Amantea Diana, Greco Rosaria, Micieli Giuseppe, Bagetta Giacinto
Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy.
Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.
Front Neurosci. 2018 Apr 10;12:241. doi: 10.3389/fnins.2018.00241. eCollection 2018.
The treatment of acute ischemic stroke is still an unresolved clinical problem since the only approved therapeutic intervention relies on early blood flow restoration through pharmacological thrombolysis, mechanical thrombus removal, or a combination of both strategies. Due to their numerous complications and to the narrow time-window for the intervention, only a minority of stroke patients can actually benefit from revascularization procedures, highlighting the urgent need of identifying novel strategies to prevent the progression of an irreversible damage in the ischemic penumbra. During the past three decades, the attempts to target the pathways implicated in the ischemic cascade (e.g., excitotoxicity, calcium channels overactivation, reactive oxygen species (ROS) production) have failed in the clinical setting. Based on a better understanding of the pathobiological mechanisms and on a critical reappraisal of most failed trials, numerous findings from animal studies have demonstrated that targeting the immune system may represent a promising approach to achieve neuroprotection in stroke. In particular, given the dualistic role of distinct components of both the innate and adaptive arms of the immune system, a strategic intervention should be aimed at establishing the right equilibrium between inflammatory and reparative mechanisms, taking into consideration their spatio-temporal recruitment after the ischemic insult. Thus, the application of immunomodulatory drugs and their ability to ameliorate outcomes deserve validation in patients with acute ischemic stroke.
急性缺血性中风的治疗仍然是一个尚未解决的临床问题，因为唯一被批准的治疗干预措施依赖于通过药物溶栓、机械取栓或两者结合的策略来早期恢复血流。由于这些治疗方法存在诸多并发症，且干预的时间窗较窄，实际上只有少数中风患者能够从血管再通手术中获益，这凸显了迫切需要确定新的策略来防止缺血半暗带中不可逆损伤的进展。在过去三十年中，针对缺血级联反应中涉及的途径（如兴奋性毒性、钙通道过度激活、活性氧（ROS）产生）的尝试在临床环境中均告失败。基于对病理生物学机制的更好理解以及对大多数失败试验的批判性重新评估，动物研究的大量发现表明，针对免疫系统可能是在中风中实现神经保护的一种有前景的方法。特别是，鉴于免疫系统固有和适应性分支的不同组成部分具有双重作用，战略干预应旨在在炎症和修复机制之间建立正确的平衡，同时考虑到缺血性损伤后它们在时空上的募集情况。因此，免疫调节药物的应用及其改善预后的能力值得在急性缺血性中风患者中进行验证。
