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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article number35
Number of pages16
JournalBrain Sciences
Volume12
Issue number1
DOIs
StatePublished - 1 Jan 2022

Keywords

  • Depression
  • Inflammation
  • Ischemic stroke
  • Mortality
  • NF-κB
  • Stroke

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