NDLI: Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke

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Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke

Content Provider	Springer Nature Link
Author	Zhu, Wenbin Casper, Amanda Libal, Nicole L. Murphy, Stephanie J. Bodhankar, Sheetal Offner, Halina Alkayed, Nabil J.
Copyright Year	2014
Abstract	Recombinant T cell Receptor Ligand 1000 (RTL1000), a partial human major histocompatibility complex (MHC) molecule coupled to a human myelin peptide, reduces infarct size after experimental stroke in HLA-DRB1*1502 transgenic (DR2-Tg) mice. In this study, we characterized the therapeutic time window of opportunity for RTL1000; we explored the efficacy of a single dose of RTL1000 administration and determined if RTL1000 affords long-term neurobehavioral functional improvement after ischemic stroke. Male DR2-Tg mice underwent 60 min of intraluminal reversible middle cerebral artery occlusion (MCAO). RTL1000 or vehicle was injected 4, 6, or 8 h after MCAO, followed by three daily injections. In the single-dose study, one-time injection of RTL1000 was applied 4 h after MCAO. Cortical, striatal, and hemispheric infarct sizes were measured 24 or 96 h after stroke. Behavioral testing, including neuroscore evaluation, open field, paw preference, and novel object recognition, was performed up to 28 days after stroke. Our data showed that RTL1000 significantly reduced the infarct size 96 h after MCAO when the first injection was given at 4 and 6 h, but not 8 h, after the onset of stroke. A single dose of 400 or 100 μg RTL1000 also significantly reduced the infarct size 24 h after MCAO. Behavioral testing showed that RTL1000 treatment used 4 h after MCAO improved long-term cognitive outcome 28 days after stroke. Taken together, RTL1000 protects against acute injury if applied within a 6-h time window and improves long-term functional recovery after experimental stroke in DR2-Tg mice.
Starting Page	60
Ending Page	68
Page Count	9
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	6
Issue Number	1
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2014-10-02
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ischemic stroke Neurobehavioral evaluation Immunotherapy Recombinant T cell receptor ligand HLA-DR2 transgenic mice Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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