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Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal HIBD. CSF samples were collected from neonates with HIBD (n\u2009=\u20094) or controls (n\u2009=\u20094). ITRAQ LC\u2013MS\/MS was used to identify differentially expressed peptides between two groups. A total of 35 differentially expressed peptides from 25 precursor proteins were identified. The 2671.5\u00a0Da peptide (HSQFIGYPITLFVEKER), one of the down-regulated peptides in neonatal HIBD, is a fragment of heat shock protein 90-alpha (HSP90\u03b1\/HSP90AA1). Results of bioinformatics analysis showed that HSP90\u03b1\/HSP90AA1 was located in the protein\u2013protein interaction (PPI) network hub and was involved in the NOD-LIKE receptor (NLR) signaling pathway. This peptide, we named it Hypoxic-Ischemic Brain Damage Associated Peptide (HIBDAP), is a hydrophilic peptide with high stability and has a long half-life of 3.5\u00a0h in mammalian reticulocytes. It was demonstrated that TAT-HIBDAP could successfully enter PC12 cells and further into the nucleus. After HIBDAP pretreatment and 6\u00a0h of OGD treatment, low concentrations of HIBDAP increased the survival rate of cells, except 40\u00a0\u03bcM had a toxic effect. Safe concentrations of HIBDAP reduced pyroptosis of PC12 cells under OGD, except 20\u00a0\u03bcM had no effect, by suppressing expressions of NLRP3, ASC and Caspase-1 except NLRP1. The results of our study identified the characterization and expression profiles of peptides in CSF of neonatal HIBD. Several meaningful peptides such as HIBDAP may play significant roles in neonatal HIBD and provide new therapeutic targets for neonatal HIBD.<\/jats:p>","DOI":"10.1186\/s13041-020-00671-9","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T06:02:58Z","timestamp":1601618578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Peptidome analysis of cerebrospinal fluid in neonates with hypoxic-ischemic brain damage"],"prefix":"10.1186","volume":"13","author":[{"given":"Xuewen","family":"Hou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-135X","authenticated-orcid":false,"given":"Jie","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"671_CR1","doi-asserted-by":"publisher","first-page":"22368","DOI":"10.3390\/ijms160922368","volume":"16","author":"BJ Dixon","year":"2015","unstructured":"Dixon BJ, Reis C, Ho WM, Tang J, Zhang JH. 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