title: Recombinant T cell receptor ligand treatment improves neurological outcome in the presence of tissue plasminogen activator in experimental ischemic stroke.
abstract: RTL1000 is a partial human MHC molecule coupled to a human myelin peptide. We previously demonstrated that RTL1000 was protective against experimental ischemic stroke in HLA-DR2 transgenic (DR2-Tg) mice. Since thrombolysis with recombinant tissue plasminogen activator (t-PA) is a standard therapy for stroke, we determined if RTL1000 efficacy is altered when combined with t-PA in experimental stroke. Male DR2-Tg mice underwent 60 min of intraluminal middle cerebral artery occlusion (MCAO). t-PA or vehicle was infused intravenously followed by either a single or four daily subcutaneous injections of RTL1000 or vehicle. Infarct size was measured by 2, 3, 5-triphenyltetrazolium chloride staining at 24 or 96 h of reperfusion. Our data showed that t-PA alone reduced infarct size when measured at 24 h but not at 96 h after MCAO. RTL1000 alone reduced infarct size both at 24 and 96 h after MCAO. Combining RTL1000 with t-PA did not alter its ability to reduce infarct size at either 24 or 96 h after MCAO and provides additional protection in t-PA treated mice at 24 h after ischemic stroke. Taken together, RTL1000 treatment alone improves outcome and provides additional protection in t-PA-treated mice in experimental ischemic stroke.
authors: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, 97239, USA.
authors: Wenbin
authors: W
authors: Zhu
authors: Nicole L
authors: NL
authors: Libal
authors: Amanda
authors: A
authors: Casper
authors: Sheetal
authors: S
authors: Bodhankar
authors: Halina
authors: H
authors: Offner
authors: Nabil J
authors: NJ
authors: Alkayed
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; C542328:RTL1000 protein; D011993:Recombinant Fusion Proteins; D010959:Tissue Plasminogen Activator