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

Wenbin Zhu, Amanda Casper, Nicole L. Libal, Stephanie J. Murphy, Sheetal Bodhankar, Halina Offner, Nabil Alkayed

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)60-68
Number of pages9
JournalTranslational Stroke Research
Volume6
Issue number1
DOIs
StatePublished - 2014

Fingerprint

T-Cell Antigen Receptor
Stroke
Ligands
Middle Cerebral Artery Infarction
Transgenic Mice
Therapeutics
Injections
Corpus Striatum
HLA-DRB1 Chains
Myelin Sheath
Major Histocompatibility Complex
Peptides
Wounds and Injuries

Keywords

  • HLA-DR2 transgenic mice
  • Immunotherapy
  • Ischemic stroke
  • Neurobehavioral evaluation
  • Recombinant T cell receptor ligand

ASJC Scopus subject areas

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

Cite this

Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke. / Zhu, Wenbin; Casper, Amanda; Libal, Nicole L.; Murphy, Stephanie J.; Bodhankar, Sheetal; Offner, Halina; Alkayed, Nabil.

In: Translational Stroke Research, Vol. 6, No. 1, 2014, p. 60-68.

Research output: Contribution to journalArticle

Zhu, Wenbin ; Casper, Amanda ; Libal, Nicole L. ; Murphy, Stephanie J. ; Bodhankar, Sheetal ; Offner, Halina ; Alkayed, Nabil. / Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke. In: Translational Stroke Research. 2014 ; Vol. 6, No. 1. pp. 60-68.
@article{754970ea1f134aa28d60fb36cbade416,
title = "Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke",
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.",
keywords = "HLA-DR2 transgenic mice, Immunotherapy, Ischemic stroke, Neurobehavioral evaluation, Recombinant T cell receptor ligand",
author = "Wenbin Zhu and Amanda Casper and Libal, {Nicole L.} and Murphy, {Stephanie J.} and Sheetal Bodhankar and Halina Offner and Nabil Alkayed",
year = "2014",
doi = "10.1007/s12975-014-0373-7",
language = "English (US)",
volume = "6",
pages = "60--68",
journal = "Translational Stroke Research",
issn = "1868-4483",
publisher = "Springer US",
number = "1",

}

TY - JOUR

T1 - Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as a Therapeutic Agent in Ischemic Stroke

AU - Zhu, Wenbin

AU - Casper, Amanda

AU - Libal, Nicole L.

AU - Murphy, Stephanie J.

AU - Bodhankar, Sheetal

AU - Offner, Halina

AU - Alkayed, Nabil

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - HLA-DR2 transgenic mice

KW - Immunotherapy

KW - Ischemic stroke

KW - Neurobehavioral evaluation

KW - Recombinant T cell receptor ligand

UR - http://www.scopus.com/inward/record.url?scp=84921053967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921053967&partnerID=8YFLogxK

U2 - 10.1007/s12975-014-0373-7

DO - 10.1007/s12975-014-0373-7

M3 - Article

C2 - 25270354

AN - SCOPUS:84921053967

VL - 6

SP - 60

EP - 68

JO - Translational Stroke Research

JF - Translational Stroke Research

SN - 1868-4483

IS - 1

ER -