Peptidome Analysis of Cerebrospinal Fluid in Neonates with Hypoxic-Ischemic Brain Damage

Abstract

Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. 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 = 4) or controls (n = 4). ITRAQ LC-MS/MS was used to identify differentially expressed peptides between two groups. Effects of the peptide from heat shock protein 90-alpha (HSP90α/HSP90AA1) on cell viability and pyroptosis under oxygen and glucose deprivation (OGD) were analyzed using cell counting kit-8 (CCK-8) assay and Annexin V-fluorescein isothiocyanate (FITC) Assay. Expressions of NLRP3, ASC and Caspase-1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Compared with the control group, one peptide significantly up-regulated and thirty-four peptides significantly down-regulated in the CSF of neonates with HIBD. A fragment of HSP90α/HSP90AA1 is the 2671.5 Da peptide (HSQFIGYPITLFVEKER), one of the down-regulated peptides in neonatal HIBD. This peptide, we named it HIBDAP, inhibited pyroptosis of PC12 cells under OGD by suppressing expressions of NLRP3, ASC and Caspase-1. 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 may provide new therapeutic targets for neonatal HIBD.

Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

“…us, a pyroptosis inhibitor was applied to rats with HIE, and its ability to alleviate injury severity was confirmed [30]. It was also demonstrated that the level of the HSP90α/HSP90AA1 peptide in the cerebrospinal fluid (CSF) of neonates with hypoxic-ischemic brain damage (HIBD) was reduced by peptidome analysis, and this peptide was involved in the NOD-LIKE receptor (NLR) signaling pathway [28]. Briefly, NLRP3-activated apoptosis plays a critical role in the pathophysiology of CP induced by HI and leads to brain damage [30].…”

“…NLRP3 inflammasome activation and pyroptosis have been described in neonatal hypoxic-ischemic encephalopathy [28][29][30][31]. When danger signals (such as ischemia and hypoxia) appear, NLRP3, an intracellular sensor, is able to recognize these signals and forms and activates the NLRP3 inflammasome [32].…”

Neuroprotective effect of a novel brain-derived peptide, HIBDAP, against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells

“…Compared to traditional drugs, peptide drugs have several bene cial properties such as less toxicity, accumulation in tissue and drug-drug interactions, and high biological and structural diversity [6]. Our previous study has shown that a 2671.5Da peptide (HSQFIGYPITLFVEKER) was decreased in the cerebrospinal uid of neonatal HIBD and we named it Hypoxic-Ischemic Brain Damage Associated Peptide (HIBDAP) [7].…”