Recombinant T Cell Receptor Ligands Improve Outcome After Experimental Cerebral Ischemia
Recombinant T Cell Receptor Ligands Improve Outcome After Experimental Cerebral Ischemia
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DOI：
10.1007/s12975-011-0085-1
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发表时间：
2011-09-01
影响因子：
6.9
通讯作者：
Hurn, Patricia D.
中科院分区：
文献类型：
--
作者：
Akiyoshi, Kozaburo;Dziennis, Suzan;Hurn, Patricia D.
新型卒中治疗的关键目标是调节缺血后炎症机制。最近的证据强调了不同亚型的T淋巴细胞在缺血性脑损伤演变中的作用。我们最近已经证明了髓鞘抗原特异性免疫调节剂的好处，称为重组T细胞受体配体（RTL）在标准的小鼠模型局灶性中风。本研究的目的是将这一初步观察结果扩展到大脑中动脉闭塞（MCAO）后治疗相关时间的RTL治疗，并验证功能获益，以补充组织学结局指标。我们观察到，当在缺血后3小时的治疗窗内给药时，小鼠特异性RTL 551的给药减少了梗死面积并改善了感觉运动结果。与媒介物处理的小鼠相比，RTL 551处理减少了皮质、尾壳核和总梗塞体积。使用标准行为测试库，我们观察到RTL 551减少MCAO后3天的感觉运动障碍。人源化RTL 1000（HLA-DR 2部分连接到hMOG-35-55肽）也减少了HLA-DR 2转基因小鼠的梗死面积。这些数据表明，这种神经抗原特异性免疫调节剂在治疗相关的再灌注时间范围内给药时减少损伤。
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.