title: Recombinant T cell receptor ligands improve outcome after experimental cerebral ischemia.
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.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Kozaburo
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Suzan
authors.initials: S
authors.lastname: Dziennis
authors.forename: Julie
authors.initials: J
authors.lastname: Palmateer
authors.forename: Xuefang
authors.initials: X
authors.lastname: Ren
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.forename: Paco S
authors.initials: PS
authors.lastname: Herson
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Hurn