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A New NF-κB Inhibitor, MEDS-23, Reduces the Severity of Adverse Post-Ischemic Stroke Outcomes in Rats

Authors :
Elina Rubin
Agnese C. Pippione
Matthew Boyko
Giacomo Einaudi
Stefano Sainas
Massimo Collino
Carlo Cifani
Marco L. Lolli
Naim Abu-Freha
Jacob Kaplanski
Donatella Boschi
Abed N. Azab
Source :
Brain Sciences, Vol 12, Iss 1, p 35 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Aim: Nuclear factor kappa B (NF-κB) is known to play an important role in the inflammatory process which takes place after ischemic stroke. The major objective of the present study was to examine the effects of MEDS-23, a potent inhibitor of NF-κB, on clinical outcomes and brain inflammatory markers in post-ischemic stroke rats. Main methods: Initially, a Toxicity Experiment was performed to determine the appropriate dose of MEDS-23 for use in animals, as MEDS-23 was analyzed in vivo for the first time. We used the middle cerebral artery occlusion (MCAO) model for inducing ischemic stroke in rats. The effects of MEDS-23 (at 10 mg/kg, ip) on post-stroke outcomes (brain inflammation, fever, neurological deficits, mortality, and depression- and anxiety-like behaviours) was tested in several efficacy experiments. Key findings: MEDS-23 was found to be safe and significantly reduced the severity of some adverse post-stroke outcomes such as fever and neurological deficits. Moreover, MEDS-23 significantly decreased prostaglandin E2 levels in the hypothalamus and hippocampus of post-stroke rats, but did not prominently alter the levels of interleukin-6 and tumor necrosis factor-α. Significance: These results suggest that NF-κB inhibition is a potential therapeutic strategy for the treatment of ischemic stroke.

Details

Language :
English
ISSN :
20763425
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Brain Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.620830c9d1f540aeba0455c3517c6158
Document Type :
article
Full Text :
https://doi.org/10.3390/brainsci12010035