Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
Transl Stroke Res. 2011 Sep 1;2(3):404-10. doi: 10.1007/s12975-011-0085-1.
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.
新型中风治疗的一个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 T 淋巴细胞在缺血性脑损伤演变中的作用。我们最近在局灶性中风的标准小鼠模型中证明了髓鞘抗原特异性免疫调节药物（称为重组 T 细胞受体配体 [RTL]）的益处。本研究的目的是将这一初步观察结果扩展到 MCAO 后治疗相关时间的 RTL 治疗，并验证功能益处以补充组织学结果测量。我们观察到，在 3 小时的缺血后治疗窗口内给予小鼠特异性 RTL551 可减少梗死面积并改善感觉运动功能。与载体处理的小鼠相比，RTL551 处理减少了皮质、尾状核和总梗死体积。使用标准行为测试谱，我们观察到 RTL551 可降低 MCAO 后 3 天的感觉运动障碍。人源化 RTL1000（与 hMOG-35-55 肽连接的 HLA-DR2 部分）也减少了 HLA-DR2 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再灌注时间范围内给药时可减少损伤。
