenerative processes. The histone deacetylase inhibitor (HDACi)\u2014sodium butyrate (SB)\u2014provides reduction of inflammation by decreasing the expression of the proinflammatory factors. The main purpose of this study was to examine the effect of SB treatment on complement activation and synapse elimination after HI. Neonatal HI was induced in Wistar rats pups by unilateral ligation of the common carotid artery followed by 60-min hypoxia (7.6% O2). SB (300\u00a0mg\/kg) was administered on a 5-day regimen. Our study has shown decreased levels of synapsin I, synaptophysin, and PSD-95 in the hypoxic-ischemic hemisphere, indicating synaptic loss after neonatal HI. Transmission electron microscopy revealed injury of the synaptic structures in the brain after HI. SB treatment increased the level of the synaptic proteins, improved tissue ultrastructure, and reduced degradation of the synapses. Neonatal HI induced mRNA expression of the complement C1q, C3, C5, and C9, and their receptors C3aR and C5aR. The effect of SB was different depending on the time after induction of hypoxic-ischemic damage. Our study demonstrated that neuroprotective effect of SB may be related to the modulation of complement activity after HI brain injury.<\/jats:p>","DOI":"10.1007\/s12035-024-04591-w","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T04:09:43Z","timestamp":1731384583000},"page":"5216-5233","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Impact of the Histone Deacetylase Inhibitor\u2014Sodium Butyrate on Complement-Mediated Synapse Loss in a Rat Model of Neonatal Hypoxia\u2013Ischemia"],"prefix":"10.1007","volume":"62","author":[{"given":"Karolina","family":"Ziabska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Gewartowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Frontczak-Baniewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sypecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8412-995X","authenticated-orcid":false,"given":"Malgorzata","family":"Ziemka-Nalecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"4591_CR1","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/S0140-6736(05)71048-5","volume":"365","author":"JE Lawn","year":"2005","unstructured":"Lawn JE, Cousens S, Zupan J (2005) 4 million neonatal deaths: when? 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