Spaulding Rehabilitation Hospital, Department of Physical Medicine and Rehabilitation, Boston, MA, USA.
Expert Opin Ther Targets. 2012 Oct;16(10):1013-25. doi: 10.1517/14728222.2012.715149. Epub 2012 Aug 27.
Stroke is the third leading cause of death and a major cause of long-term disability in the adult population. Growing evidence suggests that inflammation may play an important role in the evolution of stroke. Because Rho-associated coiled-coil containing kinases (ROCKs) are important mediators of inflammation, they may contribute to stroke and stroke recovery.
The pathophysiological role of ROCKs in mediating inflammation at different phases of stroke, and the therapeutic opportunities for stroke prevention and stroke treatment with ROCK inhibitors will be discussed.
Inflammation is a double-edged sword during the evolution of stroke. Immunomodulation might provide a novel therapeutic approach for stroke prevention and stroke treatment. ROCK plays an important role in mediating the inflammatory response following vascular injury as well as platelet activation and thrombus formation. ROCK inhibitors have been shown to be beneficial in stroke prevention, acute neuroprotection and chronic stroke recovery by affecting inflammatory-mediated platelet and endothelial function, smooth muscle contraction and neuronal regeneration. Thus, ROCK-mediated inflammation could be a potential therapeutic target for stroke prevention and stroke treatment. However, the mechanism by which ROCKs regulate the inflammatory response is unclear, and the role of the two ROCK isoforms in stroke and stroke recovery remains to be determined.
中风是成年人死亡的第三大原因,也是长期残疾的主要原因。越来越多的证据表明,炎症可能在中风的发展中起重要作用。由于 ROCK 激酶(ROCKs)是炎症的重要介质,因此它们可能导致中风及其恢复。
ROCK 在中风不同阶段介导炎症的病理生理学作用,以及 ROCK 抑制剂在中风预防和治疗中的治疗机会。
在中风的发展过程中,炎症是一把双刃剑。免疫调节可能为中风预防和治疗提供一种新的治疗方法。ROCK 在血管损伤后以及血小板激活和血栓形成过程中炎症反应的调节中起重要作用。ROCK 抑制剂已被证明通过影响炎症介导的血小板和内皮功能、平滑肌收缩和神经元再生,对中风预防、急性神经保护和慢性中风恢复有益。因此,ROCK 介导的炎症可能是中风预防和治疗的一个潜在治疗靶点。然而,ROCK 调节炎症反应的机制尚不清楚,两种 ROCK 同工型在中风和中风恢复中的作用仍有待确定。