Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA,
Transl Stroke Res. 2011 Sep;2(3):328-38. doi: 10.1007/s12975-011-0075-3. Epub 2011 Apr 3.
The majority of promising experimental compounds have failed in clinical trials, highlighting the need for novel approaches to treat stroke. Much research has been devoted to elucidating the signaling pathways involved in delayed neuroinflammation that can be targeted at clinically relevant time points. The field of stroke research has benefited from experiments characterizing the temporal expression profiles of candidate cytokines, chemokines, matrix metalloproteinases, and other putative pro-inflammatory molecules. Yet, these data have offered only a glimpse into the complex pathological sequelae and have not advanced the treatment of neuropathies. Upon recognition that peripheral immune cell activation is involved in penumbral expansion, the spleen has emerged as a novel target that mediates the peripheral immune response and promotes pro-inflammatory injury. Although the precise mechanisms have yet to be elucidated, accumulated evidence demonstrates that focal cerebral ischemia alters cytokine, chemokine, and immune cell profiles in the spleen. Additionally, removal of this peripheral lymphoid organ is neuroprotective, and the efficacy of several protective therapies has been linked to actions at the level of the spleen. Future experiments aimed at identifying the splenic lymphocyte populations that respond to ischemic stroke, as well as their signaling mechanisms, are critical in developing novel therapies.
大多数有前景的实验化合物在临床试验中都失败了，这突出表明需要新的方法来治疗中风。许多研究致力于阐明延迟性神经炎症中涉及的信号通路，这些信号通路可以在临床相关的时间点进行靶向治疗。中风研究领域得益于对候选细胞因子、趋化因子、基质金属蛋白酶和其他潜在促炎分子的时程表达谱进行的实验。然而，这些数据只是对复杂的病理后果有了初步了解，并没有推进神经病变的治疗。外周免疫细胞激活与半影区扩张有关的认识提出，脾脏作为一种新的靶点，介导外周免疫反应并促进促炎损伤。尽管确切的机制尚未阐明，但越来越多的证据表明，局灶性脑缺血改变了脾脏中的细胞因子、趋化因子和免疫细胞谱。此外，去除这个外周淋巴器官具有神经保护作用，几种保护疗法的疗效与脾脏水平的作用有关。未来旨在确定对缺血性中风有反应的脾淋巴细胞群体及其信号机制的实验对于开发新疗法至关重要。
