PXD045168

PXD045168 is an original dataset announced via ProteomeXchange.

Title	Sildenafil Combined with Controlled Hypothermia Mitigates Microglial Activation After Neonatal Hypoxia-Ischemia in Rat.
Description	The only validated treatment to prevent brain damage associated with hypoxia-ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective drug candidates include sildenafil citrate, a phosphodiesterase-type 5 inhibitor. The main objective of this preclinical study is to assess its ability to reduce HI-induced neuroinflammation, in particular through its potential effect on microglial activation. HI was induced in P10 Sprague–Dawley rats by unilateral carotid permanent artery occlusion and hypoxia (HI), and treated by either hypothermia (HT) alone, Sildenafil (Sild) alone or combined treatment (SildHT). Lesion size, glial activation were analyzed by immunohistochemistry, qRT-PCR and proteomic analyses performed at P13. Exposure to any treatment was not associated with significant reduction in lesions size both in cerebral cortex and hippocampus, 72h after HI. Significant reductions in either Iba1+ (within the ipsilateral hemisphere) or GFAP+ cells (within the ipsilateral hippocampus) were observed in SildHT group, but not in the other treatment groups. In microglia sorted cells, pro-inflammatory markers, ie. Il1b, Il6, Nos2, and CD86 were significantly downregulated in SildHT treatment group only. These changes were restricted to ipsilateral hemisphere, were not evidenced in sorted astrocytes, and were not sex-dependent. Proteomic analyses in sorted microglia refined the pro-inflammatory effect of HI and confirmed a biologically relevant impact of SildHT on specific molecular pathways including notably genes related to neutrophilic functions. Our findings demonstrate that Sildenafil combined with controlled hypothermia confers maximum effect to mitigate microglial activation induced by HI through complex proteomic regulation. The reduction of neuroinflammation induced by Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.
HostingRepository	PRIDE
AnnounceDate	2024-04-30
AnnouncementXML	Submission_2024-04-30_07:06:47.419.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marjorie Leduc
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-06 13:22:07	ID requested
⏵ 1	2024-04-30 07:06:47	announced

10.1186/S12974-024-03022-W;

submitter keyword: Label free,Hypoxia-Ischemia, DIA, microglia

Olivier Baud
contact affiliation	Inserm UMR1141 NeuroDiderot, Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France. Laboratory of Child Growth and Development, University of Geneva, Geneva, Switzerland. Division of Neonatology and Pediatric Intensive Care, Children's University Hospital of Geneva, Geneva, Switzerland.
contact email	olivier.baud@hcuge.ch
lab head
Marjorie Leduc
contact affiliation	Plateforme protéomique 3P5, Université de Paris, Institut Cochin, INSERM, CNRS,
contact email	marjorie.leduc@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045168
     1. Label: PRIDE project
     2. Name: Sildenafil Combined with Controlled Hypothermia Mitigates Microglial Activation After Neonatal Hypoxia-Ischemia in Rat.