Recombinant T Cell Receptor Ligands Improve Outcome After Experimental Cerebral Ischemia

Kozaburo Akiyoshi, Suzan Dziennis, Julie Palmateer, Xuefang Ren, Arthur A. Vandenbark, Halina Offner, Paco S. Herson, Patricia D. Hurn

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A key target for novel stroke therapy is the regulation of post-ischemic inflammatory mechanisms. Recent evidence emphasizes the role of T lymphocytes of differing subtypes in the evolution is ischemic brain damage. We have recently demonstrated the benefit of myelin antigen-specific immunodulatory agents known as recombinant T cell receptor ligands (RTLs) in a standard murine model of focal stroke. The aim of the current study was to extend this initial observation to RTL treatment in a therapeutically relevant timing after middle cerebral artery occlusion (MCAO) and verify functional benefit to complement histological outcome measures. We observed that the administration of mouse-specific RTL551 reduced infarct size and improved sensorimotor outcome when administered within a 3 h post-ischemic therapeutic window. RTL551 treatment reduced cortical, caudate putamen, and total infarct volume as compared to vehicle-treated mice. Using a standard behavioral testing repertoire, we observed that RTL551 reduced sensorimotor impairment 3 days after MCAO. Humanized RTL1000 (HLA-DR2 moiety linked to hMOG-35-55 peptide) also reduced infarct size in HLA-DR2 transgenic mice. These data indicate that this neuroantigen-specific immunomodulatory agent reduces damage when administered in a therapeutically relevant reperfusion timeframe.

Original languageEnglish (US)
Pages (from-to)404-410
Number of pages7
JournalTranslational Stroke Research
Volume2
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Cerebral infarction
  • Cerebral ischemia
  • Immunotherapy
  • Inflammation
  • Middle cerebral artery occlusion
  • Mouse
  • Stroke
  • T lymphocyte

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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