PXD014440

PXD014440 is an original dataset announced via ProteomeXchange.

Title	Data in support of administration of a soluble TNF inhibitor that reduces infarct volume after focal cerebral ischemia in mice
Description	Background: Tumor necrosis factor, which exists both as a soluble (solTNF) and a transmembrane (tmTNF) protein, plays an important role in post-stroke inflammation. The objective of the present study was to test the effect of topical versus intracerebroventricular administration of XPro1595 (a solTNF inhibitor) and etanercept (a solTNF and tmTNF inhibitor) compared to saline on output measures such as infarct volume and post-stroke inflammation in mice. Methods: Adult male C57BL/6 mice were treated topically (2.5 mg/ml/1µl/hr for 3 consecutive days) or intracerebroventricularly (1.25 mg/kg/0.5 ml, once) with saline, XPro1595, or etanercept immediately after permanent middle cerebral artery occlusion (pMCAO). Mice were allowed to survive 1 or 3 days. Infarct volume, microglial and leukocyte profiles, and inflammatory markers were evaluated. Results: We found that topical, and not intracerebroventricular, administration of XPro1595 reduced infarct volume at both 1 day and 3 days after pMCAO. Etanercept showed no effect. We observed no changes in microglial or leukocyte populations. XPro1595 increased gene expression of P2ry12 at 1 day and Trem2 at 1 and 3 days, while decreasing Cx3cr1 expression at 1 and 3 days after pMCAO, suggesting a change in microglial activation towards a phagocytic phenotype. Conclusions: Our data demonstrate that topical administration of XPro1595 for three consecutive days decreases infarct volumes after ischemic stroke, while modifying microglial activation and the inflammatory response post-stroke. This suggests that inhibitors of solTNF hold great promise for future neuroprotective treatment in ischemic stroke.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:13.045.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Allan Stensballe
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-01 01:40:14	ID requested
1	2019-11-11 17:06:05	announced
⏵ 2	2024-10-22 04:05:16	announced	2024-10-22: Updated project metadata.

10.3389/fnins.2019.00781;

Yli-Karjanmaa M, Clausen BH, Degn M, Novrup HG, Ellman DG, Toft-Jensen P, Szymkowski DE, Stensballe A, Meyer M, Brambilla R, Lambertsen KL, Topical Administration of a Soluble TNF Inhibitor Reduces Infarct Volume After Focal Cerebral Ischemia in Mice. Front Neurosci, 13():781(2019) [pubmed]

submitter keyword: microglial activation, cytokines, neuroprotection,Ischemic stroke, behavior

Allan Stensballe
contact affiliation	Laboratory for Medical Mass spectroemtry
contact email	as@hst.aau.dk
lab head
Allan Stensballe
contact affiliation	Aalborg University
contact email	as@hst.aau.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014440
     1. Label: PRIDE project
     2. Name: Data in support of administration of a soluble TNF inhibitor that reduces infarct volume after focal cerebral ischemia in mice