TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice

Melanie D. King, Cargill H. Alleyne, Krishnan M. Dhandapani

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

•R-7050, a novel TNFR antagonist, reduces neurovascular injury after ICH.•Pharmacological inhibition of TNFR improves outcomes after ICH.•TNFR may represent a viable therapeutic target after ICH. Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, exhibits the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, treatment options for ICH are lacking due in part to a lack of feasible therapeutic targets. Inflammatory activation is associated with neurological deficits in pre-clinical ICH models and with patient deterioration after clinical ICH. In the present study, we tested the hypothesis that R-7050, a novel cell permeable triazoloquinoxaline inhibitor of the tumor necrosis factor receptor (TNFR) complex, attenuates neurovascular injury after ICH in mice. Up to 2. h post-injury administration of R-7050 significantly reduced blood-brain barrier opening and attenuated edema development at 24. h post-ICH. Neurological outcomes were also improved over the first 3 days after injury. In contrast, R-7050 did not reduce hematoma volume, suggesting the beneficial effects of TNFR inhibition were downstream of clot formation/resolution. These data suggest a potential clinical utility for TNFR antagonists as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

Original languageEnglish (US)
Pages (from-to)92-96
Number of pages5
JournalNeuroscience Letters
Volume542
DOIs
StatePublished - May 10 2013

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Keywords

  • BBB
  • Blood-brain barrier
  • Edema
  • Hemorrhage
  • ICH
  • Inflammation
  • RIP1
  • Stroke
  • TNF-α
  • TNFR
  • TRADD
  • TRAF

ASJC Scopus subject areas

  • Neuroscience(all)

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